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Megahed A, Gadalla H, Filimban WA, Albukhari TA, Sembawa H, Bagadood RM, Sindi G, Abdelhamid FM, El-Boshy ME, Risha EF. Hesperidin ameliorates thioacetamide-induced liver fibrosis via antioxidative and anti-inflammatory mechanisms targeting TGF-β/α-SMA pathways in rats. Int J Immunopathol Pharmacol 2024; 38:3946320241309004. [PMID: 39707862 DOI: 10.1177/03946320241309004] [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: 12/23/2024] Open
Abstract
Our study intended to explore Hesp antioxidant and anti-inflammatory effects against TAA hepatic fibrosis in rats. Hesperidin (Hesp), is a pharmacologically active flavonoid, found abundantly in citrus species. Our present research attempts to inspect the potential hepatoprotective role of Hesp against thioacetamide (TAA)-induced hepatic fibrosis. Thirty-two male albino rats were split up into four equal groups, each with eight rats: Cont group was treated with ip saline. Every other day, the TAA group was injected 100 mg/kg BW ip TAA, Hesp group received every day oral Hesp 200 mg/kg BW as well as TAA + Hesp group received both therapies (TAA, Hesp) for eight successive weeks. Hesp in TAA treated group reduces ALT, AST, and ALP activities, total, direct bilirubin, total cholesterol, and triglycerides, meanwhile TP, Alb, globulin, A/G ratio levels were insignificantly differed. The antioxidant capacity of Hesp was pronounced by a marked reduction in MDA level. While the antioxidant markers (SOD, CAT, GSH) were insignificantly changed after Hesp treatment. A strong significant correlation in treated rats between fibrosis score and CD34 and FGF23 gene expression. Liver sections from dual-treated rats showed a moderately decreased hepatic lesion and the dense, bluish-stained fibrous tissue by Masson's trichrome. Elevated gene expressions of CD34 and FGF23 after TAA hepatotoxicity were diminished by the antifibrotic effect of Hesp. Also, immunohistochemical expression showed reduction of TGF-β and α-SMA in hepatocytes in the dual therapy group. Hesp possesses a potent antioxidant, and antifibrotic activities against TAA induced hepatic fibrosis by modulating TGF-β/α-SMA pathways.
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Affiliation(s)
- Aya Megahed
- Clinical Pathology Department, Veterinary Medicine Faculty, University of Mansoura, Mansoura, Egypt
| | - Hossam Gadalla
- Clinical Pathology Department, Veterinary Medicine Faculty, University of Mansoura, Mansoura, Egypt
| | - Waheed A Filimban
- Pathology Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Talat A Albukhari
- Department of Hematology and Immunology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Hatem Sembawa
- Department of Surgery, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Rehab M Bagadood
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Ghadir Sindi
- Clinical Laboratory Sciences Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia
| | - Fatma M Abdelhamid
- Clinical Pathology Department, Veterinary Medicine Faculty, University of Mansoura, Mansoura, Egypt
| | - Mohamed E El-Boshy
- Clinical Pathology Department, Veterinary Medicine Faculty, University of Mansoura, Mansoura, Egypt
| | - Engy F Risha
- Clinical Pathology Department, Veterinary Medicine Faculty, University of Mansoura, Mansoura, Egypt
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Megahed A, Gadalla H, Abdelhamid FM, Almehmadi SJ, Khan AA, Albukhari TA, Risha EF. Vitamin D Ameliorates the Hepatic Oxidative Damage and Fibrotic Effect Caused by Thioacetamide in Rats. Biomedicines 2023; 11:biomedicines11020424. [PMID: 36830960 PMCID: PMC9953330 DOI: 10.3390/biomedicines11020424] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/26/2023] [Accepted: 01/28/2023] [Indexed: 02/05/2023] Open
Abstract
Vitamin D3 (VD3) is a sunshine hormone that regulates cellular proliferation, differentiation, apoptosis, and angiogenesis related to liver parenchyma. We used a thioacetamide (TAA)-induced hepatic fibrosis rat model in our study to investigate the beneficial roles of VD3 to overcome extensive liver fibrosis. Randomly, four equal groups (eight rats per group) underwent therapy for eight successive weeks: a control group, a group treated with TAA 100 mg/kg BW IP every other day, a group treated with VD3 1000 IU/kg BW IM every day, and a TAA+VD group treated with both therapies. Treatment with VD3 after TAA-induced hepatic fibrosis was found to alleviate elevated liver function measures by decreasing ALT, AST, and ALP activity; decreasing total bilirubin, direct bilirubin, cholesterol, and triglyceride levels; and increasing glucose and 25[OH]D3. Rats treated with VD3 showed marked decreases in MDA and increased SOD, CAT, and GSH levels. In addition, CD34 and FGF23 gene expressions were reduced after dual therapy. Liver sections from the TAA+VD group showed markedly decreased hepatic lesions, and Masson's trichrome stain showed a marked decrease in dense bluish-stained fibrous tissue. The immunohistochemical expression of TGF-β and α-SMA showed markedly decreased positive brown cytoplasmic expression in a few hepatocytes, clarifying the antifibrotic effect of VD3 in hepatic fibrosis. In conclusion, VD3 alleviates hepatotoxicity and fibrosis caused by TAA.
