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Alzu'bi A, Abu-El-Rub E, Al-Trad B, Alzoubi H, Abu-El-Rub H, Albals D, Abdelhady GT, Bader NS, Almazari R, Al-Zoubi RM. In vivo assessment of the nephrotoxic effects of the synthetic cannabinoid AB-FUBINACA. Forensic Toxicol 2025; 43:86-96. [PMID: 39120650 PMCID: PMC11782324 DOI: 10.1007/s11419-024-00699-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 07/28/2024] [Indexed: 08/10/2024]
Abstract
BACKGROUND The widespread misuse of synthetic cannabinoids (SCs) has led to a notable increase in reported adverse effects, raising significant health concerns. SCs use has been particularly associated with acute kidney injury (AKI). However, the pathogenesis of SCs-induced AKI is not well-understood. METHODS We investigated the nephrotoxic effect of acute administration of N-[(1S)- 1-(aminocarbonyl)-2-methylpropyl]-1-[(4-fluorophenyl)methyl]-1H-indazole-3-carboxamide (AB-FUBINKA) (3 mg/kg for 5 days) in mice. Various parameters of oxidative stress, inflammation, and apoptosis have been quantified. The expressions of mitochondrial complexes (I-V) in renal tissues were also assessed. RESULTS Our findings showed that AB-FUBINACA induced substantial impairment in the renal function that is accompanied by elevated expression of renal tubular damage markers; KIM-1 and NGAL. Administration of AB-FUBINACA was found to be associated with a significant increase in the expression of oxidative stress markers (iNOS, NOX4, NOX2, NOS3) and the level of lipid peroxidation in the kidney. The expression of pro-inflammatory markers (IL-6, TNF-alpha, NF-kB) was also enhanced following exposure to AB-FUBINACA. These findings were also correlated with increased expression of major apoptosis regulatory markers (Bax, caspase-9, caspase-3) and reduced expression of mitochondrial complexes I, III, and IV. CONCLUSION These results indicate that AB-FUBINACA can trigger oxidative stress and inflammation, and activate caspase-dependent apoptosis in the kidney, with these processes being possibly linked to disruption of mitochondrial complexes and could be an underlying mechanism of SCs-induced nephrotoxicity.
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Affiliation(s)
- Ayman Alzu'bi
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, 211-63, Jordan.
| | - Ejlal Abu-El-Rub
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, 211-63, Jordan
| | - Bahaa Al-Trad
- Department of Biological Sciences, Faculty of Science, Yarmouk University, Irbid, 211-63, Jordan
| | - Hiba Alzoubi
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, 211-63, Jordan
| | - Hadeel Abu-El-Rub
- Department of Clinical Sciences, Faculty of Medicine, Yarmouk University, Irbid, 211-63, Jordan
| | - Dima Albals
- Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Yarmouk University, Irbid, 211-63, Jordan
| | - Gamal T Abdelhady
- Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, 11566, Egypt
| | - Noor S Bader
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, 211-63, Jordan
| | - Rawan Almazari
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, 211-63, Jordan
| | - Raed M Al-Zoubi
- Surgical Research Section, Department of Surgery, Hamad Medical Corporation, 3050, Doha, Qatar.
- Department of Biomedical Sciences, QU-Health, College of Health Sciences, Qatar University, 2713, Doha, Qatar.
- Department of Chemistry, Jordan University of Science and Technology, P.O.Box 3030, Irbid, 22110, Jordan.
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Jarocka-Karpowicz I, Dobrzyńska I, Stasiewicz A, Skrzydlewska E. 3-O-Ethyl Ascorbic Acid and Cannabigerol in Modulating the Phospholipid Metabolism of Keratinocytes. Antioxidants (Basel) 2024; 13:1285. [PMID: 39594427 PMCID: PMC11591156 DOI: 10.3390/antiox13111285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 10/19/2024] [Accepted: 10/22/2024] [Indexed: 11/28/2024] Open
Abstract
Phospholipids and their metabolites play an important role in maintaining the membrane integrity and the metabolic functions of keratinocytes under physiological conditions and in the regeneration process after exposure to high-energy UVB radiation. Therefore, in the search for compounds with a protective and regenerative effect on keratinocyte phospholipids, the effectiveness of two antioxidant compounds has been tested: a stable derivative of ascorbic acid, 3-O-ethyl ascorbic acid (EAA) and cannabigerol (CBG), both of which are primarily located in the membrane structures of keratinocytes. In addition, this study has demonstrated that EAA and CBG, especially in a two-component combination, enhance the antioxidant properties of keratinocytes and reduce lipid peroxidation assessed at the level of MDA (malondialdehyde)/neuroprostanes. Moreover, by reducing the activity of enzymes that metabolise phospholipids, free PUFAs (polyunsaturated fatty acids) and endocannabinoids (PLA2; phospholipase A2, COX1/2; cyclooxygenases 1/2, LOX-5; lipoxygenase 5, FAAH; fatty acid amide hydrolase, MAGL; monoacylglycerol lipase), antioxidants have been found to regulate the levels of endocannabinoids (AEA; anandamide, 2-AG; 2-arachidonoylglycerol, PEA; palmitoylethanolamide) and eicosanoids (PGD2; prostaglandin D2, PGE2; prostaglandin E2, 15-d-PGJ2; 15-deoxy-Δ12,14-prostaglandin J2, 15-HETE; 15-hydroxyeicosatetraenoic acid), that are enhanced by UVB radiation. The metabolic effect of both groups of PUFA metabolites is mainly related to the activation of G protein-related receptors (CB1/2; cannabinoid receptor 1 and 2, PPARγ; peroxisome proliferator-activated receptor gamma, TRPV1; transient receptor potential cation channel subfamily V member 1), the expression of which is reduced under the influence of EAA, CBG, and especially the two-component combination. It promotes the regeneration of keratinocyte metabolism disrupted by UVB, particularly in relation to redox balance and inflammation.
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Affiliation(s)
- Iwona Jarocka-Karpowicz
- Department of Analytical Chemistry, Medical University of Białystok, Mickiewicza 2D, 15-222 Białystok, Poland; (I.J.-K.); (A.S.)
| | - Izabela Dobrzyńska
- Laboratory of Bioanalysis, Faculty of Chemistry, University in Białystok, Ciołkowskiego 1K, 15-245 Białystok, Poland;
| | - Anna Stasiewicz
- Department of Analytical Chemistry, Medical University of Białystok, Mickiewicza 2D, 15-222 Białystok, Poland; (I.J.-K.); (A.S.)
| | - Elżbieta Skrzydlewska
- Department of Analytical Chemistry, Medical University of Białystok, Mickiewicza 2D, 15-222 Białystok, Poland; (I.J.-K.); (A.S.)
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Rouholamini FS, Aminaei M, Aminizadeh S. The effect of eight weeks of endurance training and MitoQ supplementation on antioxidant capacity and the expression of sestrin-2 and AMPK in cardiac tissue of aged rats. Exp Gerontol 2024; 196:112572. [PMID: 39233194 DOI: 10.1016/j.exger.2024.112572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 09/01/2024] [Accepted: 09/02/2024] [Indexed: 09/06/2024]
Abstract
PURPOSE The present study aimed to investigate the effects of endurance training (ET) in combination with MitoQ supplementation on antioxidant indices and the expression of sesterin-2 (SESN2) as an anti-aging factor and AMPK as an energy sensor in aged male Wistar rats. METHODS Twenty-eight aged Wistar rats (410 ± 15 g, 22 ± 1.5 months old) were randomly divided into four groups (n = 7): Control, ET (eight weeks endurance training on the treadmill), MitoQ (250 μ/L in drinking water), and ET + MitoQ. We measured the protein and gene expression of SESN2 and AMPK in the heart tissue by western blotting and real-time PCR, respectively. In addition, antioxidant indices, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activity, and oxidant malondialdehyde (MDA) concentration in the cardiac tissue and serum were measured. RESULTS SESN2 and AMPK protein expression significantly increased in the MitoQ group compared to the control group (P = 0.002, P = 0.0003). MDA content in tissue and serum remained unchanged in all groups (P > 0.05). MitoQ supplementation significantly increased SOD and GPx enzyme activity in serum and cardiac tissue (P = 0.001). CONCLUSION Overall, ET and MitoQ alone and in combination have anti-aging effects and improve the expression of AMPK and SESN2. Additionally, ET and MitoQ lead to improved antioxidant capacity in aged rats by ameliorating the activity of antioxidant enzymes.
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Affiliation(s)
- Fatemeh Sadat Rouholamini
- Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Shahid Bahonar University of Kerman, Kerman, Iran
| | - Mohsen Aminaei
- Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Shahid Bahonar University of Kerman, Kerman, Iran
| | - Soheil Aminizadeh
- Physiology Research Center, Institute of Neuropharmacology, Department of Physiology and Pharmacology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
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Fassarella LB, Neto JGO, Woyames J, Santos GRC, Pereira HMG, Pazos-Moura CC, Trevenzoli IH. Fish oil supplementation during pregnancy decreases liver endocannabinoid system and lipogenic markers in newborn rats exposed to maternal high-fat diet. Eur J Nutr 2024; 63:1565-1579. [PMID: 38727803 DOI: 10.1007/s00394-024-03422-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 02/09/2024] [Indexed: 08/18/2024]
Abstract
PURPOSE Maternal high-fat diet (HF) programs obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), hypertriglyceridemia, and hyperglycemia associated with increased endocannabinoid system (ECS) in the liver of adult male rat offspring. We hypothesized that maternal HF would induce sex specific ECS changes in the liver of newborn rats, prior to obesity onset, and maternal fish oil (FO) supplementation would reprogram the ECS and lipid metabolism markers preventing liver triglycerides (TG) accumulation. METHODS Female rats received a control (CT) (10.9% fat) or HF (28.7% fat) diet 8 weeks prior to mating and during pregnancy. A subgroup of HF dams received 3% FO supplementation in the HF diet (35.4% fat) during pregnancy (HFFO). Serum hormones and liver TG, ECS, lipid metabolism, oxidative stress and autophagy markers were assessed in male and female newborn offspring. RESULTS Maternal HF diet increased liver cannabinoid receptor 1 (CB1) in males and decreased CB2 in females, with no effect on liver TG. Maternal FO supplementation reduced liver CB1 regardless of the offspring sex, but reduced TG liver content only in females. FO reduced the liver content of the endocannabinoid anandamide in males, and the content of 2-arachidonoylglycerol in both sexes. Maternal HF increased lipogenic and decreased lipid oxidation markers, and FO induced the opposite regulation in the liver of offspring. CONCLUSION Prenatal HF and FO differentially modulate liver ECS in the offspring before obesity and MASLD development. These results suggest that maternal nutrition at critical stages of development can modulate the offspring's ECS, predisposing or preventing the onset of metabolic diseases.
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Affiliation(s)
- Larissa B Fassarella
- Laboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Rio de Janeiro, 21941-902, Brasil
| | - Jessika G O Neto
- Laboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Rio de Janeiro, 21941-902, Brasil
| | - Juliana Woyames
- Laboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Rio de Janeiro, 21941-902, Brasil
| | - Gustavo R C Santos
- Laboratório Brasileiro de Controle de Dopagem, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
| | - Henrique M G Pereira
- Laboratório Brasileiro de Controle de Dopagem, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
| | - Carmen C Pazos-Moura
- Laboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Rio de Janeiro, 21941-902, Brasil
| | - Isis H Trevenzoli
- Laboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Rio de Janeiro, 21941-902, Brasil.
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Kong X, Gao X, Wang W. Oxidative balance score and associations with dyslipidemia and mortality among US adults: A mortality follow-up study of a cross-sectional cohort. JPEN J Parenter Enteral Nutr 2024; 48:735-745. [PMID: 38922706 DOI: 10.1002/jpen.2661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 05/29/2024] [Accepted: 05/29/2024] [Indexed: 06/28/2024]
Abstract
BACKGROUND Oxidative stress has been implicated in the pathogenesis and progression of dyslipidemia. We aimed to investigate the association between the oxidative balance score, and dyslipidemia, as well as to assess the mortality risk associated with oxidative balance score in patients with dyslipidemia. METHODS We performed a mortality follow-up study of a cross-sectional cohort of 26,118 adults from the National Health and Nutrition Examination Survey 1999-2018. The total oxidative balance score was calculated by 16 dietary nutrients (dietary oxidative balance score) and four lifestyle factors (lifestyle oxidative balance score). Weighted Cox proportional hazard model was applied to determine the relationship between oxidative balance score and all-cause or cardiovascular disease (CVD) mortality within the dyslipidemia group. RESULTS During a median follow-up of 118 months, 2448 all-cause deaths (766 CVD-related) occurred. A significant negative correlation was observed between total oxidative balance score, dietary oxidative balance score, lifestyle oxidative balance score, and dyslipidemia. The multivariable-adjusted odds ratios and 95% CIs for dyslipidemia were 0.86 (0.77-0.97), 0.80 (0.72-0.91), and 0.63 (0.56-0.70), respectively, when comparing the second, third, and fourth quartiles of total oxidative balance score to the reference lowest quartile (P for trend <0.0001). Increasing total oxidative balance score was inversely associated with all-cause (hazard ratio [HR] = 0.98, 95% CI 0.98-0.99) and CVD-specific mortality (HR = 0.98, 95% CI 0.97-0.99) in participants with dyslipidemia. CONCLUSIONS Oxidative balance score is inversely associated with dyslipidemia and linked to all-cause and CVD-related mortality, highlighting the potentially protective role of an antioxidant-rich diet against dyslipidemia.
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Affiliation(s)
- Xiufang Kong
- Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xinghui Gao
- Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Wei Wang
- Department of Nephrology, Shanghai Tenth People's Hospital, Shanghai, China
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Jin S, Kang PM. A Systematic Review on Advances in Management of Oxidative Stress-Associated Cardiovascular Diseases. Antioxidants (Basel) 2024; 13:923. [PMID: 39199169 PMCID: PMC11351257 DOI: 10.3390/antiox13080923] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 07/10/2024] [Accepted: 07/19/2024] [Indexed: 09/01/2024] Open
Abstract
Oxidative stress plays a significant role in the pathogenesis of cardiovascular diseases, such as myocardial ischemia/reperfusion injury, atherosclerosis, heart failure, and hypertension. This systematic review aims to integrate most relevant studies on oxidative stress management in cardiovascular diseases. We searched relevant literatures in the PubMed database using specific keywords. We put emphasis on those manuscripts that were published more recently and in higher impact journals. We reviewed a total of 200 articles. We examined current oxidative stress managements in cardiovascular diseases, including supplements like resveratrol, vitamins C and E, omega-3 fatty acids, flavonoids, and coenzyme-10, which have shown antioxidative properties and potential cardiovascular benefits. In addition, we reviewed the pharmacological treatments including newly discovered antioxidants and nanoparticles that show potential effects in targeting the specific oxidative stress pathways. Lastly, we examined biomarkers, such as soluble transferrin receptor, transthyretin, and cystatin C in evaluating antioxidant status and identifying cardiovascular risk. By addressing oxidative stress management and mechanisms, this paper emphasizes the importance of maintaining the balance between oxidants and antioxidants in the progression of cardiovascular diseases. This review paper is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), registration # INPLASY202470064.
