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Ashique S, Mishra N, Mantry S, Garg A, Kumar N, Gupta M, Kar SK, Islam A, Mohanto S, Subramaniyan V. Crosstalk between ROS-inflammatory gene expression axis in the progression of lung disorders. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:417-448. [PMID: 39196392 DOI: 10.1007/s00210-024-03392-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Accepted: 08/16/2024] [Indexed: 08/29/2024]
Abstract
A significant number of deaths and disabilities worldwide are brought on by inflammatory lung diseases. Many inflammatory lung disorders, including chronic respiratory emphysema, resistant asthma, resistance to steroids, and coronavirus-infected lung infections, have severe variants for which there are no viable treatments; as a result, new treatment alternatives are needed. Here, we emphasize how oxidative imbalance contributes to the emergence of provocative lung problems that are challenging to treat. Endogenic antioxidant systems are not enough to avert free radical-mediated damage due to the induced overproduction of ROS. Pro-inflammatory mediators are then produced due to intracellular signaling events, which can harm the tissue and worsen the inflammatory response. Overproduction of ROS causes oxidative stress, which causes lung damage and various disease conditions. Invasive microorganisms or hazardous substances that are inhaled repeatedly can cause an excessive amount of ROS to be produced. By starting signal transduction pathways, increased ROS generation during inflammation may cause recurrent DNA damage and apoptosis and activate proto-oncogenes. This review provides information about new targets for conducting research in related domains or target factors to prevent, control, or treat such inflammatory oxidative stress-induced inflammatory lung disorders.
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Affiliation(s)
- Sumel Ashique
- Department of Pharmaceutics, Bengal College of Pharmaceutical Sciences & Research, Durgapur, West Bengal, 713212, India.
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144411, India.
| | - Neeraj Mishra
- Department of Pharmaceutics, Amity Institute of Pharmacy, Amity University Madhya Pradesh (AUMP), Gwalior, MP, 474005, India
| | - Shubhrajit Mantry
- Department of Pharmaceutics, Department of Pharmacy, Sarala Birla University, Ranchi, Jharkhand, 835103, India
| | - Ashish Garg
- Department of Pharmaceutics, Guru Ramdas Khalsa Institute of Science and Technology (Pharmacy), Jabalpur, Madhya Pradesh, 483001, India
| | - Nitish Kumar
- SRM Modinagar College of Pharmacy, SRM Institute of Science and Technology (Deemed to Be University), Delhi-NCR Campus, Modinagar, Ghaziabad, Uttar Pradesh, 201204, India
| | - Madhu Gupta
- Department of Pharmaceutics, Delhi Pharmaceutical Sciences and Research University, Delhi, 110017, India
| | - Sanjeeb Kumar Kar
- Department of Pharmaceutical Chemistry, Department of Pharmacy, Sarala Birla University, Ranchi, Jharkhand, 835103, India
| | - Anas Islam
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, 226026, India
| | - Sourav Mohanto
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to Be University), Mangalore, Karnataka, 575018, India.
| | - Vetriselvan Subramaniyan
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500, Subang Jaya, Selangor, Malaysia.
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Kokoulin MS, Kuzmich AS, Filshtein AP, Prassolov VS, Romanenko LA. Capsular polysaccharide from the marine bacterium Cobetia marina induces apoptosis via both caspase-dependent and mitochondria-mediated pathways in HL-60 cells. Carbohydr Polym 2025; 347:122791. [PMID: 39487004 DOI: 10.1016/j.carbpol.2024.122791] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Revised: 08/18/2024] [Accepted: 09/20/2024] [Indexed: 11/04/2024]
Abstract
In the present study, we investigated the antiproliferative effect of the capsular polysaccharide (CPS) from marine Gram-negative bacterium Cobetia marina (formerly C. pacifica) KMM 3878 against human leukemia cells in vitro and the potential molecular mechanism underlying this activity. Our results showed that the CPS could inhibit the proliferation of HL-60 cells in a dose-dependent manner with no effect on normal PBMC cells. HL-60 cells treated with the CPS exhibited typical morphologic and biochemical signs of apoptosis. We found that the CPS caused the collapse of mitochondrial transmembrane potential (ΔΨm), activated caspases-8,-9, and - 3, decreased the ratio of anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins, increased ROS production and TNF-α secretion, and stimulated phosphorylation of p38 MAPK and p53 in HL-60 cells. Taken together, these data suggest that both extracellular and intracellular signaling pathways contribute to the CPS-induced apoptosis in HL-60 cells.
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Affiliation(s)
- Maxim S Kokoulin
- G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159/2, Prospect 100 let Vladivostoku, Vladivostok 690022, Russian Federation.
| | - Alexandra S Kuzmich
- G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159/2, Prospect 100 let Vladivostoku, Vladivostok 690022, Russian Federation
| | - Alina P Filshtein
- G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159/2, Prospect 100 let Vladivostoku, Vladivostok 690022, Russian Federation
| | - Vladimir S Prassolov
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova, 32, 119991 Moscow, Russian Federation
| | - Lyudmila A Romanenko
- G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159/2, Prospect 100 let Vladivostoku, Vladivostok 690022, Russian Federation
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Al-Suhaimi E, AlQuwaie R, AlSaqabi R, Winarni D, Dewi FRP, AlRubaish AA, Shehzad A, Elaissari A. Hormonal orchestra: mastering mitochondria's role in health and disease. Endocrine 2024; 86:903-929. [PMID: 39172335 DOI: 10.1007/s12020-024-03967-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 07/10/2024] [Indexed: 08/23/2024]
Abstract
Mitochondria is a subcellular organelle involved in the pathogenesis of cellular stress, immune responses, differentiation, metabolic disorders, aging, and death by regulating process of fission, fusion, mitophagy, and transport. However, an increased interest in mitochondria as powerhouse for ATP production, the mechanisms of mitochondria-mediated cellular dysfunction in response to hormonal interaction remains unknown. Mitochondrial matrix contains chaperones and proteases that regulate intrinsic apoptosis pathway through pro-apoptotic Bcl-2 family's proteins Bax/Bak, and Cyt C release, and induces caspase-dependent and independent cells death. Energy and growth regulators such as thyroid hormones have profound effect on mitochondrial inner membrane protein and lipid compositions, ATP production by regulating oxidative phosphorylation system. Mitochondria contain cholesterol side-chain cleavage enzyme, P450scc, ferredoxin, and ferredoxin reductase providing an essential site for steroid hormones biosynthesis. In line with this, neurohormones such as oxytocin, vasopressin, and melatonin are correlated with mitochondrial integrity, displaying therapeutic implications for inflammatory and immune responses. Melatonin's also displayed protective role against oxidative stress and mitochondrial synthesis of ROS, suggesting a defense mechanism against aging-related diseases. An imbalance in mitochondrial bioenergetics can cause neurodegenerative disorders, cardiovascular diseases, and cancers. Hormone-induced PGC-1α stimulates mitochondrial biogenesis via activation of NRF1 and NRF2, which in turn triggers mtTFA in brown adipose and cardiac myocytes. Mitochondria can be transferred through cells merging, exosome-mediated transfer, and tunneling through nanotubes. By delineating the underlying molecular mechanism of hormonal mitochondrial interaction, this study reviews the dynamics mechanisms of mitochondria and its effects on cellular level, health, diseases, and therapeutic strategies targeting mitochondrial diseases.