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Affiliation(s)
- Aya Megahed
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansour 35516, Egypt
| | - Hossam Gadalla
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansour 35516, Egypt
| | - Fatma M. Abdelhamid
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansour 35516, Egypt
| | - Samah J. Almehmadi
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia
| | - Anmar A. Khan
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia
| | - Talat A. Albukhari
- Department of Immunology and Hematology, Faculty of Medicine, Umm Al-Qura University, Makkah P.O. Box 7607, Saudi Arabia
| | - Engy F. Risha
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansour 35516, Egypt
- Correspondence: ; Tel.: +20-120-534-8354
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Wang W, Chen Y, Kuo C, Tsai J, Hsu F, Chung J, Pan P. DNA
damage and
NF‐κB
inactivation implicate glycyrrhizic acid‐induced
G
1
phase arrest in hepatocellular carcinoma cells. J Food Biochem 2022; 46:e14128. [DOI: 10.1111/jfbc.14128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Revised: 02/11/2022] [Accepted: 02/18/2022] [Indexed: 11/29/2022]
Affiliation(s)
- Wei‐Shu Wang
- Department of Medicine National Yang Ming Chiao Tung University Hospital Yilan Taiwan
- School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan
| | - Yu‐Shan Chen
- Department of Radiation Oncology Show Chwan Memorial Hospital Changhua Taiwan
| | - Chen‐Yu Kuo
- Division of Gastroenterology, Department of Medicine National Yang Ming Chiao Tung University Hospital Yilan Taiwan
| | - Jai‐Jen Tsai
- School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan
- Division of Gastroenterology, Department of Medicine National Yang Ming Chiao Tung University Hospital Yilan Taiwan
- Department of Nursing Cardinal Tien Junior College of Healthcare and Management New Taipei City Taiwan
| | - Fei‐Ting Hsu
- Department of Biological Science and Technology China Medical University Taichung Taiwan
| | - Jing‐Gung Chung
- Department of Biological Science and Technology China Medical University Taichung Taiwan
- Department of Medical Laboratory and Biotechnology Asia University Taichung Taiwan
| | - Po‐Jung Pan
- School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan
- Department of Physical Medicine and Rehabilitation National Yang Ming Chiao Tung University Hospital Yilan Taiwan
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El-Fadaly AA, Afifi NA, El-Eraky W, Salama A, Abdelhameed MF, El-Rahman SSA, Ramadan A. Fisetin alleviates thioacetamide-induced hepatic fibrosis in rats by inhibiting Wnt/β-catenin signaling pathway. Immunopharmacol Immunotoxicol 2022; 44:355-366. [PMID: 35255766 DOI: 10.1080/08923973.2022.2047198] [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: 11/05/2022]
Abstract
BACKGROUND Liver fibrosis is a chronic wound-healing response to liver injury of various origins and represents a major health problem. OBJECTIVE The current study endeavored to investigate the repressing effect of fisetin on hepatic fibrosis induced by thioacetamide (TAA) in rats. MATERIALS AND METHODS Rats were injected with TAA (200 mg/kg) intraperitoneally twice per week for 6 weeks to induce liver fibrosis. Fisetin (50 and 100 mg/kg/day) or silymarin (50 mg/kg/day) were given orally on a daily basis along with TAA. Liver function parameters, oxidative stress, inflammatory and fibrogenic biomarkers as well as wnt3a, β-catenin, glycogen synthase kinase 3 (GSK-3β) and cyclin D1 were estimated. Histoapthological and immunohistochemical examinations were performed. RESULTS Fisetin restored normal liver functions, increased reduced glutathione (GSH) level and decreased malondialdehyde (MDA), as well as inflammatory biomarkers including; tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6). Additionally, it lessened transforming growth factor β1 (TGF-β1), collagen I and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels as well as elevated matrix metalloproteinase-9 (MMP-9) hepatic content. Furthermore, fisetin significantly suppressed wnt3a gene expression associated with decreased β-catenin and increased GSK-3β levels. Moreover, fisetin decreased the progress of histologic hepatic fibroplasia and diminished hepatic expression of α-SMA and cyclin D1. CONCLUSION Fisetin curbed liver fibrosis and exhibited superior activity over silymarin through inhibition of hepatic stellate cells (HSCs) activation and proliferation via suppressing the Wnt/β-catenin pathway, modulating MMP-9 and TIMP-1, and inhibiting multiple profibrogenic factors, besides its antioxidant and anti-inflammatory effects. Therefore, fisetin is a promising therapeutic candidate for hepatic fibrosis.
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Affiliation(s)
| | - Nehal A Afifi
- Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Wafaa El-Eraky
- Department of Pharmacology, National Research Centre, Cairo, Egypt
| | - Abeer Salama
- Department of Pharmacology, National Research Centre, Cairo, Egypt
| | | | - Sahar S Abd El-Rahman
- Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - A Ramadan
- Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
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Song Z, Zhu M, Wu J, Yu T, Chen Y, Ye X, Li S, Xu N. Fucoidans from Cucumaria frondosa ameliorate renal interstitial fibrosis via inhibition of the PI3K/Akt/NF-κB signaling pathway. Food Funct 2022; 13:1168-1179. [PMID: 35018932 DOI: 10.1039/d1fo03067a] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
The effects of Cucumaria frondosa polysaccharides (CFPs) on renal interstitial fibrosis by regulating the phosphatidylinositol-3-hydroxykinase/protein kinase-B/nuclear factor-κB (PI3K/AKT/NF-κB) signaling pathway were investigated in vivo and in vitro in this research. The common unilateral urethral obstruction (UUO) model was used to examine the renoprotective effect and its mechanism in vivo. Compared to the UUO group, CFP administration could ameliorate renal function, inhibit inflammation and fibrosis, and reduce the deposition of the extracellular matrix and epithelial-mesenchymal transition. Mechanistic results indicated that CFPs could inhibit the expression of the total protein of PI3K and the conversion of the AKT and NF-κB p65 phosphorylated proteins, thereby inhibiting the transduction of the PI3K/AKT/NF-κB pathway. In addition, CFP treatment could improve inflammation and fibrosis in HK-2 cells induced by TGF-β1, and its in vitro mechanism was also verified to inhibit the PI3K/Akt/NF-κB signaling pathway. Overall, these results showed that CFP could alleviate renal interstitial fibrosis related to the PI3K/AKT/NF-κB signaling pathway.