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Affiliation(s)
- Soyeon Jin
- Cardiovascular Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, 3 Blackfan Circle, CLS 910, Boston, MA 02215, USA
- School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences, Boston, MA 02115, USA
| | - Peter M. Kang
- Cardiovascular Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, 3 Blackfan Circle, CLS 910, Boston, MA 02215, USA
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Alzu'bi A, Abu-El-Rub E, Almahasneh F, Tahat L, Athamneh RY, Khasawneh R, Alzoubi H, Ghorab DS, Almazari R, Zoubi MSA, Al-Zoubi RM. Delineating the molecular mechanisms of hippocampal neurotoxicity induced by chronic administration of synthetic cannabinoid AB-FUBINACA in mice. Neurotoxicology 2024; 103:50-59. [PMID: 38823587 DOI: 10.1016/j.neuro.2024.05.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 05/28/2024] [Accepted: 05/28/2024] [Indexed: 06/03/2024]
Abstract
Chronic use of synthetic cannabinoids (SCs) has been associated with cognitive and behavioural deficits and an increased risk of neuropsychiatric disorders. The underlying molecular and cellular mechanisms of the neurotoxic effects of long-term use of SCs have not been well investigated in the literature. Herein, we evaluated the in vivo effects of chronic administration of AB-FUBINACA on the hippocampus in mice. Our results revealed that the administration of AB-FUBINACA induced a significant impairment in recognition memory associated with histopathological changes in the hippocampus. These findings were found to be correlated with increased level of oxidative stress, neuroinflammation, and apoptosis markers, and reduced expression of brain-derived neurotrophic factor (BDNF), which plays an essential role in modulating synaptic plasticity integral for promoting learning and memory in the hippocampus. Additionally, we showed that AB-FUBINACA significantly decreased the expression of NR1, an important functional subunit of glutamate/NMDA receptors and closely implicated in the development of toxic psychosis. These findings shed light on the long-term neurotoxic effects of SCs on hippocampus and the underlying mechanisms of these effects. This study provided new targets for possible medical interventions to improve the treatment guidelines for SCs addiction.
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Affiliation(s)
- Ayman Alzu'bi
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan.
| | - Ejlal Abu-El-Rub
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan
| | - Fatimah Almahasneh
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan
| | - Lena Tahat
- Department of Biological Sciences, Faculty of Science, Yarmouk University, Irbid 211-63, Jordan
| | - Rabaa Y Athamneh
- Department of Medical Laboratory Sciences, Faculty of Allied Science, Zarqa University, Zarqa 13110, Jordan
| | - Ramada Khasawneh
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan
| | - Hiba Alzoubi
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan
| | - Doaa S Ghorab
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan; Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Rawan Almazari
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan
| | - Mazhar Salim Al Zoubi
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan
| | - Raed M Al-Zoubi
- Surgical Research Section, Department of Surgery, Hamad Medical Corporation, Doha, Qatar; Department of Biomedical Sciences, QU-Health, College of Health Sciences, Qatar University, Doha 2713, Qatar; Department of Chemistry, Jordan University of Science and Technology, P.O.Box 3030, Irbid 22110, Jordan.
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Belali R, Mard SA, Khoshnam SE, Bavarsad K, Sarkaki A, Farbood Y. Anandamide Attenuates Neurobehavioral Deficits and EEG Irregularities in the Chronic Sleep Deprivation Rats: The Role of Oxidative Stress and Neuroinflammation. Neurochem Res 2024; 49:1541-1555. [PMID: 37966567 DOI: 10.1007/s11064-023-04054-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 10/10/2023] [Accepted: 10/20/2023] [Indexed: 11/16/2023]
Abstract
Sleep deprivation increases stress, anxiety, and depression by altering the endocannabinoid system's function. In the present study, we aimed to investigate the anti-anxiety and anti-depressant effects of the endocannabinoid anandamide (AEA) in the chronic sleep deprivation (SD) model in rats. Adult male Wistar rats (200-250 g) were randomly divided into three groups: control + vehicle (Control), chronic sleep deprivation + vehicle (SD), and chronic sleep deprivation + 20 mg/kg AEA (SD + A). The rats were kept in a sleep deprivation device for 18 h (7 to 1 a.m.) daily for 21 days. Open-field (OFT), elevated plus maze, and forced swimming tests (FST) were used to assess anxiety and depression-like behavior. As well as the cortical EEG, CB1R mRNA expression, TNF-α, IL-6, IL-4 levels, and antioxidant activity in the brain were examined following SD induction. AEA administration significantly increased the time spent (p < 0.01), the distance traveled in the central zone (p < 0.001), and the number of climbing (p < 0.05) in the OFT; it also increased the duration and number of entries into the open arms (p < 0.01 and p < 0.05 respectively), and did not reduce immobility time in the FST (p > 0.05), AEA increased CB1R mRNA expression in the anterior and medial parts of the brain (p < 0.01), and IL-4 levels (p < 0.05). AEA also reduced IL-6 and TNF-α (p < 0.05) and modulated cortical EEG. AEA induced anxiolytic-like effects but not anti-depressant effects in the SD model in rats by modulating CB1R mRNA expression, cortical EEG, and inflammatory response.
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Affiliation(s)
- Rafie Belali
- Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Persian Gulf Physiology Research Center, Basic Medical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Seyyed Ali Mard
- Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Persian Gulf Physiology Research Center, Basic Medical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Seyed Esmaeil Khoshnam
- Persian Gulf Physiology Research Center, Basic Medical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Kowsar Bavarsad
- Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Persian Gulf Physiology Research Center, Basic Medical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Alireza Sarkaki
- Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
- Persian Gulf Physiology Research Center, Basic Medical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Yaghoob Farbood
- Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
- Persian Gulf Physiology Research Center, Basic Medical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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Yang W, Schoeman JC, Di X, Lamont L, Harms AC, Hankemeier T. A comprehensive UHPLC-MS/MS method for metabolomics profiling of signaling lipids: Markers of oxidative stress, immunity and inflammation. Anal Chim Acta 2024; 1297:342348. [PMID: 38438234 DOI: 10.1016/j.aca.2024.342348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 01/30/2024] [Accepted: 02/04/2024] [Indexed: 03/06/2024]
Abstract
Signaling lipids (SLs) play a crucial role in various signaling pathways, featuring diverse lipid backbone structures. Emerging evidence showing the biological significance and biomedical values of SLs has strongly spurred the advancement of analytical approaches aimed at profiling SLs. Nevertheless, the dramatic differences in endogenous abundances across lipid classes as well as multiple isomers within the same lipid class makes the development of a generic analytical method challenging. A better analytical method that combines comprehensive coverage and high sensitivity is needed to enable us to gain a deeper understanding of the biochemistry of these molecules in health and disease. In this study, we developed a fast and comprehensive targeted ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for profiling SLs. The platform enables analyses of 260 metabolites covering oxylipins (isoprostanes, prostaglandins and other oxidized lipids), free fatty acids, lysophospholipids, sphingoid bases (C16, C18), platelet activating factors (C16, C18), endocannabinoids and bile acids. Various validation parameters including linearity, limit of detection, limit of quantification, extraction recovery, matrix effect, intra-day and inter-day precision were used to characterize this method. Metabolite quantitation was successfully achieved in both NIST Standard Reference Material for human plasma (NIST SRM 1950) and pooled human plasma, with 109 and 144 metabolites quantitated. The quantitation results in NIST SRM 1950 plasma demonstrated good correlations with certified or previously reported values in published literature. This study introduced quantitative data for 37 SLs for the first time. Metabolite concentrations measured in NIST SRM 1950 will serve as essential reference data for facilitating interlaboratory comparisons. The methodology established here will be the cornerstone for in-depth profiling of signaling lipids across diverse biological samples and contexts.
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Affiliation(s)
- Wei Yang
- Metabolomics and Analytics Center, Leiden Academic Centre of Drug Research, Leiden University, 2333 CC, Leiden, the Netherlands
| | - Johannes C Schoeman
- Metabolomics and Analytics Center, Leiden Academic Centre of Drug Research, Leiden University, 2333 CC, Leiden, the Netherlands
| | - Xinyu Di
- Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, 2333 CC, Leiden, the Netherlands
| | - Lieke Lamont
- Metabolomics and Analytics Center, Leiden Academic Centre of Drug Research, Leiden University, 2333 CC, Leiden, the Netherlands
| | - Amy C Harms
- Metabolomics and Analytics Center, Leiden Academic Centre of Drug Research, Leiden University, 2333 CC, Leiden, the Netherlands
| | - Thomas Hankemeier
- Metabolomics and Analytics Center, Leiden Academic Centre of Drug Research, Leiden University, 2333 CC, Leiden, the Netherlands.
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Kanwal H, Sangineto M, Ciarnelli M, Castaldo P, Villani R, Romano AD, Serviddio G, Cassano T. Potential Therapeutic Targets to Modulate the Endocannabinoid System in Alzheimer's Disease. Int J Mol Sci 2024; 25:4050. [PMID: 38612861 PMCID: PMC11012768 DOI: 10.3390/ijms25074050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 03/22/2024] [Accepted: 03/25/2024] [Indexed: 04/14/2024] Open
Abstract
Alzheimer's disease (AD), the most common neurodegenerative disease (NDD), is characterized by chronic neuronal cell death through progressive loss of cognitive function. Amyloid beta (Aβ) deposition, neuroinflammation, oxidative stress, and hyperphosphorylated tau proteins are considered the hallmarks of AD pathology. Different therapeutic approaches approved by the Food and Drug Administration can only target a single altered pathway instead of various mechanisms that are involved in AD pathology, resulting in limited symptomatic relief and almost no effect in slowing down the disease progression. Growing evidence on modulating the components of the endocannabinoid system (ECS) proclaimed their neuroprotective effects by reducing neurochemical alterations and preventing cellular dysfunction. Recent studies on AD mouse models have reported that the inhibitors of the fatty acid amide hydrolase (FAAH) and monoacylglycerol (MAGL), hydrolytic enzymes for N-arachidonoyl ethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), respectively, might be promising candidates as therapeutical intervention. The FAAH and MAGL inhibitors alone or in combination seem to produce neuroprotection by reversing cognitive deficits along with Aβ-induced neuroinflammation, oxidative responses, and neuronal death, delaying AD progression. Their exact signaling mechanisms need to be elucidated for understanding the brain intrinsic repair mechanism. The aim of this review was to shed light on physiology and pathophysiology of AD and to summarize the experimental data on neuroprotective roles of FAAH and MAGL inhibitors. In this review, we have also included CB1R and CB2R modulators with their diverse roles to modulate ECS mediated responses such as anti-nociceptive, anxiolytic, and anti-inflammatory actions in AD. Future research would provide the directions in understanding the molecular mechanisms and development of new therapeutic interventions for the treatment of AD.
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Affiliation(s)
- Hina Kanwal
- Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (M.S.); (M.C.); (R.V.); (A.D.R.); (G.S.); (T.C.)
| | - Moris Sangineto
- Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (M.S.); (M.C.); (R.V.); (A.D.R.); (G.S.); (T.C.)
| | - Martina Ciarnelli
- Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (M.S.); (M.C.); (R.V.); (A.D.R.); (G.S.); (T.C.)
| | - Pasqualina Castaldo
- Department of Biomedical Sciences and Public Health, School of Medicine, University “Politecnica delle Marche”, 60126 Ancona, Italy;
| | - Rosanna Villani
- Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (M.S.); (M.C.); (R.V.); (A.D.R.); (G.S.); (T.C.)
| | - Antonino Davide Romano
- Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (M.S.); (M.C.); (R.V.); (A.D.R.); (G.S.); (T.C.)
| | - Gaetano Serviddio
- Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (M.S.); (M.C.); (R.V.); (A.D.R.); (G.S.); (T.C.)
| | - Tommaso Cassano
- Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (M.S.); (M.C.); (R.V.); (A.D.R.); (G.S.); (T.C.)
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11
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Wang Y, Deng X, Zhang R, Lyu H, Xiao S, Guo D, Ali DW, Michalak M, Zhou C, Chen XZ, Tang J. The TRPV6 Calcium Channel and Its Relationship with Cancer. BIOLOGY 2024; 13:168. [PMID: 38534438 DOI: 0.3390/biology13030168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 02/22/2024] [Accepted: 02/28/2024] [Indexed: 10/14/2024]
Abstract
Transient receptor potential vanilloid-6 (TRPV6) is a cation channel belonging to the TRP superfamily, specifically the vanilloid subfamily, and is the sixth member of this subfamily. Its presence in the body is primarily limited to the skin, ovaries, kidney, testes, and digestive tract epithelium. The body maintains calcium homeostasis using the TRPV6 channel, which has a greater calcium selectivity than the other TRP channels. Several pieces of evidence suggest that it is upregulated in the advanced stages of thyroid, ovarian, breast, colon, and prostate cancers. The function of TRPV6 in regulating calcium signaling in cancer will be covered in this review, along with its potential applications as a cancer treatment target.
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Affiliation(s)
- Yifang Wang
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China
- Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan 430068, China
| | - Xiaoling Deng
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China
- Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan 430068, China
| | - Rui Zhang
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China
| | - Hao Lyu
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China
| | - Shuai Xiao
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China
| | - Dong Guo
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China
| | - Declan William Ali
- Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada
| | - Marek Michalak
- Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada
| | - Cefan Zhou
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China
| | - Xing-Zhen Chen
- Membrane Protein Disease Research Group, Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada
| | - Jingfeng Tang
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China
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12
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Wang Y, Deng X, Zhang R, Lyu H, Xiao S, Guo D, Ali DW, Michalak M, Zhou C, Chen XZ, Tang J. The TRPV6 Calcium Channel and Its Relationship with Cancer. BIOLOGY 2024; 13:168. [PMID: 38534438 PMCID: PMC10968549 DOI: 10.3390/biology13030168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 02/22/2024] [Accepted: 02/28/2024] [Indexed: 03/28/2024]
Abstract
Transient receptor potential vanilloid-6 (TRPV6) is a cation channel belonging to the TRP superfamily, specifically the vanilloid subfamily, and is the sixth member of this subfamily. Its presence in the body is primarily limited to the skin, ovaries, kidney, testes, and digestive tract epithelium. The body maintains calcium homeostasis using the TRPV6 channel, which has a greater calcium selectivity than the other TRP channels. Several pieces of evidence suggest that it is upregulated in the advanced stages of thyroid, ovarian, breast, colon, and prostate cancers. The function of TRPV6 in regulating calcium signaling in cancer will be covered in this review, along with its potential applications as a cancer treatment target.
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Affiliation(s)
- Yifang Wang
- National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China; (Y.W.); (X.D.); (R.Z.); (H.L.); (S.X.); (D.G.); (C.Z.)
- Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan 430068, China
| | - Xiaoling Deng
- National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China; (Y.W.); (X.D.); (R.Z.); (H.L.); (S.X.); (D.G.); (C.Z.)
- Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan 430068, China
| | - Rui Zhang
- National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China; (Y.W.); (X.D.); (R.Z.); (H.L.); (S.X.); (D.G.); (C.Z.)
| | - Hao Lyu
- National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China; (Y.W.); (X.D.); (R.Z.); (H.L.); (S.X.); (D.G.); (C.Z.)
| | - Shuai Xiao
- National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China; (Y.W.); (X.D.); (R.Z.); (H.L.); (S.X.); (D.G.); (C.Z.)
| | - Dong Guo
- National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China; (Y.W.); (X.D.); (R.Z.); (H.L.); (S.X.); (D.G.); (C.Z.)
| | - Declan William Ali
- Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada;
| | - Marek Michalak
- Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada;
| | - Cefan Zhou
- National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China; (Y.W.); (X.D.); (R.Z.); (H.L.); (S.X.); (D.G.); (C.Z.)
| | - Xing-Zhen Chen
- Membrane Protein Disease Research Group, Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada
| | - Jingfeng Tang
- National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China; (Y.W.); (X.D.); (R.Z.); (H.L.); (S.X.); (D.G.); (C.Z.)