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Affiliation(s)
- Ebtesam Al-Suhaimi
- Vice presidency for Scientific Research and Innovation, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
- King Abdulaziz and his Companions Foundation for Giftedness and Creativity "Mawhiba", Riyadh, Saudi Arabia.
| | - Rahaf AlQuwaie
- Master Program of Biotechnology, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Reem AlSaqabi
- Master Program of Biotechnology, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Dwi Winarni
- Department of Biology, Faculty of Science and Technology, Universitas Airlangga, Surabaya, East Java, Indonesia
| | - Firli Rahmah Primula Dewi
- Department of Biology, Faculty of Science and Technology, Universitas Airlangga, Surabaya, East Java, Indonesia
| | - Abdullah A AlRubaish
- College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Adeeb Shehzad
- Biodiversity Unit, Research Center, Dhofar University, Salalah, Oman
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Wood JPM, Chidlow G, Wall GM, Casson RJ. N-acetylcysteine amide and di- N-acetylcysteine amide protect retinal cells in culture via an antioxidant action. Exp Eye Res 2024; 248:110074. [PMID: 39251120 DOI: 10.1016/j.exer.2024.110074] [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: 04/17/2024] [Revised: 09/03/2024] [Accepted: 09/04/2024] [Indexed: 09/11/2024]
Abstract
Reactive oxygen species (ROS) play a significant role in toxicity to the retina in a variety of diseases. N-acetylcysteine (NAC), N-acetylcysteine amide (NACA) and the dimeric di-N-acetylcysteine amide (diNACA) were evaluated in terms of protecting retinal cells, in vitro, in a variety of stress models. Three types of rat retinal cell cultures were utilized in the study: macroglial-only cell cultures, neuron-only retinal ganglion cell (RGC) cultures, and mixed cultures containing retinal glia and neurons. Ability of test agents to attenuate oxidative stress in all cultures was ascertained. In addition, capability of agents to protect against a variety of alternate clinically-relevant stressors, including excitotoxins and mitochondrial electron transport chain inhibitors, was also evaluated. Capacity of test agents to elevate cellular levels of reduced glutathione under normal and compromised conditions was also determined. NAC, NACA and diNACA demonstrated concentration-dependent cytoprotection against oxidative stress in all cultures. These three compounds, however, had differing effects against a variety of alternate insults to retinal cells. The most protective agent was NACA, which was most potent against the most stressors (including oxidative stress, mitochondrial impairment by antimycin A and azide, and glutamate-induced excitotoxicity). Similar to NAC, NACA increased glutathione levels in non-injured cells, although diNACA did not, suggesting a different, unknown mechanism of antioxidant activity for the latter. In support of this, diNACA was the only agent to attenuate rotenone-induced toxicity in mitochondria. NAC, NACA and diNACA exhibited varying degrees of antioxidant activity, i.e., protected cultured rat retinal cells from a variety of stressors which were designed to mimic aspects of the pathology of different retinal diseases. A general rank order of activity was observed: NACA ≥ diNACA > NAC. These results warrant further exploration of NACA and diNACA as antioxidant therapeutics for the treatment of retinal diseases, particularly those involving oxidative stress. Furthermore, we have defined the battery of tests carried out as the "Wood, Chidlow, Wall and Casson (WCWC) Retinal Antioxidant Indices"; we believe that these are of great value for screening molecules for potential to reduce retinal oxidative stress in a range of retinal diseases.
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Affiliation(s)
- John P M Wood
- Discipline of Ophthalmology & Visual Sciences, Level 7 Adelaide Health and Medical Sciences Building, University of Adelaide, North Terrace, Adelaide, SA, 5000, Australia; South Australian Institute of Ophthalmology, Royal Adelaide Hospital, Port Road, SA 5000, Australia.
| | - Glyn Chidlow
- Discipline of Ophthalmology & Visual Sciences, Level 7 Adelaide Health and Medical Sciences Building, University of Adelaide, North Terrace, Adelaide, SA, 5000, Australia; South Australian Institute of Ophthalmology, Royal Adelaide Hospital, Port Road, SA 5000, Australia
| | | | - Robert J Casson
- Discipline of Ophthalmology & Visual Sciences, Level 7 Adelaide Health and Medical Sciences Building, University of Adelaide, North Terrace, Adelaide, SA, 5000, Australia; South Australian Institute of Ophthalmology, Royal Adelaide Hospital, Port Road, SA 5000, Australia
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Jiang C, Shen C, Ni M, Huang L, Hu H, Dai Q, Zhao H, Zhu Z. Molecular mechanisms of cisplatin resistance in ovarian cancer. Genes Dis 2024; 11:101063. [PMID: 39224110 PMCID: PMC11367050 DOI: 10.1016/j.gendis.2023.06.032] [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: 01/30/2023] [Revised: 06/06/2023] [Accepted: 06/27/2023] [Indexed: 09/04/2024] Open
Abstract
Ovarian cancer is one of the most common malignant tumors of the female reproductive system. The majority of patients with advanced ovarian cancer are mainly treated with cisplatin-based chemotherapy. As the most widely used first-line anti-neoplastic drug, cisplatin produces therapeutic effects through multiple mechanisms. However, during clinical treatment, cisplatin resistance has gradually emerged, representing a challenge for patient outcome improvement. The mechanism of cisplatin resistance, while known to be complex and involve many processes, remains unclear. We hope to provide a new direction for pre-clinical and clinical studies through this review on the mechanism of ovarian cancer cisplatin resistance and methods to overcome drug resistance.