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Affiliation(s)
- Zhuoyue Song
- Clinical Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, PR China.
| | - Mengru Zhu
- Clinical Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, PR China.
| | - Jun Wu
- School of Chinese Medicine, Shandong College of Traditional Chinese Medicine, Yantai 264199, Shandong, PR China
| | - Tian Yu
- Clinical Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, PR China.
| | - Yao Chen
- Clinical Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, PR China.
| | - Xianying Ye
- Clinical Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, PR China.
| | - Shijie Li
- Clinical Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, PR China.
| | - Nenggui Xu
- Clinical Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, PR China.
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Heidari S, Mehri S, Hosseinzadeh H. The genus Glycyrrhiza (Fabaceae family) and its active constituents as protective agents against natural or chemical toxicities. Phytother Res 2021; 35:6552-6571. [PMID: 34414608 DOI: 10.1002/ptr.7238] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 06/28/2021] [Accepted: 07/27/2021] [Indexed: 12/27/2022]
Abstract
Licorice is the dried roots and rhizomes of various species of the genus Glycyrrhiza (Fabaceae) that have been used in folk medicine from ancient times. Many important research projects have established several beneficial effects for this medicinal herb, including antiinflammatory, antimicrobial, antiviral, antiprotozoal, antioxidant, antihyperglycemic, antihyperlipidemic, hepatoprotective, and neuroprotective. Licorice contains important bioactive components, such as glycyrrhizin (glycyrrhizic, glycyrrhizinic acid), liquiritigenin, liquiritin, and glycyrrhetinic acid. The protective effects of licorice and its main chemical components against toxins and toxicants in several organs including the brain, heart, liver, kidney, and lung have been shown. In this comprehensive review article, the protective effects of these constituents against natural, industrial, environmental, and chemical toxicities with attention on the cellular and molecular mechanism are introduced. Also, it has been revealed that this plant and its main compounds can inhibit the toxicity of different toxins by the antioxidant, antiinflammatory, and anti-apoptotic properties as well as the modulation of Inhibitor of kappaB kinase (IKK), Extracellular signal-regulated protein kinase1/2 (ERK1/2), p38, inducible nitric oxide synthase, and nuclear factor-κB (NF-κB) signaling pathways. More high-quality investigations in both experimental and clinical studies need to firmly establish the efficacy of licorice and its main constituents against toxic agents.
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Affiliation(s)
- Somaye Heidari
- Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran.,Toxicology and Addiction Research Center, Zabol University of Medical Sciences, Zabol, Iran
| | - Soghra Mehri
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Pharmacodynamics and Toxicology, School pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Hosseinzadeh
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Pharmacodynamics and Toxicology, School pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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7
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Lanjekar KJ, Rathod VK. Application of Ultrasound and Natural Deep Eutectic Solvent for the Extraction of Glycyrrhizic Acid from Glycyrrhiza glabra: Optimization and Kinetic Evaluation. Ind Eng Chem Res 2021. [DOI: 10.1021/acs.iecr.1c00862] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Kavita J. Lanjekar
- Department of Chemical Engineering, Institute of Chemical Technology, Matunga (E), Mumbai 400019, India
| | - Virendra K. Rathod
- Department of Chemical Engineering, Institute of Chemical Technology, Matunga (E), Mumbai 400019, India
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8
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Fazelian S, Moradi F, Agah S, Hoseini A, Heydari H, Morvaridzadeh M, Omidi A, Pizarro AB, Ghafouri A, Heshmati J. Effect of omega-3 fatty acids supplementation on cardio-metabolic and oxidative stress parameters in patients with chronic kidney disease: a systematic review and meta-analysis. BMC Nephrol 2021; 22:160. [PMID: 33933009 PMCID: PMC8088683 DOI: 10.1186/s12882-021-02351-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 04/12/2021] [Indexed: 11/23/2022] Open
Abstract
Background Omega-3 fatty acids (FAs) have been suggested as a beneficial supplement in chronic kidney disease (CKD) patients, but the results of randomized clinical trials (RCTs) are controversial. We conducted a systematic review and meta-analysis to evaluate all the RCTs about the impact of omega-3 FAs supplementation on cardiometabolic outcomes and oxidative stress parameters in patients with CKD. Methods We performed a systematic database search in PubMed/MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Central, up to May 2020. We included all placebo-controlled randomized trials that assessed the effect of omega-3 FAs supplementation on any cardiometabolic outcomes: blood pressure, total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) or triglycerides (TG) and oxidative stress parameters. Data were pooled using DerSimonian–Laird’s random-effects model. Results Finally, thirteen articles met the inclusion criteria for this review omega-3 FAs supplementation significantly decrease TC (SMD: -0.26; 95% CI: − 0.51, − 0.02; I2 = 52.7%), TG (SMD: -0.22; 95% CI: − 0.43, − 0.02; I2 = 36.0%) and Malondialdehyde (MDA) levels (SMD: -0.91; 95% CI: − 1.29, − 0.54; I2 = 00.0%) and also significantly increase superoxide dismutase (SOD) (SMD: 0.58; 95% CI: 0.27, 0.90; I2 = 00.0%) and Glutathione peroxidase (GPx) (SMD: 0.50; 95% CI: 0.14, 0.86; I2 = 00.0%) activities. However our results show that omega-3 FAs supplementation have no significant effects on HDL, LDL and blood pressure. Conclusion This systematic review and meta-analysis supports current evidence for the clinical benefit of omega-3 FAs intake to improve cardiometabolic parameters in CKD patients. However, well-designed RCTs still needed to provide a conclusive picture in this field. Supplementary Information The online version contains supplementary material available at 10.1186/s12882-021-02351-9.