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Pinheiro EF, Cardoso PB, Luz WL, Assad N, Santos-Silva M, Leão LKR, de Moraes SAS, Passos ADC, de Jesus Oliveira Batista E, Oliveira KRHM, Gouveia A, Herculano AM. Putative Activation of Cannabinoid Receptor Type 1 Prevents Brain Oxidative Stress and Inhibits Aggressive-Like Behavior in Zebrafish. Cannabis Cannabinoid Res 2024; 9:65-73. [PMID: 36576997 DOI: 10.1089/can.2022.0146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Background: Aggression is a set of complex behaviors commonly described in different neurological disorders, such as schizophrenia, autistim spectrum disorder, and anxiety. Previous studies have described that some changes in the redox status of the brain are closely associated with aggressive behavior in different species. In addition, the endocannabinoid system acts as a neuromodulator of the central nervous system, however, its participation in aggressive behavior needs to be elucidated. Danio rerio (zebrafish) is an important model in the study of aggression, in this context, the present study investigated whether the activation of type 1 cannabinoid receptors (CB1r) alters the cerebral redox state and aggressive behavior in zebrafish. Materials and Methods: We performed pharmacological manipulations with the CB1r agonist (ACEA) and antagonist (AM-251) to assess the role of this receptor in aggressive behavior. Individuals were isolated in pairs, without physical contact for 24 h, treated with the drugs of interest, and after 30 minutes of pharmacokinetics, the fights were filmed for 30 min, and the individuals were identified as dominant or subordinate. Results: A consistent decrease in the strike and bite aggressive behavior was observed in the group treated with the ACEA agonist compared with that in the control and AM-251 groups. When evaluating the cerebral redox state, we observed that treatment with the ACEA agonist reduced malondialdehyde (MDA) levels and increased the levels of sulfhydryl groups compared with those in the control group. These results indicate that the activation of CB1r by the ACEA agonist inhibited aggressiveness and attenuated the levels of oxidative stress in both subjects (dominant or subordinate) in the treated group. Conclusion: Thus, we suggest that zebrafish is an alternative model to study common aggressive behavior disorders among species and that CB1r represent a potential target for the development of treatments for aggressive disorders.
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Affiliation(s)
- Emerson Feio Pinheiro
- Laboratory of Experimental Neuropharmacology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
| | - Patrick Bruno Cardoso
- Laboratory of Experimental Neuropharmacology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
| | - Waldo Lucas Luz
- Laboratory of Experimental Neuropharmacology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
| | - Nadyme Assad
- Department of Psychobiology, Federal University of São Paulo, São Paulo, Brazil
| | - Mateus Santos-Silva
- Laboratory of Experimental Neuropharmacology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
| | - Luana Ketlen Reis Leão
- Laboratory of Experimental Neuropharmacology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
| | | | - Adelaide da Conceição Passos
- Laboratory of Experimental Neuropharmacology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
| | - Evander de Jesus Oliveira Batista
- Laboratory of Experimental Neuropharmacology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
- Laboratory of Protozoology, Tropical Medicine Center, Federal University of Pará, Belém, Brazil
| | | | - Amauri Gouveia
- Laboratory of Neuroscience and Behavior, Federal University of Pará, Belém, Brazil
| | - Anderson Manoel Herculano
- Laboratory of Experimental Neuropharmacology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
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Alzu'bi A, Almahasneh F, Khasawneh R, Abu-El-Rub E, Baker WB, Al-Zoubi RM. The synthetic cannabinoids menace: a review of health risks and toxicity. Eur J Med Res 2024; 29:49. [PMID: 38216984 PMCID: PMC10785485 DOI: 10.1186/s40001-023-01443-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 10/10/2023] [Indexed: 01/14/2024] Open
Abstract
Synthetic cannabinoids (SCs) are chemically classified as psychoactive substances that target the endocannabinoid system in many body organs. SCs can initiate pathophysiological changes in many tissues which can be severe enough to damage the normal functionality of our body systems. The majority of SCs-related side effects are mediated by activating Cannabinoid Receptor 1 (CB1R) and Cannabinoid Receptor 2 (CB2R). The activation of these receptors can enkindle many downstream signalling pathways, including oxidative stress, inflammation, and apoptosis that ultimately can produce deleterious changes in many organs. Besides activating the cannabinoid receptors, SCs can act on non-cannabinoid targets, such as the orphan G protein receptors GPR55 and GPR18, the Peroxisome Proliferator-activated Receptors (PPARs), and the Transient receptor potential vanilloid 1 (TRPV1), which are broadly expressed in the brain and the heart and their activation mediates many pharmacological effects of SCs. In this review, we shed light on the multisystem complications found in SCs abusers, particularly discussing their neurologic, cardiovascular, renal, and hepatic effects, as well as highlighting the mechanisms that intermediate SCs-related pharmacological and toxicological consequences to provide comprehensive understanding of their short and long-term systemic effects.
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Affiliation(s)
- Ayman Alzu'bi
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, 211-63, Jordan.
| | - Fatimah Almahasneh
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, 211-63, Jordan
| | - Ramada Khasawneh
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, 211-63, Jordan
| | - Ejlal Abu-El-Rub
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, 211-63, Jordan
| | - Worood Bani Baker
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, 211-63, Jordan
| | - Raed M Al-Zoubi
- Surgical Research Section, Department of Surgery, Hamad Medical Corporation & Men'S Health, Doha, Qatar.
- Department of Biomedical Sciences, QU-Health, College of Health Sciences, Qatar University, Doha, 2713, Qatar.
- Department of Chemistry, Jordan University of Science and Technology, P.O.Box 3030, Irbid, 22110, Jordan.
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15
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Guo Y, Wei R, Deng J, Guo W. Research progress in the management of vascular disease with cannabidiol: a review. J Cardiothorac Surg 2024; 19:6. [PMID: 38172934 PMCID: PMC10765825 DOI: 10.1186/s13019-023-02476-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 12/25/2023] [Indexed: 01/05/2024] Open
Abstract
The morbidity and mortality rates associated with vascular disease (VD) have been gradually increasing. Currently, the most common treatment for VD is surgery, with the progress in drug therapy remaining slow. Cannabidiol (CBD) is a natural extract of Cannabis sativa L. with sedative, analgesic, and nonaddictive properties. CBD binds to 56 cardiovascular-related receptors and exerts extensive regulatory effects on the cardiovascular system, making it a potential pharmacological agent for the management of VD. However, most CBD studies have focused on neurological and cardiac diseases, and research on the management of VD with CBD is still rare. In this review, we summarize the currently available data on CBD in the management of VD, addressing four aspects: the major molecular targets of CBD in VD management, pharmacokinetic properties, therapeutic effects of CBD on common VDs, and side effects. The findings indicate that CBD has anti-anxiety, anti-oxidation, and anti-inflammatory properties and can inhibit abnormal proliferation and apoptosis of vascular smooth muscle and endothelial cells; these effects suggest CBD as a therapeutic agent for atherosclerosis, stress-induced hypertension, diabetes-related vasculopathy, ischemia-reperfusion injury, and vascular damage caused by smoking and alcohol abuse. This study provides a theoretical basis for further research on CBD in the management of VD.
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Affiliation(s)
- Yilong Guo
- Medical School of Chinese PLA, Beijing, 100037, China
- Department of Vascular and Endovascular Surgery, The First Medical Centre of PLA General Hospital, 28#, Fuxing Road, Beijing, 100037, China
| | - Ren Wei
- Department of Vascular and Endovascular Surgery, The First Medical Centre of PLA General Hospital, 28#, Fuxing Road, Beijing, 100037, China
| | - Jianqing Deng
- Senior Department of Cardiology, The Six Medical Centre of PLA General Hospital, Beijing, 100037, China
| | - Wei Guo
- Medical School of Chinese PLA, Beijing, 100037, China.
- Department of Vascular and Endovascular Surgery, The First Medical Centre of PLA General Hospital, 28#, Fuxing Road, Beijing, 100037, China.
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Liu ST, Zha KJ, Li PJ, Gao JB, Zhang YG. Protective effect of naringin against radiation-induced heart disease in rats via Sirt1/NF-κB signaling pathway and endoplasmic reticulum stress. Chem Biol Drug Des 2024; 103:e14453. [PMID: 38230793 DOI: 10.1111/cbdd.14453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 12/01/2023] [Accepted: 12/06/2023] [Indexed: 01/18/2024]
Abstract
This study was designed to explore the protective effect and mechanism of naringin (NG) on radiation-induced heart disease (RIHD) in rats. Rats were divided into four x-ray (XR) irradiation groups with different absorbed doses (0/10/15/20 Gy), or into three groups (control, XR, and XR + NG groups). Subsequently, the ultrasonic diagnostic apparatus was adopted to assess and compare the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular internal diameter at end diastole (LVIDd), and left ventricular internal diameter at end systole (LVIDs) in rats. Hematoxylin-eosin (H&E) staining and Masson staining were applied to detect the pathological damage and fibrosis of heart tissue. Western blot was used to measure the expression levels of myocardial fibrosis-related proteins, endoplasmic reticulum stress-related proteins, and Sirt1 (silent information regulator 1)/NF-κB (nuclear factor kappa-B) signaling pathway-related proteins in cardiac tissues. Additionally, enzyme-linked immunosorbent assay was utilized to detect the activities of pro-inflammatory cytokines, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) in cardiac tissue. The results showed that NG treatment significantly attenuated the 20 Gy XR-induced decline of LVEF and LVFS and the elevation of LVIDs. Cardiac tissue damage and fibrosis caused by 20 Gy XR were significant improved after NG treatment. Meanwhile, in rats irradiated by XR, marked downregulation was identified in the expressions of fibrosis-related proteins (Col I, collagen type I; α-SMA, α-smooth muscle actin; and TGF-β1, transforming growth factor-beta 1) and endoplasmic reticulum stress-related proteins (GRP78, glucose regulatory protein 78; CHOP, C/EBP homologous protein; ATF6, activating transcription factor 6; and caspase 12) after NG treatment. Moreover, NG treatment also inhibited the production of pro-inflammatory cytokines [interleukin-6, interleukin-1β, and monocyte chemoattractant protein-1 (MCP-1)], reduced the expression of MDA, and promoted the activities of SOD and CAT. Also, NG treatment promoted Sirt1 expression and inhibited p65 phosphorylation. Collectively, XR irradiation induced cardiac injury in rats in a dose-dependent manner. NG could improve the cardiac injury induced by XR irradiation by inhibiting endoplasmic reticulum stress and activating Sirt1/NF-κB signaling pathway.
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Affiliation(s)
- Shu-Ting Liu
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Kai-Ji Zha
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Pei-Jie Li
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Jian-Bo Gao
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yong-Gao Zhang
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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Ulug P, Nayki U, Mammadov R, Bulut S, Tastan TB, Coban TA, Suleyman H. Protective Effect of Ramipril Against Oxidant and Proinflammatory Cytokine Damage Induced by Ischemia-Reperfusion in Ovarian Tissue in Rats. Transplant Proc 2024; 56:215-222. [PMID: 38218697 DOI: 10.1016/j.transproceed.2023.11.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 11/26/2023] [Indexed: 01/15/2024]
Abstract
BACKGROUND It is known that the increase in oxidants and proinflammatory cytokines, as well as the decrease in antioxidants, play a role in ovarian ischemia-reperfusion (I/R) injury. The antioxidant and anti-inflammatory properties of ramipril have been studied in various diseases. This study aims to investigate the effect of ramipril on I/R-induced ovarian damage in rats. METHODS Rats were divided into healthy (HG), sham (SG), ovary I/R (OIR), and ramipril + ovary I/R (ROIR) groups (n = 6/each group). One hour before the surgical procedures, ROIR was given 2 mg/kg ramipril. The lower abdomen of the SG, OIR, and ROIR was surgically opened. Right ovarian tissues of OIR and ROIR were subjected to 2 hours of ischemia and 6 hours of reperfusion. Then, all animals were euthanized, and their right ovaries were removed. Ovarian tissues were examined for oxidants (malondialdehyde), antioxidants (total glutathione, superoxide dismutase, and catalase), and proinflammatory cytokines (nuclear factor kappa-B, tumor necrosis factor-alpha, interleukin 1 beta, and interleukin-6) analysis was performed. Tissues were examined histopathologically. RESULTS The ovarian tissue of the OIR, which underwent the I/R procedure, exhibited a significant increase in oxidant and proinflammatory cytokine levels, along with a decrease in antioxidant levels (P < .001). Ramipril suppressed the I/R-induced increase in oxidants and pro-inflammatory cytokines and the decrease in antioxidants (P < .001). Ramipril also attenuated I/R-induced histopathological damage in ovarian tissue (P < .05). CONCLUSION Ramipril treatment may be a treatment strategy to protect ovarian tissue against oxidative and inflammatory damage of I/R.
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Affiliation(s)
- Pasa Ulug
- Department of Gynecology and Obstetrics, School of Medicine, Erzincan Binali Yıldırım University, Erzincan, Turkey.
| | - Umit Nayki
- Department of Gynecology and Obstetrics, School of Medicine, Erzincan Binali Yıldırım University, Erzincan, Turkey
| | - Renad Mammadov
- Department of Pharmacology, School of Medicine, Erzincan Binali Yıldırım University, Erzincan, Turkey
| | - Seval Bulut
- Department of Pharmacology, School of Medicine, Erzincan Binali Yıldırım University, Erzincan, Turkey
| | - Tugba Bal Tastan
- Department of Histology and Embryology, School of Medicine, Erzincan Binali Yıldırım University, Erzincan, Turkey
| | - Taha Abdulkadir Coban
- Department of Medical Biochemistry, School of Medicine, Erzincan Binali Yıldırım University, Erzincan, Turkey
| | - Halis Suleyman
- Department of Pharmacology, School of Medicine, Erzincan Binali Yıldırım University, Erzincan, Turkey
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18
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Wang Y, Ji X, Wang X, Sun M, Li C, Wu D. The injectable hydrogel loading cannabidiol to regulate macrophage polarization in vitro for the treatment of chronic enteritis. J Appl Biomater Funct Mater 2024; 22:22808000241289022. [PMID: 39385453 DOI: 10.1177/22808000241289022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/12/2024] Open
Abstract
OBJECTIVE Chronic bowel disease has the characteristics of high recurrence rate, prolonged and non-healing, and the incidence has increased year by year in recent years. Cannabidiol (CBD) has significant anti-inflammatory and antioxidant activities, but it is limited by its characteristics of fat solubility and low bioavailability. This study aims to treat chronic inflammatory bowel disease by preparing a CBD-loaded hydrogel system (GelMA + CBD) that can deliver CBD in situ and improve its bioavailability through slow release. METHOD The study designed and constructed GelMA + CBD, and its surface morphology was observed by scanning electron microscopy, and its pore size, swelling rate and release rate were evaluated to evaluate its bioactivity and biosafety. The expression of various inflammatory factors was detected by ELISA, and the expression of protein and reactive oxygen species were observed by laser confocal microscopy to evaluate their anti-inflammatory and antioxidant properties. RESULTS Our study found that GelMA + CBD with biosafety, could make CBD be slowly released, and effectively inhibit the M1-type polarization of macrophages in vitro, and promote the M2-type polarization. In addition, GelMA + CBD can also reduce the expression of pro-inflammatory factors (such as iNOS) in macrophages, and increase the expression of anti-inflammatory factors (such as Arg-1), clear intracellular reactive oxygen species (ROS), and relieve oxidative stress. CONCLUSION The vitro experiments have confirmed that the CBD-loaded hydrogel system has good biosafety, and can alleviate inflammation by regulating the polarization direction of macrophages, and then inhibiting the secretion of pro-inflammatory factors, laying a strong foundation for the treatment of chronic enteritis.