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Affiliation(s)
- Chenying Jiang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, China
| | - Chenjun Shen
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, China
| | - Maowei Ni
- The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang 310005, China
| | - Lili Huang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, China
| | - Hongtao Hu
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, China
| | - Qinhui Dai
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, China
| | - Huajun Zhao
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, China
| | - Zhihui Zhu
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, China
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Baykara S, Kazğan A, Yıldırım H, Tabara MF, Kaşıkcı HÖ, Danacı Keleş D. Retinal changes in generalized anxiety disorder patients. Int J Psychiatry Med 2024; 59:270-286. [PMID: 37870071 DOI: 10.1177/00912174231209771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2023]
Abstract
OBJECTIVE Optical coherence tomography (OCT) is a method that allows high-resolution cross-sectional imaging of biological tissues. It was suggested that changes in the cranial structure or functions would be reflected in the retina. OCT has been an important method in the diagnosis and follow-up of diseases via morphometric or quantitative retinal measurements. Free radicals, inflammatory processes, and neurotransmission disorders play a role in the etiology of generalized anxiety disorder (GAD). The study aimed to demonstrate the retinal changes in GAD patients due to neurodegeneration based on the comparison of the OCT data of the GAD patients and controls, and the differences between OCT findings of GAD patients and those of controls. METHODS The study group included 21 GAD patients. The control group included 21 individuals without any known psychiatric or organic disease, including eye diseases. RESULTS There was a statistically significant difference between the macular volumes (MV) of the GAD and control groups, the macular volume was lower in the GAD group. There were positive correlations between BDI scores and MV, GCLT, RNFLT-i, RNFLT-n, between BAE scores and (RNFLT-n), and between the CGI severity scale scores and MV, RNFLT-n, and RNFLT-t. CONCLUSION OCT analysis of the GAD patients demonstrated that MV values were lower when compared to the control group. Patients with GAD should be screened for these retinal changes. OCT, a simple, non-invasive, and relatively inexpensive method could be employed as a supplementary method in the follow-up of GAD patients.
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Affiliation(s)
- Sema Baykara
- Department of Psychiatry, Erenkoy Psychiatry and Neurology Training and Research Hospital, Istanbul, Turkey
| | - Aslı Kazğan
- Faculty of Medicine, Department of Psychiatry, Fırat University, Elazig, Turkey
| | - Hakan Yıldırım
- Faculty of Medicine, Department of Ophthalmology, Fırat University, Elazig, Turkey
| | | | - Halim Ömer Kaşıkcı
- Department of Family Medicine, Erenkoy Psychiatry and Neurology Training and Research Hospital, Istanbul, Turkey
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Chen C, Cui D, Li J, Ren C, Yang D, Xiang P, Liu J. Organophosphorus Flame Retardant TPP-Induced Human Corneal Epithelial Cell Apoptosis through Caspase-Dependent Mitochondrial Pathway. Int J Mol Sci 2024; 25:4155. [PMID: 38673741 PMCID: PMC11050068 DOI: 10.3390/ijms25084155] [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: 03/05/2024] [Revised: 04/01/2024] [Accepted: 04/04/2024] [Indexed: 04/28/2024] Open
Abstract
A widely used organophosphate flame retardant (OPFR), triphenyl phosphate (TPP), is frequently detected in various environmental media and humans. However, there is little known on the human corneal epithelium of health risk when exposed to TPP. In this study, human normal corneal epithelial cells (HCECs) were used to investigate the cell viability, morphology, apoptosis, and mitochondrial membrane potential after they were exposed to TPP, as well as their underlying molecular mechanisms. We found that TPP decreased cell viability in a concentration-dependent manner, with a half maximal inhibitory concentration (IC50) of 220 μM. Furthermore, TPP significantly induced HCEC apoptosis, decreased mitochondrial membrane potential in a dose-dependent manner, and changed the mRNA levels of the apoptosis biomarker genes (Cyt c, Caspase-9, Caspase-3, Bcl-2, and Bax). The results showed that TPP induced cytotoxicity in HCECs, eventually leading to apoptosis and changes in mitochondrial membrane potential. In addition, the caspase-dependent mitochondrial pathways may be involved in TPP-induced HCEC apoptosis. This study provides a reference for the human corneal toxicity of TPP, indicating that the risks of OPFR to human health cannot be ignored.
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Affiliation(s)
| | | | | | | | | | - Ping Xiang
- Yunnan Province Innovative Research Team of Environmental Pollution, Food Safety and Human Health, Institute of Environmental Remediation and Human Health, School of Ecology and Environment, Southwest Forestry University, Kunming 650224, China; (C.C.); (D.C.); (J.L.); (C.R.); (D.Y.)
| | - Jianxiang Liu
- Yunnan Province Innovative Research Team of Environmental Pollution, Food Safety and Human Health, Institute of Environmental Remediation and Human Health, School of Ecology and Environment, Southwest Forestry University, Kunming 650224, China; (C.C.); (D.C.); (J.L.); (C.R.); (D.Y.)
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Cao Y, Zhou X, Nie Q, Zhang J. Inhibition of the thioredoxin system for radiosensitization therapy of cancer. Eur J Med Chem 2024; 268:116218. [PMID: 38387331 DOI: 10.1016/j.ejmech.2024.116218] [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: 11/20/2023] [Revised: 01/28/2024] [Accepted: 02/04/2024] [Indexed: 02/24/2024]
Abstract
Radiotherapy (RT) stands as a cornerstone in the clinical armamentarium against various cancers due to its proven efficacy. However, the intrinsic radiation resistance exhibited by cancer cells, coupled with the adverse effects of RT on normal tissues, often compromises its therapeutic potential and leads to unwanted side effects. This comprehensive review aims to consolidate our understanding of how radiosensitizers inhibit the thioredoxin (Trx) system in cellular contexts. Notable radiosensitizers, including gold nanoparticles (GNPs), gold triethylphosphine cyanide ([Au(SCN) (PEt3)]), auranofin, ceria nanoparticles (CONPs), curcumin and its derivatives, piperlongamide, indolequinone derivatives, micheliolide, motexafin gadolinium, and ethane selenide selenidazole derivatives (SeDs), are meticulously elucidated in terms of their applications in radiotherapy. In this review, the sensitization mechanisms and the current research progress of these radiosensitizers are discussed in detail, with the overall aim of providing valuable insights for the judicious application of Trx system inhibitors in the field of cancer radiosensitization therapy.
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Affiliation(s)
- Yisheng Cao
- School of Pharmacy, State Key Laboratory of Applied Organic Chemistry, and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China
| | - Xiedong Zhou
- School of Pharmacy, State Key Laboratory of Applied Organic Chemistry, and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China
| | - Qiuying Nie
- School of Pharmacy, State Key Laboratory of Applied Organic Chemistry, and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China
| | - Junmin Zhang
- School of Pharmacy, State Key Laboratory of Applied Organic Chemistry, and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China.
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Rasouli M, Fattahi R, Nuoroozi G, Zarei-Behjani Z, Yaghoobi M, Hajmohammadi Z, Hosseinzadeh S. The role of oxygen tension in cell fate and regenerative medicine: implications of hypoxia/hyperoxia and free radicals. Cell Tissue Bank 2024; 25:195-215. [PMID: 37365484 DOI: 10.1007/s10561-023-10099-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 06/18/2023] [Indexed: 06/28/2023]
Abstract
Oxygen pressure plays an integral role in regulating various aspects of cellular biology. Cell metabolism, proliferation, morphology, senescence, metastasis, and angiogenesis are some instances that are affected by different tensions of oxygen. Hyperoxia or high oxygen concentration, enforces the production of reactive oxygen species (ROS) that disturbs physiological homeostasis, and consequently, in the absence of antioxidants, cells and tissues are directed to an undesired fate. On the other side, hypoxia or low oxygen concentration, impacts cell metabolism and fate strongly through inducing changes in the expression level of specific genes. Thus, understanding the precise mechanism and the extent of the implication of oxygen tension and ROS in biological events is crucial to maintaining the desired cell and tissue function for application in regenerative medicine strategies. Herein, a comprehensive literature review has been performed to find out the impacts of oxygen tensions on the various behaviors of cells or tissues.