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Affiliation(s)
- Siavash Fazelian
- Clinical Research Development Unit, Ayatollah Kashani Hospital, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Fatemeh Moradi
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Shahram Agah
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Akramsadat Hoseini
- Department of Education and Health Promotion,School of Health, Iran University of Medical Sciences, Tehran, Iran
| | - Hafez Heydari
- Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Mojgan Morvaridzadeh
- Department of Nutritional Science, School of Nutritional Science and Food Technology, Kermanshah University of Medical Sciences, Farabi Hospital, Faculty of Nutrition Sciences and Food Technology, Postal Code: 6715847141, Isar Square, Kermanshah, Iran
| | - Amirhosein Omidi
- Department of Nutritional Science, School of Nutritional Science and Food Technology, Kermanshah University of Medical Sciences, Farabi Hospital, Faculty of Nutrition Sciences and Food Technology, Postal Code: 6715847141, Isar Square, Kermanshah, Iran
| | | | - Atie Ghafouri
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.
| | - Javad Heshmati
- Department of Nutritional Science, School of Nutritional Science and Food Technology, Kermanshah University of Medical Sciences, Farabi Hospital, Faculty of Nutrition Sciences and Food Technology, Postal Code: 6715847141, Isar Square, Kermanshah, Iran.
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Valenzuela R, Ortiz M, Hernández-Rodas MC, Echeverría F, Videla LA. Targeting n-3 Polyunsaturated Fatty Acids in Non-Alcoholic Fatty Liver Disease. Curr Med Chem 2020; 27:5250-5272. [PMID: 30968772 DOI: 10.2174/0929867326666190410121716] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 12/14/2018] [Accepted: 01/12/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by abnormal hepatic accumulation of triacylglycerides in the absence of alcohol consumption, in association with Oxidative Stress (OS), a pro-inflammatory state and Insulin Resistance (IR), which are attenuated by n-3 long-chain polyunsaturated Fatty Acids (FAs) C20-C22 (LCPUFAs) supplementation. Main causes of NAFLD comprise high caloric intake and a sedentary lifestyle, with high intakes of saturated FAs. METHODS The review includes several searches considering the effects of n-3 LCPUFAs in NAFLD in vivo and in vitro models, using the PubMed database from the National Library of Medicine- National Institutes of Health. RESULT The LCPUFAs eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n- 3, DHA) have a positive effect in diminishing liver steatosis, OS, and the levels of aspartate aminotransferase, alanine aminotransferase and pro-inflammatory cytokines, with improvement of insulin sensitivity and adiponectin levels. The molecular pathways described for n-3 LCPUFAs in cellular and animal models and humans include peroxisome proliferator-activated receptor-α activation favouring FA oxidation, diminution of lipogenesis due to sterol responsive element binding protein-1c downregulation and inflammation resolution. Besides, nuclear factor erythroid-2-related factor-2 activation is elicited by n-3 LCPUFA-derived oxidation products producing direct and indirect antioxidant responses, with concomitant anti-fibrogenic action. CONCLUSION The discussed effects of n-3 LCPUFA supplementation support its use in NAFLD, although having a limited value in NASH, a contention that may involve n-3 LCPUFA oxygenated derivatives. Clinical trials establishing optimal dosages, intervention times, type of patients and possible synergies with other natural products are needed in future studies.
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Affiliation(s)
- Rodrigo Valenzuela
- Department of Nutrition, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile
| | - Macarena Ortiz
- Nutrition and Dietetics School, Faculty of Health Sciences, Catholic University of Maule, Merced 333, Curicó 3340000, Chile
| | - María Catalina Hernández-Rodas
- Department of Nutrition, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile
| | - Francisca Echeverría
- Department of Nutrition, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile
| | - Luis Alberto Videla
- Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile
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10
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El-Beshbishi SN, Saleh NE, Abd el-mageed SA, El-nemr HEDE, Abdalla HA, Shebl AM, Taman A. Effect of omega-3 fatty acids administered as monotherapy or combined with artemether on experimental Schistosoma mansoni infection. Acta Trop 2019; 194:62-68. [PMID: 30910394 DOI: 10.1016/j.actatropica.2019.02.027] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Revised: 01/26/2019] [Accepted: 02/27/2019] [Indexed: 12/11/2022]
Abstract
Schistosomiasis is on the top list of endemic diseases in sub-Saharan Africa. Praziquantel is the drug of choice for treatment of human schistosomiasis. Yet, the sole dependence on the drug raises concerns about the potential for increased drug resistance, which would subsequently result in searching for alternative preventive chemotherapy options, ideally among natural compounds. Therefore, we conducted this work to assess the effect of omega-3 polyunsaturated fatty acids [(ω-3) PUFAs] monotherapy or combined therapy with artemether (ART) against Schistosoma mansoni infection in a mouse model. A total of 42 mice were divided into 4 groups and infected with 50 ± 5 S. mansoni cercariae for 10 weeks. Mice were treated orally with either (ω-3) PUFAs as 273 mg/ kg, 4 times/ week throughout the experiment, ART as a single dose of 400 mg/ kg, 3 weeks post-infection, or combined ART + (ω-3) PUFAs using the same respective treatment regimen, while infected untreated mice were served as controls. The study explored that combined administration of (ω-3) PUFAs and ART has the best schistosomicidal efficacy as it significantly reduced liver and spleen indices, worm count, egg burdens, and granulomas count as well as diameter. Besides, the combined regimen was associated with a significant decrease in both hepatic nitric oxide and serum interleukin-4 level. The results highlighted the possibility of using (ω-3) PUFA combined with ART as a novel anti-schistosomal combination therapy. However, further researches should be conducted to clarify the possible synergistic mechanism/s between the two natural compounds.