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Affiliation(s)
- Ye Wang
- Key Laboratory of Microecology-Immune Regulatory Network and Related Diseases School of Basic Medicine, Jiamusi University, Jiamusi, Heilongjiang Province, China
- Tianjin First Central Hospital, Tianjin, China
| | - Xingming Ji
- Tianjin First Central Hospital, Tianjin, China
- School of Medicine, Nankai University, Tianjin, China
| | - Xinyi Wang
- Tianjin First Central Hospital, Tianjin, China
| | - Mengyu Sun
- Tianjin First Central Hospital, Tianjin, China
| | - Cheng Li
- Tianjin First Central Hospital, Tianjin, China
- School of Medicine, Nankai University, Tianjin, China
| | - Dongmei Wu
- School of Basic Medicine, Jiamusi University, Jiamusi, Heilongjiang, China
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19
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Šahinović I, Mandić S, Mihić D, Duvnjak M, Loinjak D, Sabadi D, Majić Z, Perić L, Šerić V. Endocannabinoids, Anandamide and 2-Arachidonoylglycerol, as Prognostic Markers of Sepsis Outcome and Complications. Cannabis Cannabinoid Res 2023; 8:802-811. [PMID: 35649233 PMCID: PMC10589499 DOI: 10.1089/can.2022.0046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Background: One of the major challenges in improving sepsis care is early prediction of sepsis complications. The endocannabinoid system has been intensely studied in recent years; however, little is known about its role in sepsis in humans. This study aimed to assess the prognostic role of endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), as early predictors of mortality, invasive mechanical ventilation (IMV) requirement, and length of stay (LOS) in patients with sepsis. Materials and Methods: In total, 106 patients with confirmed sepsis were enrolled in this study. The patients were divided into groups according to mortality outcome (survival, N=53; nonsurvival, N=53), IMV requirement (IMV group, N=26; non-IMV group, N=80), and LOS (LOS <10 days, N=59; LOS ≥10 days, N=47). Patients' clinical status was assessed along with laboratory biomarkers as well as AEA and 2-AG concentration measurements early on admission to emergency units. AEA and 2-AG levels were measured by enzyme-linked immunosorbent assay (ELISA) using an ELISA processor, EtiMax 3000 (DiaSorin, Saluggia, Italy). The predictive value of AEA and 2-AG for the studied sepsis outcomes and complications was analyzed using univariate and multivariate analyses and receiver operating characteristic (ROC) curve analysis. Results: Two endocannabinoids showed no significant difference between survivors and nonsurvivors, although an AEA concentration <7.16 μg/L predicted mortality outcome with a sensitivity of 57% (95% confidence interval [CI] 42-71) and specificity of 80% (95% CI 66-91). AEA concentrations ≤17.84 μg/L predicted LOS ≥10 days with sensitivity of 98% (95% CI 89-100) and specificity of 34% (95% CI 22-47). When analyzing IMV requirement, levels of AEA and 2-AG were significantly lower within the IMV group compared with the non-IMV group (5.94 μg/L [2.04-9.44] and 6.70 μg/L [3.50-27.04], p=0.043, and 5.68 μg/L [2.30-8.60] and 9.58 μg/L [4.83-40.05], p=0.002, respectively). The 2-AG showed the best performance for IMV requirement prediction, with both sensitivity and specificity of 69% (p<0.001). Endocannabinoid AEA was an independent risk factor of LOS ≥10 days (odds ratio [OR] 23.59; 95% CI 3.03-183.83; p=0.003) and IMV requirement in sepsis (OR 0.79; 95% CI, 0.67-0.93; p=0.004). Conclusion: Low AEA concentration is a prognostic factor of hospital LOS longer than 10 days. Lower AEA and 2-AG concentrations obtained at the time of admission to the hospital are predictors of IMV requirement.
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Affiliation(s)
- Ines Šahinović
- Department of Clinical Laboratory Diagnostics, University Hospital Osijek, Osijek, Croatia
- J.J. Strossmayer University of Osijek, Faculty of Medicine Osijek, Osijek, Croatia
| | - Sanja Mandić
- Department of Clinical Laboratory Diagnostics, University Hospital Osijek, Osijek, Croatia
- J.J. Strossmayer University of Osijek, Faculty of Medicine Osijek, Osijek, Croatia
| | - Damir Mihić
- J.J. Strossmayer University of Osijek, Faculty of Medicine Osijek, Osijek, Croatia
- Department of Pulmonology and Intensive Care, Clinic of Internal Medicine, University Hospital Osijek, Osijek, Croatia
| | - Mario Duvnjak
- J.J. Strossmayer University of Osijek, Faculty of Medicine Osijek, Osijek, Croatia
- Clinic of Infective Diseases, University Hospital Osijek, Osijek, Croatia
| | - Domagoj Loinjak
- J.J. Strossmayer University of Osijek, Faculty of Medicine Osijek, Osijek, Croatia
- Department of Pulmonology and Intensive Care, Clinic of Internal Medicine, University Hospital Osijek, Osijek, Croatia
| | - Dario Sabadi
- J.J. Strossmayer University of Osijek, Faculty of Medicine Osijek, Osijek, Croatia
- Clinic of Infective Diseases, University Hospital Osijek, Osijek, Croatia
| | - Zlatko Majić
- Department of Pulmonology and Intensive Care, Clinic of Internal Medicine, University Hospital Osijek, Osijek, Croatia
| | - Ljiljana Perić
- J.J. Strossmayer University of Osijek, Faculty of Medicine Osijek, Osijek, Croatia
- Clinic of Infective Diseases, University Hospital Osijek, Osijek, Croatia
| | - Vatroslav Šerić
- Department of Clinical Laboratory Diagnostics, University Hospital Osijek, Osijek, Croatia
- J.J. Strossmayer University of Osijek, Faculty of Medicine Osijek, Osijek, Croatia
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20
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Biernacki M, Conde T, Stasiewicz A, Surażyński A, Domingues MR, Domingues P, Skrzydlewska E. Restorative Effect of Microalgae Nannochloropsis oceanica Lipid Extract on Phospholipid Metabolism in Keratinocytes Exposed to UVB Radiation. Int J Mol Sci 2023; 24:14323. [PMID: 37762626 PMCID: PMC10532178 DOI: 10.3390/ijms241814323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 09/12/2023] [Accepted: 09/18/2023] [Indexed: 09/29/2023] Open
Abstract
Ultraviolet B (UVB) radiation induces oxidative stress in skin cells, generating reactive oxygen species (ROS) and perturbing enzyme-mediated metabolism. This disruption is evidenced with elevated concentrations of metabolites that play important roles in the modulation of redox homeostasis and inflammatory responses. Thus, this research sought to determine the impacts of the lipid extract derived from the Nannochloropsis oceanica microalgae on phospholipid metabolic processes in keratinocytes subjected to UVB exposure. UVB-irradiated keratinocytes were treated with the microalgae extract. Subsequently, analyses were performed on cell lysates to ascertain the levels of phospholipid/free fatty acids (GC-FID), lipid peroxidation byproducts (GC-MS), and endocannabinoids/eicosanoids (LC-MS), as well as to measure the enzymatic activities linked with phospholipid metabolism, receptor expression, and total antioxidant status (spectrophotometric methods). The extract from N. oceanica microalgae, by diminishing the activities of enzymes involved in the synthesis of endocannabinoids and eicosanoids (PLA2/COX1/2/LOX), augmented the concentrations of anti-inflammatory and antioxidant polyunsaturated fatty acids (PUFAs), namely DHA and EPA. These concentrations are typically diminished due to UVB irradiation. As a consequence, there was a marked reduction in the levels of pro-inflammatory arachidonic acid (AA) and associated pro-inflammatory eicosanoids and endocannabinoids, as well as the expression of CB1/TRPV1 receptors. The microalgal extract also mitigated the increase in lipid peroxidation byproducts, specifically MDA in non-irradiated samples and 10-F4t-NeuroP in both control and post-UVB exposure. These findings indicate that the lipid extract derived from N. oceanica, by mitigating the deleterious impacts of UVB radiation on keratinocyte phospholipids, assumed a pivotal role in reinstating intracellular metabolic equilibrium.
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Affiliation(s)
- Michał Biernacki
- Department of Analytical Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-069 Bialystok, Poland; (M.B.); (A.S.)
| | - Tiago Conde
- Mass Spectrometry Centre, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Santiago University Campus, 3810-193 Aveiro, Portugal; (T.C.); (M.R.D.); (P.D.)
- CESAM—Centre for Environmental and Marine Studies, Department of Chemistry, University of Aveiro, Santiago University Campus, 3810-193 Aveiro, Portugal
| | - Anna Stasiewicz
- Department of Analytical Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-069 Bialystok, Poland; (M.B.); (A.S.)
| | - Arkadiusz Surażyński
- Department of Medicinal Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-069 Bialystok, Poland;
| | - Maria Rosário Domingues
- Mass Spectrometry Centre, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Santiago University Campus, 3810-193 Aveiro, Portugal; (T.C.); (M.R.D.); (P.D.)
- CESAM—Centre for Environmental and Marine Studies, Department of Chemistry, University of Aveiro, Santiago University Campus, 3810-193 Aveiro, Portugal
| | - Pedro Domingues
- Mass Spectrometry Centre, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Santiago University Campus, 3810-193 Aveiro, Portugal; (T.C.); (M.R.D.); (P.D.)
| | - Elżbieta Skrzydlewska
- Department of Analytical Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-069 Bialystok, Poland; (M.B.); (A.S.)
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21
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Shen CL, Newman JW, Elmassry MM, Borkowski K, Chyu MC, Kahathuduwa C, Neugebauer V, Watkins BA. Tai Chi exercise reduces circulating levels of inflammatory oxylipins in postmenopausal women with knee osteoarthritis: results from a pilot study. Front Med (Lausanne) 2023; 10:1210170. [PMID: 37654656 PMCID: PMC10466388 DOI: 10.3389/fmed.2023.1210170] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 07/25/2023] [Indexed: 09/02/2023] Open
Abstract
Background Tai Chi (TC) controls pain through mind-body exercise and appears to alter inflammatory mediators. TC actions on lipid biomarkers associated with inflammation and brain neural networks in women with knee osteoarthritic pain were investigated. Methods A single-center, pre- and post-TC group (baseline and 8 wk) exercise pilot study in postmenopausal women with knee osteoarthritic pain was performed. 12 eligible women participated in TC group exercise. The primary outcome was liquid chromatography tandem mass spectrometry determination of circulating endocannabinoids (eCB) and oxylipins (OxL). Secondary outcomes were correlations between eCB and OxL levels and clinical pain/limitation assessments, and brain resting-state function magnetic resonance imaging (rs-fMRI). Results Differences in circulating quantitative levels (nM) of pro-inflammatory OxL after TC were found in women. TC exercise resulted in lower OxL PGE1 and PGE2 and higher 12-HETE, LTB4, and 12-HEPE compared to baseline. Pain assessment and eCB and OxL levels suggest crucial relationships between TC exercise, inflammatory markers, and pain. Higher plasma levels of eCB AEA, and 1, 2-AG were found in subjects with increased pain. Several eCB and OxL levels were positively correlated with left and right brain amygdala-medial prefrontal cortex functional connectivity. Conclusion TC exercise lowers pro-inflammatory OxL in women with knee osteoarthritic pain. Correlations between subject pain, functional limitations, and brain connectivity with levels of OxL and eCB showed significance. Findings indicate potential mechanisms for OxL and eCB and their biosynthetic endogenous PUFA precursors that alter brain connectivity, neuroinflammation, and pain. Clinical Trial Registration ClinicalTrials.gov, identifier: NCT04046003.
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Affiliation(s)
- Chwan-Li Shen
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX, United States
- Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX, United States
- Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX, United States
| | - John W. Newman
- United States Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, Davis, CA, United States
- Department of Nutrition, University of California, Davis, Davis, CA, United States
- West Coast Metabolomics Center, Genome Center, University of California, Davis, Davis, CA, United States
| | - Moamen M. Elmassry
- Department of Molecular Biology, Princeton University, Princeton, NJ, United States
| | - Kamil Borkowski
- West Coast Metabolomics Center, Genome Center, University of California, Davis, Davis, CA, United States
| | - Ming-Chien Chyu
- Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX, United States
- Department of Medical Engineering, Texas Tech University, Lubbock, TX, United States
| | - Chanaka Kahathuduwa
- Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX, United States
- Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX, United States
- Department of Neurology, Texas Tech University Health Sciences Center, Lubbock, TX, United States
- Department of Psychiatry, Texas Tech University Health Sciences Center, Lubbock, TX, United States
| | - Volker Neugebauer
- Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX, United States
- Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX, United States
- Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, United States
- Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, United States
| | - Bruce A. Watkins
- Department of Nutrition, University of California, Davis, Davis, CA, United States
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22
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Abdallah DM, Kamal MM, Aly NES, El-Abhar HS. Anandamide modulates WNT-5A/BCL-2, IP3/NFATc1, and HMGB1/NF-κB trajectories to protect against mercuric chloride-induced acute kidney injury. Sci Rep 2023; 13:11899. [PMID: 37488162 PMCID: PMC10366223 DOI: 10.1038/s41598-023-38659-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 07/12/2023] [Indexed: 07/26/2023] Open
Abstract
Endocannabinoid anandamide (AEA) has a physiological role in regulating renal blood flow, whereas its analogs ameliorated renal ischemia/reperfusion injury. Nonetheless, the role of AEA against mercuric chloride (HgCl2)-induced renal toxicity has not been unraveled. Rats were allocated into control, HgCl2, and HgCl2/AEA treated groups. The administration of AEA quelled the HgCl2-mediated increase in inositol trisphosphate (IP3) and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). The endocannabinoid also signified its anti-inflammatory potential by turning off the inflammatory cascade evidenced by the suppression of high mobility group box protein-1 (HMGB1), receptor of glycated end products (RAGE), nuclear factor-κB p65 (NF-κB), and unexpectedly PPAR-γ. Additionally, the aptitude of AEA to inhibit malondialdehyde and boost glutathione points to its antioxidant capacity. Moreover, AEA by enhancing the depleted renal WNT-5A and reducing cystatin-C and KIM-1 (two kidney function parameters) partly verified its anti-apoptotic capacity, confirmed by inhibiting caspase-3 and increasing B-cell lymphoma-2 (BCL-2). The beneficial effect of AEA was mirrored by the improved architecture and kidney function evidenced by the reduction in cystatin-C, KIM-1, creatinine, BUN, and caspase1-induced activated IL-18. In conclusion, our results verify the reno-protective potential of AEA against HgCl2-induced kidney injury by its anti-inflammatory, antioxidant, and anti-apoptotic capacities by modulating WNT-5A/BCL-2, IP3/NFATC1, HMGB-1/RAGE/NF-κB, caspase-1/IL-18, and caspase-3/BCL-2 cues.
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Affiliation(s)
- Dalaal M Abdallah
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
| | - Mahmoud M Kamal
- Research Institute of Medical Entomology, General Organization for Teaching Hospitals and Institutes, Cairo, Egypt
| | - Nour Eldin S Aly
- Research Institute of Medical Entomology, General Organization for Teaching Hospitals and Institutes, Cairo, Egypt
| | - Hanan S El-Abhar
- Department of Pharmacology, Toxicology, and Biochemistry, Faculty of Pharmacy, Future University in Egypt (FUE), Cairo, 11835, Egypt
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23
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Jîtcă G, Ősz BE, Vari CE, Rusz CM, Tero-Vescan A, Pușcaș A. Cannabidiol: Bridge between Antioxidant Effect, Cellular Protection, and Cognitive and Physical Performance. Antioxidants (Basel) 2023; 12:antiox12020485. [PMID: 36830042 PMCID: PMC9952814 DOI: 10.3390/antiox12020485] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/08/2023] [Accepted: 02/13/2023] [Indexed: 02/17/2023] Open
Abstract
The literature provides scientific evidence for the beneficial effects of cannabidiol (CBD), and these effects extend beyond epilepsy treatment (e.g., Lennox-Gastaut and Dravet syndromes), notably the influence on oxidative status, neurodegeneration, cellular protection, cognitive function, and physical performance. However, products containing CBD are not allowed to be marketed everywhere in the world, which may ultimately have a negative effect on health as a result of the uncontrolled CBD market. After the isolation of CBD follows the discovery of CB1 and CB2 receptors and the main enzymatic components (diacylglycerol lipase (DAG lipase), monoacyl glycerol lipase (MAGL), fatty acid amino hydrolase (FAAH)). At the same time, the antioxidant potential of CBD is due not only to the molecular structure but also to the fact that this compound increases the expression of the main endogenous antioxidant systems, superoxide dismutase (SOD), and glutathione peroxidase (GPx), through the nuclear complex erythroid 2-related factor (Nrf2)/Keep1. Regarding the role in the control of inflammation, this function is exercised by inhibiting (nuclear factor kappa B) NF-κB, and also the genes that encode the expression of molecules with a pro-inflammatory role (cytokines and metalloproteinases). The other effects of CBD on cognitive function and physical performance should not be excluded. In conclusion, the CBD market needs to be regulated more thoroughly, given the previously listed properties, with the mention that the safety profile is a very good one.