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Affiliation(s)
- Mehdi Rasouli
- Student Research Committee, Department of Tissue Engineering and Applied Cell Science, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Roya Fattahi
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, 1985717443, Iran
| | - Ghader Nuoroozi
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, 1985717443, Iran
| | - Zeinab Zarei-Behjani
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maliheh Yaghoobi
- Engineering Department, Faculty of Chemical Engineering, Zanjan University, Zanjan, Iran
| | - Zeinab Hajmohammadi
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, 1985717443, Iran
| | - Simzar Hosseinzadeh
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, 1985717443, Iran.
- Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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10
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Filice M, Caferro A, Gattuso A, Sperone E, Agnisola C, Faggio C, Cerra MC, Imbrogno S. Effects of environmental hypoxia on the goldfish skeletal muscle: Focus on oxidative status and mitochondrial dynamics. JOURNAL OF CONTAMINANT HYDROLOGY 2024; 261:104299. [PMID: 38237486 DOI: 10.1016/j.jconhyd.2024.104299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 01/02/2024] [Accepted: 01/11/2024] [Indexed: 02/13/2024]
Abstract
The skeletal muscle is a highly plastic tissue. Its ability to respond to external stimuli and challenges allows it to face the functional needs of the organism. In the goldfish Carassius auratus, a model of hypoxia resistance, exposure to reduced oxygen is accompanied by an improvement of the swimming performance, relying on a sustained contractile behavior of the skeletal muscle. At the moment, limited information is available on the mechanisms underlying these responses. We here evaluated the effects of short- (4 days) and long- (20 days) term exposure to moderate water hypoxia on the goldfish white skeletal muscle, focusing on oxidative status and mitochondrial dynamics. No differences in lipid peroxidation, measured as 2-thiobarbituric acid-reacting substances (TBARS), and oxidatively modified proteins (OMP) were detected in animals exposed to hypoxia with respect to their normoxic counterparts. Exposure to short-term hypoxia was characterized by an enhanced SOD activity and expression, paralleled by increased levels of Nrf2, a regulator of the antioxidant cell response, and HSP70, a chaperone also acting as a redox sensor. The expression of markers of mitochondrial biogenesis (TFAM) and abundance (VDAC) and of the mtDNA/nDNA ratio was similar under normoxia and under both short- and long-term hypoxia, thus excluding a rearrangement of the mitochondrial apparatus. Only an increase of PGC1α (a transcription factor involved in mitochondrial dynamics) was detected after 20 days of hypoxia. Our results revealed novel aspects of the molecular mechanisms that in the goldfish skeletal muscle may sustain the response to hypoxia, thus contributing to adequate tissue function to organism requirements.
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Affiliation(s)
- Mariacristina Filice
- Dept. of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy
| | - Alessia Caferro
- Dept. of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy
| | - Alfonsina Gattuso
- Dept. of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy.
| | - Emilio Sperone
- Dept. of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy
| | - Claudio Agnisola
- Dept. of Biological Sciences, University of Naples Federico II, Napoli, Italy
| | - Caterina Faggio
- Dept. of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy; Dept. of Ecosustainable Marine Biotechnology, Stazione Zoologica Anton Dohrn, Naples, Italy.
| | - Maria Carmela Cerra
- Dept. of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy
| | - Sandra Imbrogno
- Dept. of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy
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11
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Li L, Pei Z, Wu R, Zhang Y, Pang Y, Hu H, Hu W, Geng Z, Feng T, Niu Y, Hao G, Zhang R. FDX1 regulates leydig cell ferroptosis mediates PM 2.5-induced testicular dysfunction of mice. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2023; 263:115309. [PMID: 37517308 DOI: 10.1016/j.ecoenv.2023.115309] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 07/24/2023] [Accepted: 07/25/2023] [Indexed: 08/01/2023]
Abstract
Epidemiological studies have established an association between chronic exposure to PM2.5 and male infertility. However, the underlying mechanisms were not fully revealed. In this study, we established mice models exposed to PM2.5 for 16 weeks, and a significant decrease in sperm quality accompanied by an increase in testosterone levels were observed after PM2.5 exposure. Moreover, treatment with ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor, effectively mitigated PM2.5-induced testicular dysfunction in mice. And lipid peroxidation and ferritin accumulation were found to be significantly increased in Leydig cells of testes with a PM2.5-dose dependent manner. Further investigations revealed that TM-3 cells, a mouse Leydig cell line, were prone to ferroptosis after PM2.5 exposure, and the cell viability was partly rescued after the intervention of Fer-1. Furthermore, our results supported that the ferroptosis of TM-3 cells was attributed to the upregulation of ferredoxin 1 (FDX1), which was the protein transferring electrons to cytochrome P450 family 11 subfamily A member 1 to aid lysing cholesterol to pregnenolone at initial of steroidogenesis. Mechanically, PM2.5-induced FDX1 upregulation resulted in cellular ROS elevation and ferrous iron overload, which together initiated an autoxidation process of polyunsaturated fatty acids in the cell membrane of Leydig cells until the accumulated lipid peroxides triggered ferroptotic cell death. Simultaneously, upregulation of FDX1 promoted steroidogenesis and let to an increased level of testosterone. In summary, our work suggested that FDX1, a mediator involving steroidogenesis, was a key regulator in PM2.5-induced Leydig cells ferroptosis.
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Affiliation(s)
- Lipeng Li
- Department of Toxicology, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China; Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang 050017, PR China
| | - Zijie Pei
- Department of Toxicology, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China; Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050017, PR China
| | - Ruiting Wu
- Department of Toxicology, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China
| | - Yaling Zhang
- Department of Toxicology, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China
| | - Yaxian Pang
- Department of Toxicology, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China
| | - Huaifang Hu
- Department of Toxicology, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China
| | - Wentao Hu
- Department of Toxicology, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China
| | - Zihan Geng
- Department of Occupational Health and Environmental Health, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China
| | - Tengfei Feng
- Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang 050017, PR China
| | - Yujie Niu
- Department of Occupational Health and Environmental Health, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China; Key Laboratory of Environment and Human Health, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China
| | - Guimin Hao
- Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang 050017, PR China.
| | - Rong Zhang
- Department of Toxicology, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China; Key Laboratory of Environment and Human Health, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China.