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Karimani A, Heidarpour M, Moghaddam Jafari A. Protective effects of glycyrrhizin on sub-chronic diazinon-induced biochemical, hematological alterations and oxidative stress indices in male Wistar rats. Drug Chem Toxicol 2018; 42:300-308. [PMID: 30203683 DOI: 10.1080/01480545.2018.1497053] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
The aim of this study was to elucidate the protective effect of glycyrrhizin on diazinon-induced changes in body and organ weights, blood hematology, lipid profile, biochemistry parameters and tissue markers of oxidative stress in male Wistar rats over a 7-week period. Rats were orally given sublethal dose of diazinon (10 mg/kg daily; 0.008 LD50), while glycyrrhizin (25 mg kg-1 daily) was given alone or in combination with diazinon. At the end of 7th week, statistically significant decrease of pseudocholinesterase activity was detected when diazinon- and glycyrrhizin + diazinon-treated groups were compared to the control group. Diazinon treated rats showed weight loss and organ weight changes which were comparable to other groups. There was a statistically significance in hematological indices except mean corpuscular hemoglobin (MCH) when diazinon treated group was compared to glycyrrhizin + diazinon treated rats. Glycyrrhizin protected the liver and kidney from diazinon toxic effects with significantly decrease in serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase activities as well as ameliorated hepatic and renal function indices (such as bilirubin, total protein, albumin, BUN, creatinine glucose). In addition, glycyrrhizin minimized the hazardous effect of diazinon on plasma lipids and lipoproteins. The protective effects of glycyrrhizin were confirmed by tissue markers of oxidative stress analysis as glycyrrhizin in combination diminished malondialdehyde and glycyrrhizin alone or in combination enhanced thiol group and the ferric reducing power. In accordance to these results, our observations demonstrated the beneficial effects of glycyrrhizin in reducing the toxicity of diazinon.
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Affiliation(s)
- Asieh Karimani
- a Department of Toxicology, School of Veterinary Medicine , Ferdowsi University of Mashhad , Mashhad , Iran.,b Department of Pharmacodynamics and Toxicology, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran
| | - Mohammad Heidarpour
- c Department of Clinical Sciences, School of Veterinary Medicine , Ferdowsi University of Mashhad , Mashhad , Iran
| | - Amir Moghaddam Jafari
- a Department of Toxicology, School of Veterinary Medicine , Ferdowsi University of Mashhad , Mashhad , Iran
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Eissa LA, Kenawy HI, El-Karef A, Elsherbiny NM, El-Mihi KA. Antioxidant and anti-inflammatory activities of berberine attenuate hepatic fibrosis induced by thioacetamide injection in rats. Chem Biol Interact 2018; 294:91-100. [PMID: 30138605 DOI: 10.1016/j.cbi.2018.08.016] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Revised: 07/26/2018] [Accepted: 08/17/2018] [Indexed: 12/14/2022]
Abstract
Berberine (BBR) is an isoquinoline alkaloid extracted from the roots, rhizomes and stems of coptis. Liver fibrosis is a worldwide health problem with no established therapy until now. The aim of our study is to investigate the efficacy of BBR on hepatic fibrosis induced in rats and to uncover other mechanisms. Rats were injected with thioacetamide (TAA) (200 mg/kg, i.p) twice per week for 6 weeks to induce fibrosis. Treated groups were gavaged with BBR (50 mg/kg/day, p.o) simultaneously with TAA injection. Hepatic antioxidant enzymes (catalase, SOD, GPx) were assessed in hepatic homogenate. Their activities were attenuated by TAA injection and elevated by BBR administration. Additionally, serum IL-6 and mRNA levels of IL-1β, IL-6, IL-10 and IFN-γ were evaluated as inflammatory markers. Our results showed that BBR suppressed the inflammation induced by TAA injection. Tissue expression of α-SMA (marker of activated HSCs), TGF-β1 and fibronectin were measured by immunohistochemistry as well as mRNA expressions of TGF-β1 and fibronectin were quantified as fibrotic markers. The collagen deposition in hepatic tissues was assessed by Masson's trichome staining. BBR significantly alleviated TGF-β1 production, decreased collagen and fibronectin deposition and consequently attenuated hepatic fibrogenesis. Akt pathway controls cell survival, proliferation, migration and adhesion. The relative phosphorylation of Akt was determined in hepatic homogenates that was increased with TAA injection and decreased by BBR treatment. Inhibition of Akt pathway has been linked to the intrinsic pathway of apoptosis. Caspase-3, caspase-9, Bcl-2 and Bax were quantified as apoptotic markers using qPCR and also caspase-3 by immunohistochemistry. BBR-treated rats showed an increase in the expression of apoptotic markers. Moreover, BBR-treated rats showed restoration of normal liver lobular architecture as shown by H&E staining. In conclusion, BBR is a potential therapeutic candidate for liver fibrosis owing to its antioxidant and anti-inflammatory activities.