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Affiliation(s)
- George Jîtcă
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540139 Târgu Mureș, Romania
| | - Bianca E. Ősz
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540139 Târgu Mureș, Romania
- Correspondence:
| | - Camil E. Vari
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540139 Târgu Mureș, Romania
| | - Carmen-Maria Rusz
- Doctoral School of Medicine and Pharmacy, I.O.S.U.D, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540139 Târgu Mureș, Romania
| | - Amelia Tero-Vescan
- Department of Biochemistry, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540139 Târgu Mureș, Romania
| | - Amalia Pușcaș
- Department of Biochemistry, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540139 Târgu Mureș, Romania
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24
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Khavandi M, Rao PPN, Beazely MA. Differential Effects of Endocannabinoids on Amyloid-Beta Aggregation and Toxicity. Int J Mol Sci 2023; 24:911. [PMID: 36674424 PMCID: PMC9861930 DOI: 10.3390/ijms24020911] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 12/13/2022] [Accepted: 12/28/2022] [Indexed: 01/06/2023] Open
Abstract
The regulation and metabolism of the endocannabinoid system has received extensive attention for their potential neuroprotective effect in neurodegenerative diseases such as Alzheimer's disease (AD), which is characterized by amyloid β (Aβ) -induced cell toxicity, inflammation, and oxidative stress. Using in vitro techniques and two cell lines, the mouse hippocampus-derived HT22 cells and Chinese hamster ovary (CHO) cells expressing human cannabinoid receptor type 1 (CB1), we investigated the ability of endocannabinoids to inhibit Aβ aggregation and protect cells against Aβ toxicity. The present study provides evidence that endocannabinoids N-arachidonoyl ethanol amide (AEA), noladin and O-arachidonoyl ethanolamine (OAE) inhibit Aβ42 aggregation. They were able to provide protection against Aβ42 induced cytotoxicity via receptor-mediated and non-receptor-mediated mechanisms in CB1-CHO and HT22 cells, respectively. The aggregation kinetic experiments demonstrate the anti-Aβ aggregation activity of some endocannabinoids (AEA, noladin). These data demonstrate the potential role and application of endocannabinoids in AD pathology and treatment.
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Affiliation(s)
| | | | - Michael A. Beazely
- School of Pharmacy, Health Sciences Campus, University of Waterloo, Waterloo, ON N2L 3G1, Canada
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25
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Kamaruzzaman MA, Romli MH, Abas R, Vidyadaran S, Hidayat Baharuldin MT, Nasaruddin ML, Thirupathirao V, Sura S, Warsito K, Mohd Nor NH, Azwaruddin MA, Alshawsh MA, Mohd Moklas MA. Regulatory role of the endocannabinoid system on glial cells toward cognitive function in Alzheimer's disease: A systematic review and meta-analysis of animal studies. Front Pharmacol 2023; 14:1053680. [PMID: 36959856 PMCID: PMC10028478 DOI: 10.3389/fphar.2023.1053680] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 02/08/2023] [Indexed: 03/06/2023] Open
Abstract
Objective: Over the last decade, researchers have sought to develop novel medications against dementia. One potential agent under investigation is cannabinoids. This review systematically appraised and meta-analyzed published pre-clinical research on the mechanism of endocannabinoid system modulation in glial cells and their effects on cognitive function in animal models of Alzheimer's disease (AD). Methods: A systematic review complying with PRISMA guidelines was conducted. Six databases were searched: EBSCOHost, Scopus, PubMed, CINAHL, Cochrane, and Web of Science, using the keywords AD, cannabinoid, glial cells, and cognition. The methodological quality of each selected pre-clinical study was evaluated using the SYRCLE risk of bias tool. A random-effects model was applied to analyze the data and calculate the effect size, while I2 and p-values were used to assess heterogeneity. Results: The analysis included 26 original articles describing (1050 rodents) with AD-like symptoms. Rodents treated with cannabinoid agonists showed significant reductions in escape latency (standard mean difference [SMD] = -1.26; 95% confidence interval [CI]: -1.77 to -0.76, p < 0.00001) and ability to discriminate novel objects (SMD = 1.40; 95% CI: 1.04 to 1.76, p < 0.00001) compared to the control group. Furthermore, a significant decrease in Aβ plaques (SMD = -0.91; 95% CI: -1.55 to -0.27, p = 0.006) was observed in the endocannabinoid-treated group compared to the control group. Trends were observed toward neuroprotection, as represented by decreased levels of glial cell markers including glial fibrillary acid protein (SMD = -1.47; 95% CI: -2.56 to -0.38, p = 0.008) and Iba1 (SMD = -1.67; 95% CI: -2.56 to -0.79, p = 0.0002). Studies on the wild-type mice demonstrated significantly decreased levels of pro-inflammatory markers TNF-α, IL-1, and IL-6 (SMD = -2.28; 95% CI: -3.15 to -1.41, p = 0.00001). Despite the non-significant decrease in pro-inflammatory marker levels in transgenic mice (SMD = -0.47; 95% CI: -1.03 to 0.08, p = 0.09), the result favored the endocannabinoid-treated group over the control group. Conclusion: The revised data suggested that endocannabinoid stimulation promotes cognitive function via modulation of glial cells by decreasing pro-inflammatory markers in AD-like rodent models. Thus, cannabinoid agents may be required to modulate the downstream chain of effect to enhance cognitive stability against concurrent neuroinflammation in AD. Population-based studies and well-designed clinical trials are required to characterize the acceptability and real-world effectiveness of cannabinoid agents. Systematic Review Registration: [https://inplasy.com/inplasy-2022-8-0094/], identifier [Inplasy Protocol 3770].
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Affiliation(s)
- Mohd Amir Kamaruzzaman
- Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
- Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Kuala Lumpur, Malaysia
| | - Muhammad Hibatullah Romli
- Department of Nursing and Rehabilitation, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Kuala Lumpur, Malaysia
| | - Razif Abas
- Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Kuala Lumpur, Malaysia
| | - Sharmili Vidyadaran
- Department of Pathology, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Kuala Lumpur, Malaysia
| | | | | | | | - Sreenivasulu Sura
- Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Kuala Lumpur, Malaysia
- Department of Preclinical Sciences, Faculty of Medicine and Health Sciences, University Tunku Abdul Rahman, Kampar, Malaysia
| | - Kabul Warsito
- Department of Agrotechnology, Faculty of Science and Technology, University of Pembangunan Panca Budi, Medan, Indonesia
| | - Nurul Huda Mohd Nor
- Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Kuala Lumpur, Malaysia
| | - Muhammad Amsyar Azwaruddin
- Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Kuala Lumpur, Malaysia
| | - Mohammed Abdullah Alshawsh
- Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
- Department of Paediatrics, School of Clinical Sciences, Faculty of Medicine, Nursing and Health Science, Monash University, Clayton, VIC, Australia
- *Correspondence: Mohamad Aris Mohd Moklas, ; Mohammed Abdullah Alshawsh,
| | - Mohamad Aris Mohd Moklas
- Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Kuala Lumpur, Malaysia
- *Correspondence: Mohamad Aris Mohd Moklas, ; Mohammed Abdullah Alshawsh,
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Guerra J, Naidoo V, Cacabelos R. Potential effects of cannabinoids on audiovestibular function: A narrative review. Front Pharmacol 2022; 13:1010296. [PMID: 36605398 PMCID: PMC9807921 DOI: 10.3389/fphar.2022.1010296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 11/23/2022] [Indexed: 12/24/2022] Open
Abstract
The growing interest in the development of drugs that target the endocannabinoid system has extended to conditions that affect the audiovestibular pathway. The expression of cannabinoid (CB) receptors in that pathway has been widely demonstrated, indicating a therapeutic potential for drug development at this level. These medications may be beneficial for conditions such as noise-induced hearing loss, ototoxicity, or various forms of vertigo of central or peripheral origin. The therapeutic targets of interest include natural or synthetic compounds that act as CB1/CB2 receptor agonists/antagonists, and inhibitors of the endocannabinoid-degrading enzymes FAAH and MAGL. Furthermore, genetic variations implicated in the response to treatment and the development of related disorders such as epilepsy or migraine have been identified. Direct methods of administering these medications should be examined beyond the systemic strategy.
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Affiliation(s)
- Joaquin Guerra
- Neuro-Otolaryngology Unit, EuroEspes Biomedical Research Center, Institute of Medical Science and Genomic Medicine, Bergondo, Corunna, Spain,*Correspondence: Joaquin Guerra,
| | - Vinogran Naidoo
- Department of Neuroscience, International Center of Neuroscience and Genomic Medicine, EuroEspes Biomedical Research Center, Bergondo, Corunna, Spain
| | - Ramon Cacabelos
- Genomic Medicine, EuroEspes Biomedical Research Center, Institute of Medical Science and Genomic Medicine, Bergondo, Corunna, Spain
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Alhassan SO, Abdulrazaq Y, Odeh EO, Atawodi SEO. Crassocephalum rubens (Juss Ex Jacq) leaf diets ameliorate systemic oxidative stress and tissue damage in a Wistar rat model. J Food Biochem 2022; 46:e14491. [PMID: 36309952 DOI: 10.1111/jfbc.14491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 10/11/2022] [Accepted: 10/17/2022] [Indexed: 01/14/2023]
Abstract
The capacity of Crassocephalum rubens (Juss Ex Jacq) leaf to protect against systemic oxidative stress was evaluated in N-methyl-N-nitrosourea (MNU) - intoxicated rats fed at various inclusion rates for a period of twelve (12) weeks. Major organs and tissues were then assessed for indices of lipid peroxidation and oxidative stress. Crassocephalum rubens leaf significantly (p < .05) sustained the activities of superoxide dismutase and catalase with significant decrease in lipid peroxidation in MNU-intoxicated animals, particularly at 5% and 10% inlusion rates. The dietary inclusion also prevented significant changes in hematological parameters such as neutrophil and lymphocyte counts. It also reduced the severity of histologic damages such as necrosis, epithelial degeneration, inflammatory cell infiltration and other pathological changes to major organs. These results indicate that regular consumption of C. rubens leaf, prevents the deleterious biologic effects of the damaging reactive oxidative species (ROS). PRACTICAL APPLICATIONS: Crassocephalum rubens leaf has potential for development into a nutraceutical or functional food for chemoprevention and management of neurodegenerative diseases and other diseases associated with systemic oxidative stress, This is because its inclusion in the diet has attenuated lipid peroxidation, sustained the activity of antioxidant enzymes and mitigated deleterious changes in blood composition and tissue architecture resulting from exposure to a chemical carcinogen.
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Oleamide Reduces Mitochondrial Dysfunction and Toxicity in Rat Cortical Slices Through the Combined Action of Cannabinoid Receptors Activation and Induction of Antioxidant Activity. Neurotox Res 2022; 40:2167-2178. [PMID: 36069981 DOI: 10.1007/s12640-022-00575-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/12/2022] [Accepted: 08/30/2022] [Indexed: 12/31/2022]
Abstract
The potential treatment of neurodegenerative disorders requires the development of novel pharmacological strategies at the experimental level, such as the endocannabinoid-based therapies. The effects of oleamide (OEA), a fatty acid primary amide with activity on cannabinoid receptors, was tested against mitochondrial toxicity induced by the electron transport chain complex II inhibitor, 3-nitropropionic acid (3-NP), in rat cortical slices. OEA prevented the 3-NP-induced loss of mitochondrial function/cell viability at a concentration range of 5 nM-25 µM, and this protective effect was observed only when the amide was administered as pretreatment, but not as post-treatment. The preservation of mitochondrial function/cell viability induced by OEA in the toxic model induced by 3-NP was lost when the slices were pre-incubated with the cannabinoid receptor 1 (CB1R) selective inhibitor, AM281, or the cannabinoid receptor 2 (CB2R) selective inhibitor, JTE-907. The 3-NP-induced inhibition of succinate dehydrogenase (mitochondrial Complex II) activity was recovered by 25 nM OEA. The amide also prevented the increased lipid peroxidation and the changes in reduced/oxidized glutathione (GSH/GSSG) ratio induced by 3-NP. The cell damage induced by 3-NP, assessed as incorporation of cellular propidium iodide, was mitigated by OEA. Our novel findings suggest that the neuroprotective properties displayed by OEA during the early stages of damage to cortical cells involve the converging activation of CB1R and CB2R and the increase in antioxidant activity, which combined may emerge from the preservation of the functional integrity of mitochondria.
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Xu D, Xu C, Xue X, Xu Y, Zhao J, Huang T, Wang Z, Zhao Q, Zhou Z, Huang Y, Yu L, Wang H. Activation of cannabinoid receptor 2 attenuates Angiotensin II-induced atrial fibrillation via a potential NOX/CaMKII mechanism. Front Cardiovasc Med 2022; 9:968014. [PMID: 36312282 PMCID: PMC9616165 DOI: 10.3389/fcvm.2022.968014] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 09/29/2022] [Indexed: 11/13/2022] Open
Abstract
Background Atrial fibrillation (AF) is the most frequent arrythmia managed in clinical practice. Several mechanisms have been proposed to contribute to the occurrence and persistence of AF, in which oxidative stress plays a non-negligible role. The endocannabinoid system (ECS) is involved in a variety physiological and pathological processes. Cannabinoid receptor 1 (CB1R) and cannabinoid receptor 2 (CB2R) are expressed in the heart, and studies have shown that activating CB2R has a protective effect on the myocardium. However, the role of CB2R in AF is unknown. Materials and methods Angiotensin II (Ang II)-infused mice were treated with the CB2R agonist AM1241 intraperitoneally for 21 days. Atrial structural remodeling, AF inducibility, electrical transmission, oxidative stress and fibrosis were measured in mice. Results The susceptibility to AF and the level of oxidative stress were increased significantly in Ang II-infused mice. In addition, nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), NOX4, and oxidized Ca2+/calmodulin-dependent protein kinase II (ox-CaMKII) were highly expressed. More importantly, treatment with AM1241 activated CB2R, resulting in a protective effect. Conclusion The present study demonstrates that pharmacological activation of CB2R exerts a protective effect against AF via a potential NOX/CaMKII mechanism. CB2R is a potential therapeutic target for AF.
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Affiliation(s)
- Dengyue Xu
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China,Postgraduate College, China Medical University, Shenyang, Liaoning, China
| | - Chennian Xu
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Xiaodong Xue
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Yinli Xu
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Jikai Zhao
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Tao Huang
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Zhishang Wang
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Qiusheng Zhao
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Zijun Zhou
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Yuting Huang
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Liming Yu
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China,Liming Yu,
| | - Huishan Wang
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China,*Correspondence: Huishan Wang,
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Fallahi S, Bobak Ł, Opaliński S. Hemp in Animal Diets—Cannabidiol. Animals (Basel) 2022; 12:ani12192541. [PMID: 36230282 PMCID: PMC9559627 DOI: 10.3390/ani12192541] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/13/2022] [Accepted: 09/19/2022] [Indexed: 01/24/2023] Open
Abstract
In recent years, interest in hemp use has grown owing to its chemical and medicinal properties. Several parts of this plant, such as seeds, leaves, flowers, and stems are used in medicine, industry, and environmental preservation. Although there were legal restrictions on hemp exploitation in some countries due to the trace presence of THC as a psychoactive element, many countries have legalized it in recent years. Cannabidiol or CBD is a non-psychoactive phytocannabinoid that can activate the endocannabinoid system and its receptors in the central and peripheral nervous system in bodies of different species. Cannabidiol has anti-inflammatory, antioxidative, analgesic, and anti-depressant effects. This review investigates various aspects of cannabidiol use and its potential in animals and humans.