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12
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Lyu Y, Wang T, Huang S, Zhang Z. Mitochondrial Damage-Associated Molecular Patterns and Metabolism in the Regulation of Innate Immunity. J Innate Immun 2023; 15:665-679. [PMID: 37666239 PMCID: PMC10601681 DOI: 10.1159/000533602] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 08/10/2023] [Indexed: 09/06/2023] Open
Abstract
The innate immune system, as the host's first line of defense against intruders, plays a critical role in recognizing, identifying, and reacting to a wide range of microbial intruders. There is increasing evidence that mitochondrial stress is a major initiator of innate immune responses. When mitochondria's integrity is disrupted or dysfunction occurs, the mitochondria's contents are released into the cytosol. These contents, like reactive oxygen species, mitochondrial DNA, and double-stranded RNA, among others, act as damage-related molecular patterns (DAMPs) that can bind to multiple innate immune sensors, particularly pattern recognition receptors, thereby leading to inflammation. To avoid the production of DAMPs, in addition to safeguarding organelles integrity and functionality, mitochondria may activate mitophagy or apoptosis. Moreover, mitochondrial components and specific metabolic regulations modify properties of innate immune cells. These include macrophages, dendritic cells, innate lymphoid cells, and so on, in steady state or in stimulation that are involved in processes ranging from the tricarboxylic acid cycle to oxidative phosphorylation and fatty acid metabolism. Here we provide a brief summary of mitochondrial DAMPs' initiated and potentiated inflammatory response in the innate immune system. We also provide insights into how the state of activation, differentiation, and functional polarization of innate immune cells can be influenced by alteration to the metabolic pathways in mitochondria.
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Affiliation(s)
- Yanmin Lyu
- School of Clinical and Basic Medical Sciences, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Tianyu Wang
- School of Clinical and Basic Medical Sciences, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Shuhong Huang
- School of Clinical and Basic Medical Sciences, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Zhaoqiang Zhang
- School of Clinical and Basic Medical Sciences, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
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13
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Cancemi G, Cicero N, Allegra A, Gangemi S. Effect of Diet and Oxidative Stress in the Pathogenesis of Lymphoproliferative Disorders. Antioxidants (Basel) 2023; 12:1674. [PMID: 37759977 PMCID: PMC10525385 DOI: 10.3390/antiox12091674] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 08/19/2023] [Accepted: 08/25/2023] [Indexed: 09/29/2023] Open
Abstract
Lymphomas are a heterogeneous group of pathologies that result from clonal proliferation of lymphocytes. They are classified into Hodgkin lymphoma and non-Hodgkin lymphoma; the latter develops as a result of B, T, or NK cells undergoing malignant transformation. It is believed that diet can modulate cellular redox state and that oxidative stress is implicated in lymphomagenesis by acting on several biological mechanisms; in fact, oxidative stress can generate a state of chronic inflammation through the activation of various transcription factors, thereby increasing the production of proinflammatory cytokines and causing overstimulation of B lymphocytes in the production of antibodies and possible alterations in cellular DNA. The purpose of our work is to investigate the results of in vitro and in vivo studies on the possible interaction between lymphomas, oxidative stress, and diet. A variety of dietary regimens and substances introduced with the diet that may have antioxidant and antiproliferative effects were assessed. The possibility of using nutraceuticals as novel anticancer agents is discussed; although the use of natural substances in lymphoma therapy is an interesting field of study, further studies are needed to define the efficacy of different nutraceuticals before introducing them into clinical practice.
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Affiliation(s)
- Gabriella Cancemi
- Division of Hematology, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, Via Consolare Valeria, 98125 Messina, Italy; (G.C.); (A.A.)
| | - Nicola Cicero
- Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Via Consolare Valeria, 98125 Messina, Italy
| | - Alessandro Allegra
- Division of Hematology, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, Via Consolare Valeria, 98125 Messina, Italy; (G.C.); (A.A.)
| | - Sebastiano Gangemi
- Allergy and Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125 Messina, Italy;
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14
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Muita BK, Baxter SW. Temporal Exposure to Bt Insecticide Causes Oxidative Stress in Larval Midgut Tissue. Toxins (Basel) 2023; 15:toxins15050323. [PMID: 37235357 DOI: 10.3390/toxins15050323] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 04/27/2023] [Accepted: 05/01/2023] [Indexed: 05/28/2023] Open
Abstract
Bacillus thuringiensis (Bt) three-domain Cry toxins are highly successful biological pesticides; however, the mechanism through which they cause death to targeted larval midgut cells is not fully understood. Herein, we challenged transgenic Bt-susceptible Drosophila melanogaster larvae with moderate doses of activated Cry1Ac toxin and assessed the midgut tissues after one, three, and five hours using transmission electron microscopy and transcriptome sequencing. Larvae treated with Cry1Ac showed dramatic changes to their midgut morphology, including shortened microvilli, enlarged vacuoles, thickened peritrophic membranes, and swelling of the basal labyrinth, suggesting water influx. Transcriptome analysis showed that innate immune responses were repressed, genes involved with cell death pathways were largely unchanged, and mitochondria-related genes were strongly upregulated following toxin exposure. Defective mitochondria produced after toxin exposure were likely to contribute to significant levels of oxidative stress, which represent a common physiological response to a range of toxic chemicals. Significant reductions in both mitochondrial aconitase activity and ATP levels in the midgut tissue supported a rapid increase in reactive oxygen species (ROS) following exposure to Cry1Ac. Overall, these findings support the role of water influx, midgut cell swelling, and ROS activity in response to moderate concentrations of Cry1Ac.