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Affiliation(s)
- Laila Ahmed Eissa
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
| | - Hany Ibrahim Kenawy
- Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt
| | - Amro El-Karef
- Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt
| | - Nehal Mohsen Elsherbiny
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia
| | - Kholoud Alaa El-Mihi
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
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Eraky SM, El-Mesery M, El-Karef A, Eissa LA, El-Gayar AM. Silymarin and caffeine combination ameliorates experimentally-induced hepatic fibrosis through down-regulation of LPAR1 expression. Biomed Pharmacother 2018; 101:49-57. [PMID: 29477472 DOI: 10.1016/j.biopha.2018.02.064] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Revised: 02/14/2018] [Accepted: 02/15/2018] [Indexed: 01/08/2023] Open
Abstract
AIMS Lysophosphatidic acid is a lipid mediator that is supposed to be implicated in hepatic fibrosis. Silymarin and caffeine are natural compounds known for their anti-inflammatory and antioxidant effects. Our study aimed to explore the effect of silymarin, caffeine, and their combination on lysophosphatidic acid receptor 1 (LPAR1) pathway in thioacetamide (TAA)-induced hepatic fibrosis. MAIN METHODS Hepatic fibrosis was induced in male Sprague-Dawley rats by intraperitoneal injection of 200 mg/kg of TAA twice a week for 8 weeks. Silymarin (50 mg/kg), caffeine (50 mg/kg), and their combination (50 mg/kg silymarin + 50 mg/kg caffeine) were orally given to rats every day for 8 weeks along with TAA injection. Liver functions were measured. Histopathological examination of liver tissues was performed using hematoxylin and eosin and Masson's trichrome staining. mRNA expressions of LPAR1, transforming growth factor beta 1 (TGF-β1), connective tissue growth factor (CTGF), and alpha smooth muscle actin (α-SMA) were measured using RT-PCR. LPAR1 tissue expression was scored using immunohistochemistry. KEY FINDINGS Silymarin, caffeine, and their combination significantly improved liver function. They caused significant decrease in fibrosis and necro-inflammatory scores. Combination of silymain and caffeine caused a significant decrease in the necro-inflammatory score than the single treatment with silymarin or caffeine. In addition, silymarin, caffeine, and their combination significantly decreased hepatic LPAR1, TGF-β1, CTGF, and α-SMA gene expressions and LPAR1 tissue expression. SIGNIFICANCE Silymarin, caffeine, and their combination protect against liver fibrosis through down-regulation of LPAR1, TGF-β1, and CTGF.
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Affiliation(s)
- Salma M Eraky
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
| | - Mohamed El-Mesery
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Amro El-Karef
- Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Laila A Eissa
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
| | - Amal M El-Gayar
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
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14
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Evaluation of the hepatoprotective effect of combination between hinokiflavone and Glycyrrhizin against CCl 4 induced toxicity in rats. Saudi Pharm J 2018; 26:496-503. [PMID: 29844720 PMCID: PMC5962645 DOI: 10.1016/j.jsps.2018.02.009] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Accepted: 02/05/2018] [Indexed: 01/04/2023] Open
Abstract
Liver diseases are one of the fatal syndromes due to the vital role of the liver. Most of the effective treatment of liver conditions are of natural origin. Silymarin (SI) is the standard drug used for treatment of impaired liver functions. Two natural compounds possessing promising liver protection and with different chemical structures namely; the bioflavonoid hinokiflavone (HF) isolated from Junipers phoenicea family Cupressaceae and the sweet saponin Glycyrrhizin (GL) present in Glycyrrhiza glabra (liquorice) were selected for the current study. Since the two compounds are of different nature, they may act by different mechanisms and express synergistic effect. Combination of the two compounds using to dose levels were challenged with single doses of HF, GL and SI as well. The comparison was monitored via measuring serum biochemical parameters including, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltranspeptidase (GGT), alkaline phosphatase (ALP) and total bilirubin, tissue parameters such as MDA, NP-SH and TP, histopathological study using light and electron microscope. Protective effect on kidney was also monitored histopathologically and biochemically through observing the levels of LDH, creatinine, creatinine-kinase, urea and uric acid. The combinations of HF and GL showed protective effect more than the used single doses of HF and GL alone. However, SI was superior to the used combination in the two used doses in all the measured parameters. The liver and kidney cells appearance under normal and electron microscope showed that SI treated groups showed almost normal cells with slight toxic signs. Cells from group treated with the higher doses of the combination of HF and GL showed slight signs of intoxication under light and electron microscope indicating good level of protection. Although the combination of HF and GL expressed good protection in the higher dose, however, the combination did not exceed the protective effect of SI.
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Abo El-Magd NF, El-Mesery M, El-Karef A, El-Shishtawy MM. Glycyrrhizin ameliorates high fat diet-induced obesity in rats by activating NrF2 pathway. Life Sci 2018; 193:159-170. [PMID: 29129772 DOI: 10.1016/j.lfs.2017.11.005] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2017] [Revised: 11/04/2017] [Accepted: 11/06/2017] [Indexed: 12/27/2022]
Abstract
AIM Obesity based on insulin resistance is a state of chronic oxidative stress and inflammation that are highly regulated through nuclear factor Erythroid 2-related factor 2 (NrF2) pathway. MATERIALS AND METHODS 70 male Wistar rats were randomized into two models. The prophylactic model was 10weeks and rats were grouped into: normal group, GL group (received glycyrrhizin 50mg/kg/day orally along with normal pellet diet), HFD group and HFD+ GL group (received glycyrrhizin along with HFD). The treatment model was 14weeks and rats were grouped into: normal group, HFD group and HFD+GL group (received glycyrrhizin from the week 10). KEY FINDINGS Glycyrrhizin decreased significantly rat weights and insulin resistance, normalized lipid profile and reduced significantly the adipocytes size in adipose tissue and lipid deposition in the liver tissue through histopathologic examination. Furthermore, glycyrrhizin ameliorated obesity-induced oxidative stress which indicated by significant decrease in liver malondialdehyde level (P<0.001) and increase in the total antioxidant capacity (P<0.001). Interestingly, molecular mechanism of glycyrrhizin was explored, that included significant reduction of liver gluconeogenic enzymes mRNA expression (P<0.001), a significant increase of liver insulin receptor, NrF2 and homooxygenase-1 mRNA expressions (P<0.001) and significant increase and nuclear translocation of NrF2 in liver tissue. SIGNIFICANCE Glycyrrhizin ameliorates HFD-induced obesity in rats that may be attributed to its ability to increase insulin receptor expression and to activate NrF2 and subsequent homooxygenase-1 pathway. Thus, this work represents a safe natural compound (glycyrrhizin) that has a great role either as prophylaxis or treatment for insulin resistance related to obesity.