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Affiliation(s)
- Sepideh Fallahi
- Department of Environmental Hygiene and Animal Welfare, Wrocław University of Environmental and Life Sciences, 51-630 Wrocław, Poland
- Correspondence:
| | - Łukasz Bobak
- Department of Functional Food Products Development, Wrocław University of Environmental and Life Sciences, 51-630 Wrocław, Poland
| | - Sebastian Opaliński
- Department of Environmental Hygiene and Animal Welfare, Wrocław University of Environmental and Life Sciences, 51-630 Wrocław, Poland
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Protein Kinase N2 Reduces Hydrogen Peroxide-inducedDamage and Apoptosis in PC12 Cells by AntiOxidative Stress and Activation of the mTOR Pathway. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:2483669. [PMID: 36185087 PMCID: PMC9519335 DOI: 10.1155/2022/2483669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 09/02/2022] [Accepted: 09/09/2022] [Indexed: 11/17/2022]
Abstract
Objective To investigate the role and mechanism of protein kinase N2 (PKN2) in hydrogen peroxide (H2O2)-induced injury of PC12 cells. Method s. PC12 cells were transfected with lentivirus to knock down or overexpress PKN2 and then were treated with 300 μM H2O2 to establish a cell model of oxidative stress injury. The cell viability of PC12 cells in each group was determined by the CCK-8 method. Biochemical assays were used to measure reactive oxygen species (ROS), malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity. Western blot was used to detect the protein expressions of PKN2, caspase-3, cleaved-caspase-3, PARP, cleaved-PARP, p-mTOR, and mTOR in PC12 cells in each group. Results H2O2 treatment could significantly reduce PC12 cell viability and promote cell apoptosis and oxidative stress. PKN2 overexpression inhibited H2O2-induced apoptosis and oxidation damage by increasing PC12 cell viability, SOD activity, and p-mTOR protein expression, reducing intracellular ROS and MDA levels, and cleaved-caspase-3 and cleaved-PARP protein expression. Conclusion PKN2 overexpression can alleviate H2O2-induced oxidative stress injury and apoptosis in PC12 cells by activating the mTOR pathway.
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Drehmer E, Navarro-Moreno MÁ, Carrera-Juliá S, Moreno ML. A comparative study between olive oil and corn oil on oxidative metabolism. Food Funct 2022; 13:7157-7167. [PMID: 35699154 DOI: 10.1039/d2fo00919f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Fats are an important part of diet, but not all lipids have the same structure and chemical properties. Unsaturated fatty acids have one or more double bonds in their structure and can be monounsaturated or polyunsaturated, respectively. Most vegetable oils, such as olive oil and corn oil, contain significant amounts of these fatty acids. The presence of double bonds in the molecule of a fatty acid constitutes vulnerable sites for oxidation reactions generating lipid peroxides, potentially toxic compounds that can cause cellular damage. In response to this oxidative damage, aerobic organisms have intracellular enzymatic antioxidant defense mechanisms. The aim of the present investigation was to study comparatively the effects of control liquid diets, of a defined composition, containing olive oil or corn oil as a lipid source respectively of monounsaturated and polyunsaturated fatty acids, on the oxidative metabolism of rats. Rats were divided into three groups which received a control animal feed diet (A.F.), olive oil liquid diet (O.O) and corn oil liquid diet (C.O) for 30 days. It was observed that the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), increased in the liver and white fat tissue of rats fed with olive oil when compared to the corn oil group. However, in brown fat tissue and blood cells, the enzyme activities showed a tendency to decrease in the olive oil group. In addition, the effect of olive oil and corn oil on several glucose metabolism parameters (pyruvate, lactate, LDH, acetoacetate and beta-hydroxybutyrate) showed that corn oil impairs to a greater extent the cellular metabolism. All these results helped in concluding that some body tissues are more adversely affected than others by the administration of corn oil or olive oil, and their antioxidant defenses and cellular metabolism respond differently too.
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Affiliation(s)
- Eraci Drehmer
- Department of Health Sciences, Universidad Católica de Valencia "San Vicente Mártir", Valencia, Spain
| | | | - Sandra Carrera-Juliá
- Department of Nutrition and Dietetics, Universidad Católica de Valencia "San Vicente Mártir", Valencia, Spain
| | - Mari Luz Moreno
- Department of Human Physiology and Anatomy, Universidad Católica de Valencia "San Vicente Mártir", C/Ramiro de Maeztu, 14., 46900 Torrente, Valencia, Spain.
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Mishra RK, Selim A, Gowri V, Ahmad A, Nadeem A, Siddiqui N, Raza SS, Jayamurugan G, Khan R. Thiol-Functionalized Cellulose-Grafted Copper Oxide Nanoparticles for the Therapy of Experimental Colitis in Swiss Albino Mice. ACS Biomater Sci Eng 2022; 8:2088-2095. [PMID: 35452219 DOI: 10.1021/acsbiomaterials.2c00124] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Ulcerative colitis (UC) is a chronic inflammatory disease, which deleteriously affects the lower end of the gastrointestinal tract, i.e., the colon and the rectum. UC affects colonic inflammatory homeostasis and disrupts intestinal barrier functions. Intestinal tissue damage activates the immune system and collectively worsens the disease condition via the production of various cytokines. Ongoing therapeutics of UC have marked limitations like rapid clearance, extensive first-pass metabolism, poor drug absorption, very low solubility, bioavailability, etc. Because of these restrictions, the management of UC demands a rational approach that selectively delivers the drug at the site of action to overcome the therapeutic limiting factors. Metallic nanoparticles (NPs) have good therapeutic efficacy against colitis, but their uses are limited due to adverse effects on the biological system. In this study, we have used biocompatible thiol-functionalized cellulose-grafted copper oxide nanoparticles (C-CuI/IIO NPs) to treat UC. The metal NPs alleviated the colitis condition as evidenced by the colon length and observed physical parameters. Analysis of histopathology demonstrated the recovery of the colon architecture damaged by dextran sulfate sodium-induced colitis. Treatment with C-CuI/IIO NPs reduced the disintegration of goblet cells and the retainment of sulfomucin. Significant downregulation of inflammatory markers like MPO activity, as well as levels of nitrite and TNF-α, was found following C-CuI/IIO NP treatment. The observations from the study suggested that intrarectal treatment of colitis with cellulose-based C-CuI/IIO NPs successfully combated the intestinal inflammatory condition.
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Affiliation(s)
- Rakesh Kumar Mishra
- Chemical Biology Unit, Institute of Nano Science and Technology (INST), Knowledge City, Sector 81, Mohali, Punjab 140306, India
| | - Abdul Selim
- Energy and Environment Unit, Institute of Nano Science and Technology (INST), Knowledge City, Sector 81, Mohali, Punjab 140306, India
| | - Vijayendran Gowri
- Energy and Environment Unit, Institute of Nano Science and Technology (INST), Knowledge City, Sector 81, Mohali, Punjab 140306, India
| | - Anas Ahmad
- Julia McFarlane Diabetes Research Centre (JMDRC) and Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada
| | - Ahmed Nadeem
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Nahid Siddiqui
- Amity Institute of Biotechnology, Amity University, Noida 201303, India
| | - Syed Shadab Raza
- Laboratory for Stem Cell & Restorative Neurology, Department of Biotechnology, Era's Lucknow Medical College and Hospital, Sarfarazganj, Lucknow, Uttar Pradesh 226003, India
| | - Govindasamy Jayamurugan
- Energy and Environment Unit, Institute of Nano Science and Technology (INST), Knowledge City, Sector 81, Mohali, Punjab 140306, India
| | - Rehan Khan
- Chemical Biology Unit, Institute of Nano Science and Technology (INST), Knowledge City, Sector 81, Mohali, Punjab 140306, India
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Vasconcelos EM, Costa FC, Azevedo VAN, Paulino LRFM, Soares MD, Souza ALP, Carneiro VA, Brito GS, Catunda Júnior FEA, Silva JRV. Chemical composition and effects of Ocimum gratissimum essential oil (OGEO) on the expression of mRNA for antioxidant enzymes during in vitro culture of bovine ovarian secondary follicles. JOURNAL OF ESSENTIAL OIL RESEARCH 2022. [DOI: 10.1080/10412905.2022.2067256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- E. M. Vasconcelos
- Laboratory and Biotechnology and Physiology of Reproduction (LABIREP), Federal University of Ceara, Sobral, Brazil
| | - F. C. Costa
- Laboratory and Biotechnology and Physiology of Reproduction (LABIREP), Federal University of Ceara, Sobral, Brazil
| | - V. A. N. Azevedo
- Laboratory and Biotechnology and Physiology of Reproduction (LABIREP), Federal University of Ceara, Sobral, Brazil
| | - L. R. F. M. Paulino
- Laboratory and Biotechnology and Physiology of Reproduction (LABIREP), Federal University of Ceara, Sobral, Brazil
| | - M. D. Soares
- Laboratory and Biotechnology and Physiology of Reproduction (LABIREP), Federal University of Ceara, Sobral, Brazil
| | - A. L. P. Souza
- Laboratory and Biotechnology and Physiology of Reproduction (LABIREP), Federal University of Ceara, Sobral, Brazil
| | - V. A. Carneiro
- Laboratory of Biofilms and Antimicrobial Agents, Federal University of Ceará, Sobral, Brazil
| | - G. S. Brito
- Center for Exact, Natural and Technological Sciences, State University of the Tocantina Region of Maranhão, Imperatriz, Brazil
| | - F. E. A. Catunda Júnior
- Center for Exact, Natural and Technological Sciences, State University of the Tocantina Region of Maranhão, Imperatriz, Brazil
| | - J. R. V. Silva
- Laboratory and Biotechnology and Physiology of Reproduction (LABIREP), Federal University of Ceara, Sobral, Brazil
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Pawar HD, Mahajan UB, Nakhate KT, Agrawal YO, Patil CR, Meeran MFN, Sharma C, Ojha S, Goyal SN. Curcumin Protects Diabetic Mice against Isoproterenol-Induced Myocardial Infarction by Modulating CB2 Cannabinoid Receptors. Life (Basel) 2022; 12:624. [PMID: 35629293 PMCID: PMC9143027 DOI: 10.3390/life12050624] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/01/2022] [Accepted: 04/12/2022] [Indexed: 12/19/2022] Open
Abstract
Molecular docking revealed curcumin as a potent CB2 cannabinoid receptor (CB2R) agonist. Since CB2R is involved in cardioprotective functions, we explored its role in ameliorative actions of curcumin against myocardial damage triggered by isoproterenol in diabetic animals. Mice were kept on a high-fat diet (HFD) throughout the experiment (30 days). Following 7 days of HFD feeding, streptozotocin was administered (150 mg/kg, intraperitoneal) to induce diabetes. From day 11 to 30, diabetic mice received either curcumin (100 or 200 mg/kg/day, oral), CB2R antagonist AM630 (1 mg/kg/day, intraperitoneal) or both, with concurrent isoproterenol (150 mg/kg, subcutaneous) administration on day 28 and 29. Diabetic mice with myocardial infarction showed an altered hemodynamic pattern and lipid profile, reduced injury markers, antioxidants with increased lipid peroxidation in the myocardium, and elevated glucose and liver enzymes in the blood. Moreover, an increased pro-inflammatory markers, histological severity, myonecrosis, and edema were observed. Curcumin compensated for hemodynamic fluctuations, restored biochemical markers, preserved antioxidant capacity, decreased cytokines levels, and restored cardiac functionality. However, the AM630 pre-treatment attenuated the effects of curcumin. The data suggest the involvement of CB2R in the actions of curcumin such as in the prevention of myocardial stress and in the improvement of the normal status of the myocardial membrane associated with diabetes.
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Affiliation(s)
- Harshal D. Pawar
- Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, India; (H.D.P.); (U.B.M.); (C.R.P.)
| | - Umesh B. Mahajan
- Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, India; (H.D.P.); (U.B.M.); (C.R.P.)
| | - Kartik T. Nakhate
- Shri Vile Parle Kelavani Mandal’s Institute of Pharmacy, Dhule 424001, India; (K.T.N.); (Y.O.A.)
| | - Yogeeta O. Agrawal
- Shri Vile Parle Kelavani Mandal’s Institute of Pharmacy, Dhule 424001, India; (K.T.N.); (Y.O.A.)
| | - Chandragouda R. Patil
- Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, India; (H.D.P.); (U.B.M.); (C.R.P.)
| | - M. F. Nagoor Meeran
- Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates; (M.F.N.M.); (S.O.)
| | - Charu Sharma
- Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates;
| | - Shreesh Ojha
- Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates; (M.F.N.M.); (S.O.)
- Zayed Bin Sultan Center for Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
| | - Sameer N. Goyal
- Shri Vile Parle Kelavani Mandal’s Institute of Pharmacy, Dhule 424001, India; (K.T.N.); (Y.O.A.)
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Bagues A, López-Tofiño Y, Llorente-Berzal Á, Abalo R. Cannabinoid drugs against chemotherapy-induced adverse effects: focus on nausea/vomiting, peripheral neuropathy and chemofog in animal models. Behav Pharmacol 2022; 33:105-129. [PMID: 35045012 DOI: 10.1097/fbp.0000000000000667] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Although new drugs are being developed for cancer treatment, classical chemotherapeutic agents are still front-line therapies, despite their frequent association with severe side effects that can hamper their use. Cannabinoids may prevent or palliate some of these side effects. The aim of the present study is to review the basic research which has been conducted evaluating the effects of cannabinoid drugs in the treatment of three important side effects induced by classical chemotherapeutic agents: nausea and vomiting, neuropathic pain and cognitive impairment. Several published studies have demonstrated that cannabinoids are useful in preventing and reducing the nausea, vomits and neuropathy induced by different chemotherapy regimens, though other side effects can occur, such as a reduction of gastrointestinal motility, along with psychotropic effects when using centrally-acting cannabinoids. Thus, peripherally-acting cannabinoids and new pharmacological options are being investigated, such as allosteric or biased agonists. Additionally, due to the increase in the survival of cancer patients, there are emerging data that demonstrate an important cognitive deterioration due to chemotherapy, and because the cannabinoid drugs have a neuroprotective effect, they could be useful in preventing chemotherapy-induced cognitive impairment (as demonstrated through studies in other neurological disorders), but this has not yet been tested. Thus, although cannabinoids seem a promising therapeutic approach in the treatment of different side effects induced by chemotherapeutic agents, future research will be necessary to find pharmacological options with a safer profile. Moreover, a new line of research awaits to be opened to elucidate their possible usefulness in preventing cognitive impairment.