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Affiliation(s)
- Biko K Muita
- School of Biological Sciences, University of Adelaide, Adelaide 5005, Australia
| | - Simon W Baxter
- School of BioSciences, University of Melbourne, Melbourne 3010, Australia
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15
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Nanoplatform-based cellular reactive oxygen species regulation for enhanced oncotherapy and tumor resistance alleviation. CHINESE CHEM LETT 2023. [DOI: 10.1016/j.cclet.2023.108300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/12/2023]
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16
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Bektas H, Algul S, Altindag F, Yegin K, Akdag MZ, Dasdag S. Effects of 3.5 GHz radiofrequency radiation on ghrelin, nesfatin-1, and irisin level in diabetic and healthy brains. J Chem Neuroanat 2022; 126:102168. [PMID: 36220504 DOI: 10.1016/j.jchemneu.2022.102168] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 10/04/2022] [Accepted: 10/04/2022] [Indexed: 12/15/2022]
Abstract
Diabetes, mobile phone use, and obesity have increased simultaneously in recent years. The radiofrequency radiation (RFR) emitted from mobile phones is largely absorbed in the heads of users. With 5 G, which has started to be used in some countries without the necessary precautions being taken, the amount of RFR to which living things are exposed will increase. In this study, the changes in energy homeostasis and redox balance caused by 5 G (3.5 GHz, GSM-modulated) were explored. The effects of RFR on the brains of diabetic and healthy rats were investigated and histopathological analysis was performed. Twenty-eight Wistar albino rats weighing 200-250 g were divided into 4 groups as sham, RFR, diabetes, and RFR+diabetes groups (n = 7). The rats in each group were kept in a plexiglass carousel for 2 h a day for 30 days. While the rats in the experimental groups were exposed to RFR for 2 h a day, the rats in the sham group were kept under the same experimental conditions but with the radiofrequency generator turned off. At the end of the experiment, brain tissues were collected from euthanized rats. Total antioxidant (TAS), total oxidant (TOS), hydrogen peroxide (H2O2), ghrelin, nesfatin-1, and irisin levels were determined. In addition, histopathological analyses of the brain tissues were performed. The specific absorption rate in the gray matter of the brain was calculated as 323 mW/kg and 195 mW/kg for 1 g and 10 g averaging, respectively. After RFR exposure among diabetic and healthy rats, decreased TAS levels and increased TOS and H2O2 levels were observed in brain tissues. RFR caused increases in ghrelin and irisin and a decrease in nesfatin-1 in the brain. It was also observed that RFR increased the number of degenerated neurons in the hippocampus. Our results indicate that 3.5 GHz RFR causes changes in the energy metabolism and appetite of both healthy and diabetic rats. Thus, 5 G may not be innocent in terms of its biological effects, especially in the presence of diabetes.
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Affiliation(s)
- Hava Bektas
- Department of Biophysics, Medical School of Van Yuzuncu Yil University, Van, Turkey
| | - Sermin Algul
- Department of Physiology, Medical School of Van Yuzuncu Yil University, Van, Turkey
| | - Fikret Altindag
- Department of Histology and Embryology, Medical School of Van Yuzuncu Yil University, Van, Turkey
| | - Korkut Yegin
- Department of Electrical and Electronics Engineering, Faculty of Engineering, Ege University, Turkey
| | - Mehmet Zulkuf Akdag
- Department of Biophysics, Medical School of Dicle University, Diyarbakır, Turkey
| | - Suleyman Dasdag
- Department of Biophysics, Medical School of Istanbul Medeniyet University, Istanbul, Turkey.
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17
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Christodoulou MC, Orellana Palacios JC, Hesami G, Jafarzadeh S, Lorenzo JM, Domínguez R, Moreno A, Hadidi M. Spectrophotometric Methods for Measurement of Antioxidant Activity in Food and Pharmaceuticals. Antioxidants (Basel) 2022; 11:2213. [PMID: 36358583 PMCID: PMC9686769 DOI: 10.3390/antiox11112213] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/01/2022] [Accepted: 11/04/2022] [Indexed: 07/30/2023] Open
Abstract
In recent years, there has been a growing interest in the application of antioxidants in food and pharmaceuticals due to their association with beneficial health effects against numerous oxidative-related human diseases. The antioxidant potential can be measured by various assays with specific mechanisms of action, including hydrogen atom transfer, single electron transfer, and targeted scavenging activities. Understanding the chemistry of mechanisms, advantages, and limitations of the methods is critical for the proper selection of techniques for the valid assessment of antioxidant activity in specific samples or conditions. There are various analytical techniques available for determining the antioxidant activity of biological samples, including food and plant extracts. The different methods are categorized into three main groups, such as spectrometry, chromatography, and electrochemistry techniques. Among these assays, spectrophotometric methods are considered the most common analytical technique for the determination of the antioxidant potential due to their sensitivity, rapidness, low cost, and reproducibility. This review covers the mechanism of actions and color changes that occur in each method. Furthermore, the advantages and limitations of spectrophotometric methods are described and discussed in this review.
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Affiliation(s)
| | - Jose C. Orellana Palacios
- Department of Organic Chemistry, Faculty of Chemical Sciences and Technologies, University of Castilla-La Mancha, 13071 Ciudad Real, Spain
| | - Golnaz Hesami
- Department of Food Science and Technology, Sanandaj Branch, Islamic Azad University, Pasdaran St., Sanandaj P.O. Box 618, Iran
| | - Shima Jafarzadeh
- School of Engineering, Edith Cowan University, Joondalup, WA 6027, Australia
| | - José M. Lorenzo
- Centro Tecnológico de la Carne de Galicia, Avd. Galicia N° 4, Parque Tecnológico de Galicia, San Cibrao das Viñas, 32900 Ourense, Spain
- Área de Tecnología de los Alimentos, Facultad de Ciencias de Ourense, Universidade de Vigo, 32004 Ourense, Spain
| | - Rubén Domínguez
- Centro Tecnológico de la Carne de Galicia, Avd. Galicia N° 4, Parque Tecnológico de Galicia, San Cibrao das Viñas, 32900 Ourense, Spain
| | - Andres Moreno
- Department of Organic Chemistry, Faculty of Chemical Sciences and Technologies, University of Castilla-La Mancha, 13071 Ciudad Real, Spain
| | - Milad Hadidi
- Department of Organic Chemistry, Faculty of Chemical Sciences and Technologies, University of Castilla-La Mancha, 13071 Ciudad Real, Spain
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18
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International Commission on the Biological Effects of Electromagnetic Fields (ICBE-EMF), Belyaev I, Blackman C, Chamberlin K, DeSalles A, Dasdag S, Fernández C, Hardell L, Héroux P, Kelley E, Kesari K, Maisch D, Mallery-Blythe E, Melnick RL, Miller A, Moskowitz JM, Sun W, Yakymenko I. Scientific evidence invalidates health assumptions underlying the FCC and ICNIRP exposure limit determinations for radiofrequency radiation: implications for 5G. Environ Health 2022; 21:92. [PMID: 36253855 PMCID: PMC9576312 DOI: 10.1186/s12940-022-00900-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 09/08/2022] [Indexed: 05/22/2023]
Abstract
In the late-1990s, the FCC and ICNIRP adopted radiofrequency radiation (RFR) exposure limits to protect the public and workers from adverse effects of RFR. These limits were based on results from behavioral studies conducted in the 1980s involving 40-60-minute exposures in 5 monkeys and 8 rats, and then applying arbitrary safety factors to an apparent threshold specific absorption rate (SAR) of 4 W/kg. The limits were also based on two major assumptions: any biological effects were due to excessive tissue heating and no effects would occur below the putative threshold SAR, as well as twelve assumptions that were not specified by either the FCC or ICNIRP. In this paper, we show how the past 25 years of extensive research on RFR demonstrates that the assumptions underlying the FCC's and ICNIRP's exposure limits are invalid and continue to present a public health harm. Adverse effects observed at exposures below the assumed threshold SAR include non-thermal induction of reactive oxygen species, DNA damage, cardiomyopathy, carcinogenicity, sperm damage, and neurological effects, including electromagnetic hypersensitivity. Also, multiple human studies have found statistically significant associations between RFR exposure and increased brain and thyroid cancer risk. Yet, in 2020, and in light of the body of evidence reviewed in this article, the FCC and ICNIRP reaffirmed the same limits that were established in the 1990s. Consequently, these exposure limits, which are based on false suppositions, do not adequately protect workers, children, hypersensitive individuals, and the general population from short-term or long-term RFR exposures. Thus, urgently needed are health protective exposure limits for humans and the environment. These limits must be based on scientific evidence rather than on erroneous assumptions, especially given the increasing worldwide exposures of people and the environment to RFR, including novel forms of radiation from 5G telecommunications for which there are no adequate health effects studies.