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Affiliation(s)
- Nada F Abo El-Magd
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Mohamed El-Mesery
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Amro El-Karef
- Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Mamdouh M El-Shishtawy
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
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El-Mihi KA, Kenawy HI, El-Karef A, Elsherbiny NM, Eissa LA. Naringin attenuates thioacetamide-induced liver fibrosis in rats through modulation of the PI3K/Akt pathway. Life Sci 2017; 187:50-57. [PMID: 28830755 DOI: 10.1016/j.lfs.2017.08.019] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2017] [Revised: 08/10/2017] [Accepted: 08/18/2017] [Indexed: 12/12/2022]
Abstract
AIMS Naringin (NR) is a flavanone glycoside extracted from grapefruits and citrus fruits. The aim of this study is to investigate the antifibrotic efficacy of NR in thioacetamide (TAA)-induced hepatic fibrosis in rats through evaluating NR effect on the PI3K/Akt pathway. MAIN METHODS Hepatic fibrosis was induced in rats by intraperitoneal injection of TAA (200mg/kg) twice per week for 6weeks. Simultaneously, NR (40mg/kg/day, p.o.) was given along with TAA injection. The ratio of P-Akt/Akt was assessed in hepatic homogenate as well as antioxidant enzymes (catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx)) and lipid peroxidation marker, malondialdehyde (MDA). Serum level of interleukin (IL)-6 were measured using ELISA. Hepatic tissues were examined histopathologically using hematoxylin and eosin (H&E) and Masson trichome staining. Tissue expression of alpha smooth muscle actin (α-SMA), transforming growth factor β1 (TGF-β1), caspase-3 and fibronectin were scored immunohistochemically. Finally, the mRNA level of cytokine genes (IL-1β, IL-6, IL-10, interferon gamma (IFN-γ)), caspase-3, TGF-β1 and fibronectin were quantified using qPCR. KEY FINDINGS NR significantly suppressed Akt phosphorylation associated with increased number of caspase-3 positive cells especially in the fibrotic areas. Liver tissues of treated rats showed restoration of normal liver histology and decrease in collagen and fibronectin deposition. Furthermore, NR treatment ameliorated oxidative stress and inflammatory cytokine production. SIGNIFICANCE NR alleviated experimental liver fibrosis through inhibition of PI3K/Akt pathway beside its anti-inflammatory and antioxidant effects. Therefore, NR is a promising therapeutic candidate for hepatic fibrosis.
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Affiliation(s)
- Kholoud Alaa El-Mihi
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
| | - Hany Ibrahim Kenawy
- Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Amro El-Karef
- Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | | | - Laila Ahmed Eissa
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
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17
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Rani R, Dahiya S, Dhingra D, Dilbaghi N, Kim KH, Kumar S. Evaluation of anti-diabetic activity of glycyrrhizin-loaded nanoparticles in nicotinamide-streptozotocin-induced diabetic rats. Eur J Pharm Sci 2017; 106:220-230. [DOI: 10.1016/j.ejps.2017.05.068] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Revised: 04/23/2017] [Accepted: 05/31/2017] [Indexed: 12/21/2022]
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18
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Elmansi A, El-Karef A, Shishtawy M, Eissa L. Hepatoprotective Effect of Curcumin on Hepatocellular Carcinoma Through Autophagic and Apoptic Pathways. Ann Hepatol 2017; 16:607-618. [PMID: 28611265 DOI: 10.5604/01.3001.0010.0307] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND RATIONALE Microtubule-associated protein light chain 3-II (LC3-II), and Sequestosome-1 (SQSTM1) are proteins that can be used as markers for autophagic pathway. Bcl-2 protein is reported to be inversely correlated with apoptosis. We aimed to investigate the effects of curcumin on liver inflammation and fibrosis up to the first dysplastic stage of Hepatocellular carcinoma (HCC) induced by Thioacetamide (TAA) in rats and to clarify the effects of curcumin on LC3-II, SQSTM1, and Bcl-2. Male Sprague-Dawley rats were randomized into four groups: Control group, TAA group, Curcumin low-dose group, and Curcumin highdose group. The last three groups received TAA 200 mg/kg i.p. twice weekly for 18 weeks. Oxidative stress markers as hepatic malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity were measured by colorimetric methods. Hepatic SQSTM1 concentration was measured by ELISA, and gene expression levels of Bcl-2, and LC3-II were measured by RT-PCR.We also investigated the in vitro effect of curcumin on HepG2 cells viability through MTT assay, and the involvement of autophagy in this effect. RESULTS Curcumin increased the survival percent in rats, decreased -fetoprotein (AFP) concentration, and serum aspartate aminotransferase (AST) activity, and increased serum albumin concentration. Curcumin also significantly reduced oxidative stress in liver, inhibited apoptosis, and induced autophagy. In vitro, curcumin (50 µM) decreased HepG2 cells viabilityand the concentration of SQSTM1. CONCLUSIONS Curcumin leads to protection against TAA induced HCC up to the first dysplastic stage through activating autophagic pathway and inhibiting apoptosis. Also, the antioxidant activity of curcumin almost prevents liver fibrosis.