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Affiliation(s)
- Ana Bagues
- Área de Farmacología y Nutrición, Departamento de Ciencias Básicas de la Salud, Universidad Rey Juan Carlos (URJC), Alcorcón
- High Performance Research Group in Experimental Pharmacology (PHARMAKOM-URJC)
- Unidad Asociada I+D+i del Instituto de Química Médica (IQM), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - Yolanda López-Tofiño
- Área de Farmacología y Nutrición, Departamento de Ciencias Básicas de la Salud, Universidad Rey Juan Carlos (URJC), Alcorcón
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System NeuGut-URJC
| | - Álvaro Llorente-Berzal
- Pharmacology and Therapeutics, School of Medicine, National University of Ireland
- Centre for Pain Research and Galway Neuroscience Centre, NCBES, National University of Ireland, Galway, Ireland
| | - Raquel Abalo
- Área de Farmacología y Nutrición, Departamento de Ciencias Básicas de la Salud, Universidad Rey Juan Carlos (URJC), Alcorcón
- Unidad Asociada I+D+i del Instituto de Química Médica (IQM), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System NeuGut-URJC
- Grupo de Trabajo de Ciencias Básicas en Dolor y Analgesia de la Sociedad Española del Dolor, Madrid, Spain
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Essential Protective Role of Catalytically Active Antibodies (Abzymes) with Redox Antioxidant Functions in Animals and Humans. Int J Mol Sci 2022; 23:ijms23073898. [PMID: 35409256 PMCID: PMC8999700 DOI: 10.3390/ijms23073898] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 03/24/2022] [Accepted: 03/26/2022] [Indexed: 12/13/2022] Open
Abstract
During the life of aerobic organisms, the oxygen resulting from numerous reactions is converted into reactive oxygen species (ROS). Many ROS are dangerous due to their high reactivity; they are strong oxidants, and react with various cell components, leading to their damage. To protect against ROS overproduction, enzymatic and non-enzymatic systems are evolved in aerobic cells. Several known non-enzymatic antioxidants have a relatively low specific antioxidant activity. Superoxide dismutases, catalase, glutathione peroxidase, glutathione S-transferase, thioredoxin, and the peroxiredoxin families are the most important enzyme antioxidants. Artificial antibodies catalyzing redox reactions using different approaches have been created. During the past several decades, it has been shown that the blood and various biological fluids of humans and animals contain natural antibodies that catalyze different redox reactions, such as classical enzymes. This review, for the first time, summarizes data on existing non-enzymatic antioxidants, canonical enzymes, and artificial or natural antibodies (abzymes) with redox functions. Comparing abzymes with superoxide dismutase, catalase, peroxide-dependent peroxidase, and H2O2-independent oxidoreductase activities with the same activities as classical enzymes was carried out. The features of abzymes with the redox activities are described, including their exceptional diversity in the optimal pH values, dependency and independence on various metal ions, and the reaction rate constants for healthy donors and patients with different autoimmune diseases. The entire body of evidence indicates that abzymes with redox antioxidant activities existing in the blood for a long time compared to enzymes are an essential part of the protection system of humans and animals from oxidative stress.
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Xie MZ, Guo C, Dong JQ, Zhang J, Sun KT, Lu GJ, Wang L, Bo DY, Jiao LY, Zhao GA. Glyoxal damages human aortic endothelial cells by perturbing the glutathione, mitochondrial membrane potential, and mitogen-activated protein kinase pathways. BMC Cardiovasc Disord 2021; 21:603. [PMID: 34922451 PMCID: PMC8684178 DOI: 10.1186/s12872-021-02418-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 12/07/2021] [Indexed: 11/25/2022] Open
Abstract
Background Exposure to glyoxal, the smallest dialdehyde, is associated with several diseases; humans are routinely exposed to glyoxal because of its ubiquitous presence in foods and the environment. The aim of this study was to examine the damage caused by glyoxal in human aortic endothelial cells.
Methods Cell survival assays and quantitative fluorescence assays were performed to measure DNA damage; oxidative stress was detected by colorimetric assays and quantitative fluorescence, and the mitogen-activated protein kinase pathways were assessed using western blotting. Results Exposure to glyoxal was found to be linked to abnormal glutathione activity, the collapse of mitochondrial membrane potential, and the activation of mitogen-activated protein kinase pathways. However, DNA damage and thioredoxin oxidation were not induced by dialdehydes. Conclusions Intracellular glutathione, members of the mitogen-activated protein kinase pathways, and the mitochondrial membrane potential are all critical targets of glyoxal. These findings provide novel insights into the molecular mechanisms perturbed by glyoxal, and may facilitate the development of new therapeutics and diagnostic markers for cardiovascular diseases. Supplementary Information The online version contains supplementary material available at 10.1186/s12872-021-02418-3.
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Affiliation(s)
- Ming-Zhang Xie
- Department of Laboratory, First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453000, Henan, People's Republic of China.
| | - Chun Guo
- Henan Key Laboratory of Neural Regeneration (Henan Joint International Research Laboratory of Neurorestoratology for Senile Dementia), First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453000, Henan, People's Republic of China
| | - Jia-Qi Dong
- Department of Cardiovascular, First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453000, Henan, People's Republic of China
| | - Jie Zhang
- Department of Integrating Western and Chinese of Internal Medicine, First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453000, Henan, People's Republic of China
| | - Ke-Tao Sun
- Department of Laboratory, Zibo Central Hospital, Zibo, 255036, Shandong, People's Republic of China
| | - Guang-Jian Lu
- Department of Laboratory, First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453000, Henan, People's Republic of China
| | - Lei Wang
- Department of Laboratory, First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453000, Henan, People's Republic of China
| | - De-Ying Bo
- Department of Laboratory, First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453000, Henan, People's Republic of China
| | - Lu-Yang Jiao
- Department of Laboratory, First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453000, Henan, People's Republic of China.
| | - Guo-An Zhao
- Department of Cardiovascular, First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453000, Henan, People's Republic of China.
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Landerer S, Kalthoff S, Strassburg CP. UDP-glucuronosyltransferases mediate coffee-associated reduction of liver fibrosis in bile duct ligated humanized transgenic UGT1A mice. Hepatobiliary Surg Nutr 2021; 10:766-781. [PMID: 35004944 DOI: 10.21037/hbsn-20-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Accepted: 04/13/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Coffee consumption has been shown to reduce the risk of liver fibrosis and is capable of inducing human UDP-glucuronosyltransferase (UGT) 1A genes. UGT1A enzymes act as indirect antioxidants catalyzing the elimination of reactive metabolites, which in turn are potent initiators of profibrotic mechanisms. The aim of this study was to analyze the role of UGT1A genes as effectors of the protective properties of coffee in bile duct ligation (BDL) induced liver fibrosis. METHODS Fourteen days BDL with and without coffee pre- and co-treatment was performed in htgUGT1A-WT and htgUGT1A-SNP mice. Hepatic UGT1A mRNA expression levels, serum bilirubin and aminotransferase activities were determined. Liver fibrosis was assessed by collagen deposition, computational analysis of Sirius red tissue staining and expression of profibrotic marker genes. Oxidative stress was measured by hepatic peroxidase concentrations and immunofluorescence staining. RESULTS UGT1A transcription was differentially activated in the livers of htgUGT1A-WT mice after BDL, in contrast to a reduced or absent induction in the presence of SNPs. Co-treated (coffee + BDL) htgUGT1A-WT-mice showed significantly increased UGT1A expression and protein levels and a considerably higher induction compared to water drinking WT mice (BDL), whereas in co-treated htgUGT1A-SNP mice absolute expression levels remained below those observed in htgUGT1A-WT mice. Collagen deposition, oxidative stress and the expression of profibrotic markers inversely correlated with UGT1A expression levels in htgUGT1A-WT and SNP mice after BDL and coffee + BDL co-treatment. CONCLUSIONS Coffee exerts hepatoprotective and antioxidative effects via activation of UGT1A enzymes. Attenuated hepatic fibrosis as a result of coffee-mediated UGT1A induction during cholestasis was detected, while the protective action of coffee was lower in a common low-function UGT1A SNP haplotype present in 10% of the Caucasian population. This study suggests that coffee consumption might constitute a potential strategy to support the conventional treatment of cholestasis-related liver diseases.
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Affiliation(s)
- Steffen Landerer
- Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, Bonn, Germany
| | - Sandra Kalthoff
- Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, Bonn, Germany
| | - Christian P Strassburg
- Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, Bonn, Germany
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Boullon L, Abalo R, Llorente-Berzal Á. Cannabinoid Drugs-Related Neuroprotection as a Potential Therapeutic Tool Against Chemotherapy-Induced Cognitive Impairment. Front Pharmacol 2021; 12:734613. [PMID: 34867342 PMCID: PMC8632779 DOI: 10.3389/fphar.2021.734613] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 10/05/2021] [Indexed: 01/17/2023] Open
Abstract
In recent years, and particularly associated with the increase of cancer patients’ life expectancy, the occurrence of cancer treatment sequelae, including cognitive impairments, has received considerable attention. Chemotherapy-induced cognitive impairments (CICI) can be observed not only during pharmacological treatment of the disease but also long after cessation of this therapy. The lack of effective tools for its diagnosis together with the limited treatments currently available for alleviation of the side-effects induced by chemotherapeutic agents, demonstrates the need of a better understanding of the mechanisms underlying the pathology. This review focuses on the comprehensive appraisal of two main processes associated with the development of CICI: neuroinflammation and oxidative stress, and proposes the endogenous cannabinoid system (ECS) as a new therapeutic target against CICI. The neuroprotective role of the ECS, well described in other cognitive-related neuropathologies, seems to be able to reduce the activation of pro-inflammatory cytokines involved in the neuroinflammatory supraspinal processes underlying CICI. This review also provides evidence supporting the role of cannabinoid-based drugs in the modulation of oxidative stress processes that underpin cognitive impairments, and warrant the investigation of endocannabinoid components, still unknown, that may mediate the molecular mechanism behind this neuroprotective activity. Finally, this review points forward the urgent need of research focused on the understanding of CICI and the investigation of new therapeutic targets.
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Affiliation(s)
- Laura Boullon
- Pharmacology and Therapeutics, School of Medicine, National University of Ireland, Galway, Ireland
- Centre for Pain Research, National University of Ireland, Galway, Ireland
- Galway Neuroscience Centre, National University of Ireland, Galway, Ireland
| | - Raquel Abalo
- Área de Farmacología y Nutrición, Departamento de Ciencias Básicas de La Salud, Universidad Rey Juan Carlos (URJC), Alcorcón, Spain
- Unidad Asociada I+D+i Del Instituto de Química Médica (IQM), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System NeuGut-URJC, Madrid, Spain
- Working Group of Basic Sciences in Pain and Analgesia of the Spanish Pain Society (Grupo de Trabajo de Ciencias Básicas en Dolor y Analgesia de La Sociedad Española Del Dolor), Madrid, Spain
| | - Álvaro Llorente-Berzal
- Pharmacology and Therapeutics, School of Medicine, National University of Ireland, Galway, Ireland
- Centre for Pain Research, National University of Ireland, Galway, Ireland
- Galway Neuroscience Centre, National University of Ireland, Galway, Ireland
- *Correspondence: Álvaro Llorente-Berzal,
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Ebrahimi M, Norouzi P, Aazami H, Moosavi-Movahedi AA. Review on oxidative stress relation on COVID-19: Biomolecular and bioanalytical approach. Int J Biol Macromol 2021; 189:802-818. [PMID: 34418419 PMCID: PMC8372478 DOI: 10.1016/j.ijbiomac.2021.08.095] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 08/08/2021] [Accepted: 08/12/2021] [Indexed: 02/07/2023]
Abstract
COVID-19 disease has put life of people in stress worldwide from many aspects. Since the virus has mutated in absolutely short period of time the challenge to find a suitable vaccine has become harder. Infection to COVID-19, especially at severe life threatening states is highly dependent on the strength of the host immune system. This system is partially dependent on the balance between oxidative stress and antioxidant. Besides, this virus still has unknown mechanism of action companied by a probable commune period. From another hand, some reactive oxygen species (ROS) levels can be helpful on the state determination of the disease. Thus it could be possible to use modern bioanalytical techniques for their detection and determination, which could indicate the disease state at the golden time window since they have the potential to show whether specific DNA, RNA, enzymes and proteins are affected. This also could be used as a preclude study or a reliable pathway to define the best optimized time of cure beside effective medical actions. Herein, some ROS and their relation with SARS-CoV-2 virus have been considered. In addition, modern bioelectroanalytical techniques on this approach from quantitative and qualitative points of view have been reviewed.
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Affiliation(s)
- Mehrnaz Ebrahimi
- Center of Excellence in Electrochemistry, School of Chemistry, College of Science, University of Tehran, Tehran, Iran
| | - Parviz Norouzi
- Center of Excellence in Electrochemistry, School of Chemistry, College of Science, University of Tehran, Tehran, Iran.
| | - Hossein Aazami
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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Mizuno Y, Taguchi T. Fish Gelatin-Based Absorbable Dural Sealant with Anti-inflammatory Properties. ACS Biomater Sci Eng 2021; 7:4991-4998. [PMID: 34596382 DOI: 10.1021/acsbiomaterials.1c00734] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Cerebrospinal fluid (CSF) leakage from the dura mater during craniotomy is a common complication, which is associated with infection, meningitis, pneumocephalus, and delayed wound healing. In the present study, we developed an absorbable fish gelatin-based anti-inflammatory sealant for dura mater sealing to prevent CSF leakage. Gelatin derived from Alaska pollock (ApGltn) was modified with α-linolenic acid (ALA), an omega-3 fatty acid that exhibits anti-inflammatory properties, and cross-linked with a poly(ethylene glycol)-based cross-linker to develop ALA-ApGltn sealant (ALA-Seal). ALA-Seal demonstrated a higher storage modulus and tangent delta (tan δ) compared with those of the original ApGltn sealant (Org-Seal). The swelling ratio of ALA-Seal was markedly lower than that of DuraSeal, a commercially available dural sealant. Ex vivo burst strength measurements using porcine dura mater indicated that there was no significant difference between DuraSeal and ALA-Seal, despite ALA-Seal having an order of magnitude lower storage modulus. The anti-inflammatory properties of ALA-Seal, evaluated using brain microglial cells, were considerably higher than those of DuraSeal and Org-Seal, with a minimal adverse effect on cell viability. Therefore, compared to DuraSeal, ALA-Seal is a potential dural sealant with a lower swelling ratio, similar burst strength, and higher anti-inflammatory properties, which may prevent CSF leakage.
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Affiliation(s)
- Yosuke Mizuno
- Graduate School of Science and Technology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan.,Polymers and Biomaterials Field, Research Center for Functional Materials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan
| | - Tetsushi Taguchi
- Graduate School of Science and Technology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan.,Polymers and Biomaterials Field, Research Center for Functional Materials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan
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Rabino M, Mallia S, Castiglioni E, Rovina D, Pompilio G, Gowran A. The Endocannabinoid System and Cannabidiol: Past, Present, and Prospective for Cardiovascular Diseases. Pharmaceuticals (Basel) 2021; 14:ph14090936. [PMID: 34577636 PMCID: PMC8472406 DOI: 10.3390/ph14090936] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 09/09/2021] [Accepted: 09/13/2021] [Indexed: 12/18/2022] Open
Abstract
In the past, cannabis was commonly associated with mysticism and illegality. Fortunately, in recent years perspectives and discourses have changed. More prominence has been given to the rigorous scientific effort that led to the discovery of cannabis' many physiological actions and endogenous signalling mechanisms. The endocannabinoid system is a complex and heterogeneous pro-homeostatic network comprising different receptors with several endogenous ligands, numerous metabolic enzymes and regulatory proteins. Therefore, it is not surprising that alterations and dysfunctions of the endocannabinoid system are observed in almost every category of disease. Such high degree of pathophysiological involvement suggests the endocannabinoid system is a promising therapeutic target and prompted the translation of resurgent scientific findings into clinical therapies. Shifting attitudes toward cannabis also raised other matters such as increased patient awareness, prescription requests, self-medication, recreational use, recognition of new knowledge gaps, renewed scientific activity, and seemingly exponential growth of the cannabis industry. This review, following a general overview of cannabis and the endocannabinoid system, assiduously describes its role within the context of cardiovascular diseases, paying particular attention to the Janus influence that endocannabinoid system modulators can have on the cardiovascular system.