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19
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A Nile red-based near-infrared fluorescent probe for the detection of superoxide radical anion in living cells. CHINESE JOURNAL OF ANALYTICAL CHEMISTRY 2022. [DOI: 10.1016/j.cjac.2022.100140] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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20
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Targeting Redox Regulation as a Therapeutic Opportunity against Acute Leukemia: Pro-Oxidant Strategy or Antioxidant Approach? Antioxidants (Basel) 2022; 11:antiox11091696. [PMID: 36139768 PMCID: PMC9495346 DOI: 10.3390/antiox11091696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 08/07/2022] [Accepted: 08/26/2022] [Indexed: 11/17/2022] Open
Abstract
Redox adaptation is essential for human health, as the physiological quantities of non-radical reactive oxygen species operate as the main second messengers to regulate normal redox reactions by controlling several sensors. An abnormal increase reactive oxygen species, called oxidative stress, induces biological injury. For this reason, variations in oxidative stress continue to receive consideration as a possible approach to treat leukemic diseases. However, the intricacy of redox reactions and their effects might be a relevant obstacle; consequently, and alongside approaches aimed at increasing oxidative stress in neoplastic cells, antioxidant strategies have also been suggested for the same purpose. The present review focuses on the molecular processes of anomalous oxidative stress in acute myeloid and acute lymphoblastic leukemias as well as on the oxidative stress-determined pathways implicated in leukemogenic development. Furthermore, we review the effect of chemotherapies on oxidative stress and the possibility that their pharmacological effects might be increased by modifying the intracellular redox equilibrium through a pro-oxidant approach or an antioxidant strategy. Finally, we evaluated the prospect of varying oxidative stress as an efficacious modality to destroy chemoresistant cells using new methodologies. Altering redox conditions may be advantageous for inhibiting genomic variability and the eradication of leukemic clones will promote the treatment of leukemic disease.
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21
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Baykara S, Yıldırım H, Kazğan A, Tabara MF, Keleş DD, Gürok MG, Atmaca M. Retinal Changes in Panic Disorder Patients. Psychiatry Res Neuroimaging 2022; 324:111496. [PMID: 35690017 DOI: 10.1016/j.pscychresns.2022.111496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 05/06/2022] [Accepted: 05/16/2022] [Indexed: 10/18/2022]
Abstract
AIM Optical coherence tomography (OCT) is a novel method that allows high resolution cross-sectional imaging of biological tissues. It was suggested that changes in the cranial structure or functions would be reflected in the retina. OCT has been an important method in the diagnosis and follow-up of diseases via morphometric or quantitative retinal measurements. Panic disorder (PD) is an anxiety disorder, where free radicals, inflammatory processes and neurotransmitter transmission disorders play a role in the etiology. The present study aimed to demonstrate neurodegeneration in PD by the comparison of PD patient and control OCT data. MATERIAL AND METHOD The study group included 21 PD patients who met the study criteria. The control group included 21 healthy individuals without any known psychiatric or organic disease, including eye disease, and gender-matched to the patient group. All participants underwent detailed psychiatric and eye examinations. Central macular thickness (CMT), macular volume (MV), mean and retinal nerve fiber layer thickness (RNFL), ganglion cell layer thickness (GCLT), and central choroidal thickness (CCT) were measured in both eyes of all participants with OCT. A sociodemographic data form, Clinical Global Impression Scale (CGIS), and Panic Disorder Severity Scale (PDSS) were administered to the participants. RESULTS In the study, it was determined that the CMT values of the PD patients were lower when compared to the controls in the OCT examination. There was a statistically significant difference between the CMT of the PD patient group and the control group; the CMT was lower in the patient group. There were no significant differences between the groups based on GCLT, RNFL superior, RNFL inferior, RNFL nasal, RNFL temporal, and CCT. There was no significant correlation between CGIS, PDSS scores and OCT measurements. CONCLUSION This is the first study in the literature where patients with a PD diagnosis were analyzed based on the OCT method. OCT, which is a simple, noninvasive and relatively inexpensive method that the patient could easily adapt to during imaging, could be employed as a supplementary method in the diagnosis and follow-up of PD patients.
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Affiliation(s)
- Sema Baykara
- Fırat University, Faculty of Medicine, Department of Psychiatry, Elazig, Turkey.
| | - Hakan Yıldırım
- Fırat University, Faculty of Medicine, Department of Ophthalmology, Elazig, Turkey
| | - Aslı Kazğan
- Fırat University, Faculty of Medicine, Department of Psychiatry, Elazig, Turkey
| | | | | | - Mehmet Gürkan Gürok
- Fırat University, Faculty of Medicine, Department of Psychiatry, Elazig, Turkey
| | - Murad Atmaca
- Fırat University, Faculty of Medicine, Department of Psychiatry, Elazig, Turkey
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22
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Shannon N, Gravelle R, Cunniff B. Mitochondrial trafficking and redox/phosphorylation signaling supporting cell migration phenotypes. Front Mol Biosci 2022; 9:925755. [PMID: 35936783 PMCID: PMC9355248 DOI: 10.3389/fmolb.2022.925755] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 07/05/2022] [Indexed: 11/13/2022] Open
Abstract
Regulation of cell signaling cascades is critical in making sure the response is activated spatially and for a desired duration. Cell signaling cascades are spatially and temporally controlled through local protein phosphorylation events which are determined by the activation of specific kinases and/or inactivation of phosphatases to elicit a complete and thorough response. For example, A-kinase-anchoring proteins (AKAPs) contribute to the local regulated activity protein kinase A (PKA). The activity of kinases and phosphatases can also be regulated through redox-dependent cysteine modifications that mediate the activity of these proteins. A primary example of this is the activation of the epidermal growth factor receptor (EGFR) and the inactivation of the phosphatase and tensin homologue (PTEN) phosphatase by reactive oxygen species (ROS). Therefore, the local redox environment must play a critical role in the timing and magnitude of these events. Mitochondria are a primary source of ROS and energy (ATP) that contributes to redox-dependent signaling and ATP-dependent phosphorylation events, respectively. The strategic positioning of mitochondria within cells contributes to intracellular gradients of ROS and ATP, which have been shown to correlate with changes to protein redox and phosphorylation status driving downstream cellular processes. In this review, we will discuss the relationship between subcellular mitochondrial positioning and intracellular ROS and ATP gradients that support dynamic oxidation and phosphorylation signaling and resulting cellular effects, specifically associated with cell migration signaling.