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MESH Headings
- Animals
- Anticarcinogenic Agents/pharmacology
- Antineoplastic Agents, Phytogenic/pharmacology
- Apoptosis/drug effects
- Autophagy/drug effects
- Carcinoma, Hepatocellular/chemically induced
- Carcinoma, Hepatocellular/metabolism
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/prevention & control
- Cell Survival/drug effects
- Cell Transformation, Neoplastic/chemically induced
- Cell Transformation, Neoplastic/drug effects
- Cell Transformation, Neoplastic/metabolism
- Cell Transformation, Neoplastic/pathology
- Curcumin/pharmacology
- Dose-Response Relationship, Drug
- Hep G2 Cells
- Humans
- Liver/drug effects
- Liver/metabolism
- Liver/pathology
- Liver Neoplasms/chemically induced
- Liver Neoplasms/metabolism
- Liver Neoplasms/pathology
- Liver Neoplasms/prevention & control
- Male
- Microtubule-Associated Proteins/metabolism
- Oxidative Stress/drug effects
- Proto-Oncogene Proteins c-bcl-2/metabolism
- Rats, Sprague-Dawley
- Sequestosome-1 Protein/metabolism
- Signal Transduction/drug effects
- Thioacetamide
- Time Factors
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Affiliation(s)
- Ahmed Elmansi
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
| | - Amro El-Karef
- Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Mamdouh Shishtawy
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
| | - Laila Eissa
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
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Basheer AS, Siddiqui A, Paudel YN, Hassan MQ, Imran M, Najmi AK, Akhtar M. Hepatoprotective and antioxidant effects of fish oil on isoniazid-rifampin induced hepatotoxicity in rats. PHARMANUTRITION 2017. [DOI: 10.1016/j.phanu.2017.01.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Samra YA, Said HS, Elsherbiny NM, Liou GI, El-Shishtawy MM, Eissa LA. Cepharanthine and Piperine ameliorate diabetic nephropathy in rats: role of NF-κB and NLRP3 inflammasome. Life Sci 2016; 157:187-199. [PMID: 27266851 DOI: 10.1016/j.lfs.2016.06.002] [Citation(s) in RCA: 99] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Revised: 05/31/2016] [Accepted: 06/02/2016] [Indexed: 01/09/2023]
Abstract
AIMS Hyperglycemia leads to elevation of oxidative stress and proinflammatory cytokines which are the main causes of diabetic nephropathy (DN). NLRP3 inflammasome and thioredoxin-interacting protein (TXNIP) are recently assumed to participate in the development of DN. We aimed to investigate the effects of Cepharanthine (CEP), Piperine (Pip) and their combination in streptozotocin (STZ)-induced DN focusing on their role to modulate NLRP3 and TXNIP induced inflammation. MAIN METHODS Diabetic rats were treated with intraperitoneal (i.p.) injection of CEP (10mg/kg/day), Pip (30mg/kg/day) or their combination for 8weeks. Nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) were assessed by ELISA technique. TXNIP and NLRP3 genes expressions were evaluated by real time-PCR. KEY FINDINGS Diabetic rats showed significant increase in renal TXNIP and NLRP3 expression. CEP, Pip or their combination significantly decreased TXNIP and NLRP3 expression in diabetic kidneys. Hyperglycemia induced NF-κB activation leading to increased IL-1β and TNF-α levels. CEP, Pip or their combination showed significant inhibition of NF-κB together with decreased IL-1β and TNF-α levels in diabetic rats. Also, diabetic rats showed significant decrease in creatinine clearance and increase in blood glucose, serum creatinine, blood urea nitrogen, malondialdehyde, proteinuria, and kidney weight to body Weight ratio. All of these changes were reversed by CEP, Pip or their combination. SIGNIFICANCE The antioxidant and anti-inflammatory effects of CEP and Pip which were accompanied by inhibition of NF-κB and NLRP3 activation might be helpful mechanisms to halt the progression of DN.
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Affiliation(s)
- Yara A Samra
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
| | - Heba S Said
- Department of Microbiology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Nehal M Elsherbiny
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Gregory I Liou
- Department of Ophthalmology, Augusta University, Augusta, GA 30912, USA
| | - Mamdouh M El-Shishtawy
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Laila A Eissa
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
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Oda SS. The influence of Omega3 fatty acids supplementation against aluminum-induced toxicity in male albino rats. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2016; 23:14354-14361. [PMID: 27055897 DOI: 10.1007/s11356-016-6578-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/26/2015] [Accepted: 03/27/2016] [Indexed: 06/05/2023]
Abstract
This study evaluated the protective and antioxidant potential of Omega3 fatty acids (FAs) against aluminum intoxicated male albino rats. Twenty-four male albino rats were divided into four equal groups: group I served as control; group II (Omega3-treated) received Omega3 FAs 1000 mg/kg bwt/day orally; group III (aluminum-treated) received aluminum chloride 100 mg/kg bwt/day orally and group IV (aluminum + Omega3-treated) received aluminum chloride 100 mg/kg bwt/day and Omega3 FAs 1000 mg/kg bwt/day orally. Treatments lasted for 4 weeks. Results indicate that administration of aluminum chloride showed non-significant changes in serum alanine aminotransferase, urea, and creatinine levels, a significant increase in serum aspartate aminotransferase and malondialdehyde as well as a significant reduction in serum-reduced glutathione levels. Aluminum treatment induced histopathological alterations in the liver, kidney, brain, testes, and epididymis. Omega3 FAs supplementation improved the serum parameters, enhanced endogenous antioxidant status, reduced lipid peroxidation, and ameliorated the intensity of the histopathological lesions. These findings reveal that Omega3 FAs supplementation can lighten the toxic effects of aluminum through their antioxidant and free radical-scavenging effects.
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Affiliation(s)
- Samah S Oda
- Department of Pathology, Faculty of Veterinary Medicine, Alexandria University, P.O. Box. 22758, Edfina-Rashid-Behera, Egypt.
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22
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Abstract
Liquorice foliage
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