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Affiliation(s)
- Martina Rabino
- Unit of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino-IRCCS, 20138 Milan, Italy
| | - Sara Mallia
- Unit of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino-IRCCS, 20138 Milan, Italy
| | - Elisa Castiglioni
- Unit of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino-IRCCS, 20138 Milan, Italy
| | - Davide Rovina
- Unit of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino-IRCCS, 20138 Milan, Italy
| | - Giulio Pompilio
- Unit of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino-IRCCS, 20138 Milan, Italy
- Department of Cardiac Surgery, Centro Cardiologico Monzino-IRCCS, 20138 Milan, Italy
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20138 Milan, Italy
| | - Aoife Gowran
- Unit of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino-IRCCS, 20138 Milan, Italy
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Wang C, Liu Y, Wang H, Gao F, Guan X, Shi B. Maternal Exposure to Oxidized Soybean Oil Impairs Placental Development by Modulating Nutrient Transporters in a Rat Model. Mol Nutr Food Res 2021; 65:e2100301. [PMID: 34289236 DOI: 10.1002/mnfr.202100301] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 06/13/2021] [Indexed: 01/07/2023]
Abstract
INTRODUCTION As an exogenous food contaminant, dietary oxidized lipid impairs growth and development, and triggers chronic diseases in humans or animals. This study explores the effects of soybean oil with different oxidative degree on the placental injury of gestational rats. METHODS AND RESULTS Thirty-two female adult rats are randomly assigned to four groups. The control group is fed the purified diet with fresh soybean oil (FSO), and the treatment groups are fed purified diets with lipid content replaced by oxidized soybean oil (OSO) at 200, 400, and 800 mEqO2 kg-1 from conception until delivery. On day 20 of gestation, OSO decreased placental and embryonic weights as the oxidative degree increased linearly and quadratically. The expression of Bax showed a linear increase, and Bcl-2 decreased as the oxidative degree increased. The expression of Fosl1 and Esx1 is linearly and quadratically decreased in OSO-treated groups than FSO group. OSO decreased the level of IL-10 but increased expression of IL-1β in placenta and plasma. OSO remarkably upregulates levels of Fatp1 and Glut1 and decreases expression of Snat2 and Glut3. CONCLUSION OSO aggravates placental injury by modulating nutrient transporters and apoptosis-related genes, impedes placental growth and development, and ultimately leads to the decrease of fetal weight.
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Affiliation(s)
- Chuanqi Wang
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Yang Liu
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Huiting Wang
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Feng Gao
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Xin Guan
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Baoming Shi
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, People's Republic of China
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Liu Y, Cong L, Han C, Li B, Dai R. Recent Progress in the Drug Development for the Treatment of Alzheimer's Disease Especially on Inhibition of Amyloid-peptide Aggregation. Mini Rev Med Chem 2021; 21:969-990. [PMID: 33245270 DOI: 10.2174/1389557520666201127104539] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 08/25/2020] [Accepted: 09/14/2020] [Indexed: 11/22/2022]
Abstract
As the world 's population is aging, Alzheimer's disease (AD) has become a big concern since AD has started affecting younger people and the population of AD patients is increasing worldwide. It has been revealed that the neuropathological hallmarks of AD are typically characterized by the presence of neurotoxic extracellular amyloid plaques in the brain, which are surrounded by tangles of neuronal fibers. However, the causes of AD have not been completely understood yet. Currently, there is no drug to effectively prevent AD or to completely reserve the symptoms in the patients. This article reviews the pathological features associated with AD, the recent progress in research on the drug development to treat AD, especially on the discovery of natural product derivatives to inhibit Aβ peptide aggregation as well as the design and synthesis of Aβ peptide aggregation inhibitors to treat AD.
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Affiliation(s)
- Yuanyuan Liu
- Advanced Research Institute of Multidisciplinary Science, Beijing Institute of Technology, Beijing, 100081, China
| | - Lin Cong
- Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, School of Life Science, Beijing Institute of Technology, Beijing, 10081, China
| | - Chu Han
- Advanced Research Institute of Multidisciplinary Science, Beijing Institute of Technology, Beijing, 100081, China
| | - Bo Li
- Advanced Research Institute of Multidisciplinary Science, Beijing Institute of Technology, Beijing, 100081, China
| | - Rongji Dai
- Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, School of Life Science, Beijing Institute of Technology, Beijing, 10081, China
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Biernacki M, Jastrząb A, Skrzydlewska E. Changes in Hepatic Phospholipid Metabolism in Rats under UV Irradiation and Topically Treated with Cannabidiol. Antioxidants (Basel) 2021; 10:1157. [PMID: 34439405 PMCID: PMC8388943 DOI: 10.3390/antiox10081157] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/16/2021] [Accepted: 07/19/2021] [Indexed: 01/02/2023] Open
Abstract
The liver is a key metabolic organ that is particularly sensitive to environmental factors, including UV radiation. As UV radiation induces oxidative stress and inflammation, natural compounds are under investigation as one method to counteract these consequences. The aim of this study was to assess the effect of topical application of phytocannabinoid-cannabidiol (CBD) on the skin of nude rats chronically irradiated with UVA/UVB, paying particular attention to its impact on the liver antioxidants and phospholipid metabolism. The results of this study indicate that CBD reaches the rat liver where it is then metabolized into decarbonylated cannabidiol, 7-hydroxy-cannabidiol and cannabidiol-glucuronide. CBD increased the levels of GSH and vitamin A after UVB radiation. Moreover, CBD prevents the increase of 4-hydroxynonenal and 8-iso-prostaglandin-F2α levels in UVA-irradiated rats. As a consequence of reductions in phospholipase A2 and cyclooxygenases activity following UV irradiation, CBD upregulates the level of 2-arachidonoylglycerol and downregulates prostaglandin E2 and leukotriene B4. Finally, CBD enhances decreased level of 15-deoxy-Δ-12,14-prostaglandin J2 after UVB radiation and 15-hydroxyeicosatetraenoic acid after UVA radiation. These data show that CBD applied to the skin prevents ROS- and enzyme-dependent phospholipid metabolism in the liver of UV-irradiated rats, suggesting that it may be used as an internal organ protector.
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Affiliation(s)
| | | | - Elżbieta Skrzydlewska
- Department of Analytical Chemistry, Medical University of Bialystok, A. Mickiewicza 2D, 15-222 Bialystok, Poland; (M.B.); (A.J.)
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Shared Biological Pathways between Antipsychotics and Omega-3 Fatty Acids: A Key Feature for Schizophrenia Preventive Treatment? Int J Mol Sci 2021; 22:ijms22136881. [PMID: 34206945 PMCID: PMC8269187 DOI: 10.3390/ijms22136881] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 06/18/2021] [Accepted: 06/23/2021] [Indexed: 12/25/2022] Open
Abstract
Schizophrenia typically emerges during adolescence, with progression from an ultra-high risk state (UHR) to the first episode of psychosis (FEP) followed by a chronic phase. The detailed pathophysiology of schizophrenia and the factors leading to progression across these stages remain relatively unknown. The current treatment relies on antipsychotics, which are effective for FEP and chronic schizophrenia but ineffective for UHR patients. Antipsychotics modulate dopaminergic and glutamatergic neurotransmission, inflammation, oxidative stress, and membrane lipids pathways. Many of these biological pathways intercommunicate and play a role in schizophrenia pathophysiology. In this context, research of preventive treatment in early stages has explored the antipsychotic effects of omega-3 supplementation in UHR and FEP patients. This review summarizes the action of omega-3 in various biological systems involved in schizophrenia. Similar to antipsychotics, omega-3 supplementation reduces inflammation and oxidative stress, improves myelination, modifies the properties of cell membranes, and influences dopamine and glutamate pathways. Omega-3 supplementation also modulates one-carbon metabolism, the endocannabinoid system, and appears to present neuroprotective properties. Omega-3 has little side effects compared to antipsychotics and may be safely prescribed for UHR patients and as an add-on for FEP patients. This could to lead to more efficacious individualised treatments, thus contributing to precision medicine in psychiatry.
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Bielawiec P, Harasim-Symbor E, Sztolsztener K, Konstantynowicz-Nowicka K, Chabowski A. Attenuation of Oxidative Stress and Inflammatory Response by Chronic Cannabidiol Administration Is Associated with Improved n-6/n-3 PUFA Ratio in the White and Red Skeletal Muscle in a Rat Model of High-Fat Diet-Induced Obesity. Nutrients 2021; 13:nu13051603. [PMID: 34064937 PMCID: PMC8151284 DOI: 10.3390/nu13051603] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 04/27/2021] [Accepted: 05/07/2021] [Indexed: 12/28/2022] Open
Abstract
The consumption of fatty acids has increased drastically, exceeding the nutritional requirements of an individual and leading to numerous metabolic disorders. Recent data indicate a growing interest in using cannabidiol (CBD) as an agent with beneficial effects in the treatment of obesity. Therefore, our aim was to investigate the influence of chronic CBD administration on the n-6/n-3 polyunsaturated fatty acids (PUFAs) ratio in different lipid fractions, inflammatory pathway and oxidative stress parameters in the white and red gastrocnemius muscle. All the designed experiments were performed on Wistar rats fed a high-fat diet (HFD) or a standard rodent diet for seven weeks and subsequently injected with CBD (10 mg/kg once daily for two weeks) or its vehicle. Lipid content and oxidative stress parameters were assessed using gas-liquid chromatography (GLC), colorimetric and/or immunoenzymatic methods, respectively. The total expression of proteins of an inflammatory pathway was measured by Western blotting. Our results revealed that fatty acids (FAs) oversupply is associated with an increasing oxidative stress and inflammatory response, which results in an excessive accumulation of FAs, especially of n-6 PUFAs, in skeletal muscles. We showed that CBD significantly improved the n-6/n-3 PUFA ratio and shifted the equilibrium towards anti-inflammatory n-3 PUFAs, particularly in the red gastrocnemius muscle. Additionally, CBD prevented generation of lipid peroxidation products and attenuated inflammatory response in both types of skeletal muscle. In summary, the results mentioned above indicate that CBD presents potential therapeutic properties with respect to the treatment of obesity and related disturbances.
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Pinky PD, Majrashi M, Fujihashi A, Bloemer J, Govindarajulu M, Ramesh S, Reed MN, Moore T, Suppiramaniam V, Dhanasekaran M. Effects of prenatal synthetic cannabinoid exposure on the cerebellum of adolescent rat offspring. Heliyon 2021; 7:e06730. [PMID: 33912711 PMCID: PMC8066425 DOI: 10.1016/j.heliyon.2021.e06730] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 11/19/2020] [Accepted: 04/01/2021] [Indexed: 11/25/2022] Open
Abstract
Cannabis is the most commonly used illicit drug worldwide. Recently, cannabis use among young pregnant women has greatly increased. However, prenatal cannabinoid exposure leads to long-lasting cognitive, motor, and behavioral deficits in the offspring and alterations in neural circuitry through various mechanisms. Although these effects have been studied in the hippocampus, the effects of prenatal cannabinoid exposure on the cerebellum are not well elucidated. The cerebellum plays an important role in balance and motor control, as well as cognitive functions such as attention, language, and procedural memories. The aim of this study was to investigate the effects of prenatal cannabinoid exposure on the cerebellum of adolescent offspring. Pregnant rats were treated with synthetic cannabinoid agonist WIN55,212-2, and the offspring were evaluated for various cerebellar markers of oxidative stress, mitochondrial function, and apoptosis. Additionally, signaling proteins associated with glutamate dependent synaptic plasticity were examined. Administration of WIN55,212-2 during pregnancy altered markers of oxidative stress by significantly reducing oxidative stress and nitrite content. Mitochondrial Complex I and Complex IV activities were also enhanced following prenatal cannabinoid exposure. With regard to apoptosis, pP38 levels were significantly increased, and proapoptotic factor caspase-3 activity, pERK, and pJNK levels were significantly decreased. CB1R and GluA1 levels remained unchanged; however, GluN2A was significantly reduced. There was a significant decrease in MAO activity although tyrosine hydroxylase activity was unaltered. Our study indicates that the effects of prenatal cannabinoid exposure on the cerebellum are unique compared to other brain regions by enhancing mitochondrial function and promoting neuronal survival. Further studies are required to evaluate the mechanisms by which prenatal cannabinoid exposure alters cerebellar processes and the impact of these alterations on behavior.
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Affiliation(s)
- Priyanka D. Pinky
- Department of Drug Discovery and Development, Auburn University, Auburn, AL, USA
- Center for Neuroscience Initiatives, Auburn University, Auburn, AL, USA
| | - Mohammed Majrashi
- Department of Drug Discovery and Development, Auburn University, Auburn, AL, USA
| | - Ayaka Fujihashi
- Department of Drug Discovery and Development, Auburn University, Auburn, AL, USA
| | - Jenna Bloemer
- Department of Drug Discovery and Development, Auburn University, Auburn, AL, USA
- Department of Biomedical and Pharmaceutical Sciences, Touro College of Pharmacy, New York, NY, USA
| | - Manoj Govindarajulu
- Department of Drug Discovery and Development, Auburn University, Auburn, AL, USA
- Center for Neuroscience Initiatives, Auburn University, Auburn, AL, USA
| | - Sindhu Ramesh
- Department of Drug Discovery and Development, Auburn University, Auburn, AL, USA
- Center for Neuroscience Initiatives, Auburn University, Auburn, AL, USA
| | - Miranda N. Reed
- Department of Drug Discovery and Development, Auburn University, Auburn, AL, USA
- Center for Neuroscience Initiatives, Auburn University, Auburn, AL, USA
| | - Timothy Moore
- Department of Drug Discovery and Development, Auburn University, Auburn, AL, USA
- Center for Neuroscience Initiatives, Auburn University, Auburn, AL, USA
| | - Vishnu Suppiramaniam
- Department of Drug Discovery and Development, Auburn University, Auburn, AL, USA
- Center for Neuroscience Initiatives, Auburn University, Auburn, AL, USA
| | - Muralikrishnan Dhanasekaran
- Department of Drug Discovery and Development, Auburn University, Auburn, AL, USA
- Center for Neuroscience Initiatives, Auburn University, Auburn, AL, USA
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Chavira-Ramos K, Orozco-Morales M, Karasu Ç, Tinkov AA, Aschner M, Santamaría A, Colín-González AL. URB597 Prevents the Short-Term Excitotoxic Cell Damage in Rat Cortical Slices: Role of Cannabinoid 1 Receptors. Neurotox Res 2021; 39:146-155. [PMID: 33141426 DOI: 10.1007/s12640-020-00301-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 10/19/2020] [Accepted: 10/20/2020] [Indexed: 01/21/2023]
Abstract
Endocannabinoid-based therapies constitute an emerging tool for the potential treatment of neurodegenerative disorders, requiring characterization at the experimental level. The effects of URB597, an inhibitor of the fatty acid amide hydrolase (FAAH), were tested against the quinolinic acid (QUIN)-induced early toxic effects in rat cortical slices, and compared with those effects exerted by the endocannabinoid anandamide (AEA). URB597 prevented the QUIN-induced loss of mitochondrial function/cell viability and lipid peroxidation, while reduced necrosis, and to a lesser extent, apoptosis. The protective effects of URB597 were mediated by activation of cannabinoid receptor 1 (CB1r), as evidenced by their inhibition by the selective CB1r antagonist AM281. Similar effects were observed when testing AEA against QUIN toxicity. Our findings demonstrate the neuroprotective properties of URB597 during the early stages of excitotoxic damage to cortical tissue, suggesting that these properties are mediated by FAAH inhibition, and might be linked to the protective effects of AEA, or the combination of endocannabinoids.
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Affiliation(s)
- Karla Chavira-Ramos
- Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, S.S.A., 14269, Mexico City, Mexico
| | - Mario Orozco-Morales
- Laboratorio de Medicina Personalizada, Instituto Nacional de Cancerología, S.S.A., 14080, Mexico City, Mexico
| | - Çimen Karasu
- Cellular Stress Response and Signal Transduction Research Laboratory, Faculty of Medicine, Department of Medical Pharmacology, Gazi University, Beşevler, 06500, Ankara, Turkey
| | - Alexey A Tinkov
- IM Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
- Yaroslavl State University, Yaroslavl, Russia
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 11354, USA
| | - Abel Santamaría
- Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, S.S.A., 14269, Mexico City, Mexico.
| | - Ana Laura Colín-González
- Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, S.S.A., 14269, Mexico City, Mexico
- Banco de Tumores, Instituto Nacional de Cancerología, S.S.A., 14080, Mexico City, Mexico
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