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Affiliation(s)
- Nathaniel Shannon
- Department of Pathology and Laboratory Medicine, Redox Biology Program, University of Vermont Larner College of Medicine, Burlington, VT, United States
| | - Randi Gravelle
- Department of Pathology and Laboratory Medicine, Redox Biology Program, University of Vermont Larner College of Medicine, Burlington, VT, United States
| | - Brian Cunniff
- Department of Pathology and Laboratory Medicine, Redox Biology Program, University of Vermont Larner College of Medicine, Burlington, VT, United States
- University of Vermont Cancer Center, University of Vermont Larner College of Medicine, Burlington, VT, United States
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23
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Oshita M, Umeda K, Kataoka M, Azuma Y, Furuzono T. Continuous antimicrobial mechanism of dispersible hydroxyapatite nanoparticles doped with zinc ions for percutaneous device coatings. J Biomater Appl 2022; 37:659-667. [PMID: 35708097 DOI: 10.1177/08853282221108839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Percutaneous devices-indwelling catheters-related infections are serious clinical incidents. It is accordingly necessary to develop anti-infective coating materials suitable for the devices for long-term effectiveness. In our research group, highly dispersible and crystalline hydroxyapatite (HAp) nanoparticles doped with metallic or halogen ions possessing antibacterial activities have been developed. In this study, antibacterial, dispersible, and crystalline zinc (Zn)-doped hydroxyapatite [Zn(15)-HAp] nanoparticles substituted with 13.5% Zn content [Zn/(Zn + Ca) × 100] were prepared by a wet chemical method using an anti-sintering agent through calcination. Antibacterial activities of Zn(15)-HAp nanoparticles were evaluated using Escherichia coli (E. coli) and Staphylococcus aureus. The survival rates of the bacteria on Zn(15)-HAp nanoparticles were significantly lower than that on normal HAp (nHAp) coated surfaces, while no influences were observed on proliferation of L929 cells. Even after soaking Zn(15)-HAp nanoparticles in PBS for 2 weeks, the antibacterial activities against E. coli were maintained at a similar level to a 20 min soaking. The bacterial death was related to not only ion-exchange phenomenon between Zn and magnesium ions but also accumulation of reactive oxygen species (ROS) in the cells. Allergic-like reactions-anaphylactoid reactions-might not readily occur with Zn(15)-HAp nanoparticles because the amounts of histamine released from HMC-1 cells co-cultured with nanoparticles were not significantly different to that of nHAp, but were statistically much lower than that of chlorhexidine.
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Affiliation(s)
- Mari Oshita
- Biological System Engineering, 74014Graduate School of Biology Oriented Science and Technology, Kindai University, Kinokawa, Japan
| | - Koji Umeda
- Biological System Engineering, 74014Graduate School of Biology Oriented Science and Technology, Kindai University, Kinokawa, Japan
| | - Minami Kataoka
- Biological System Engineering, 74014Graduate School of Biology Oriented Science and Technology, Kindai University, Kinokawa, Japan
| | - Yoshinao Azuma
- Biotechnological Science, 74014Graduate School of Biology Oriented Science and Technology, Kindai University, Kinokawa, Japan
| | - Tsutomu Furuzono
- Biological System Engineering, 74014Graduate School of Biology Oriented Science and Technology, Kindai University, Kinokawa, Japan
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Ling MX, Nguyen M, McFaul CA, Lee RC. Peroxidation of tetronic 1107 reduces protein chaperone effect. Phys Biol 2022; 19. [PMID: 35545073 DOI: 10.1088/1478-3975/ac6eaf] [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: 08/06/2021] [Accepted: 05/11/2022] [Indexed: 11/12/2022]
Abstract
To enhance the stability of protein therapeutics, pharmaceutical companies have long used various copolymer surfactants as excipients. They act to stabilize proteins by adhering to the hydrophobic surface of the protein preventing denaturation and aggregation. However, some commonly used excipients possess polyoxyalkylene chains that are susceptible to oxidative degradation while in aqueous solution. We postulate that oxidation reactions involving the hydrophobic domains reduce the surfactant's ability to stabilize the native protein structure. We investigated the effect of UV (λ=254 nm) radiated Poloxamine T1107 (T1107) on its ability to disaggregate DTT denatured hen egg-white lysozyme (HEWL). Peroxidation of UV irradiated T1107 was analyzed using FTIR spectroscopy, the Fe+2 to Fe+3 ion reduction assay method, and 1H NMR. Our results indicate that increased UV irradiation led to structural changes in T1107, specifically the addition of a carbonyl on the formate group. The structural change decreased T1107's ability to disaggregate HEWL. These results indicate that peroxide content is an important parameter to control in polyoxyalkylene-based excipients.
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Affiliation(s)
- Michelle X Ling
- Plastic and Reconstructive Surgery, University of Chicago Biological Sciences Division, 5841 S. Maryland Ave., Chicago, Illinois, 60637-5416, UNITED STATES
| | - Michelle Nguyen
- Plastic and Reconstructive Surgery, University of Chicago Biological Sciences Division, 5841 S. Maryland Ave., Chicago, Illinois, 60637-5416, UNITED STATES
| | - Colin A McFaul
- Plastic and Reconstructive Surgery, University of Chicago Biological Sciences Division, 5841 S. Maryland Ave., Chicago, Illinois, 60637-5416, UNITED STATES
| | - Raphael C Lee
- Plastics and Reconstructive Surgery, University of Chicago Biological Sciences Division, 5841 S. Maryland Ave., Chicago, Illinois, 60637-5416, UNITED STATES
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ROS-Related miRNAs Regulate Immune Response and Chemoradiotherapy Sensitivity in Hepatocellular Carcinoma by Comprehensive Analysis and Experiment. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:4713518. [PMID: 35585886 PMCID: PMC9110211 DOI: 10.1155/2022/4713518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 04/09/2022] [Indexed: 11/28/2022]
Abstract
Reactive oxygen species (ROS) plays an essential role in the development of cancer. Here, we chose ROS-related miRNAs for consensus clustering analysis and ROS score construction. We find that ROS is extremely associated with prognosis, tumor immune microenvironment (TIME), gene mutations, N6-methyladenosine (m6A) methylation, and chemotherapy sensitivity in hepatocellular carcinoma (HCC). Mechanistically, ROS may affect the prognosis of HCC patients in numerous ways. Moreover, miR-210-3p and miR-106a-5p significantly increased the ROS level and stagnated cell cycle at G2/M in HCC; the results were more obvious in cells after ionizing radiation (IR). Finally, the two miRNAs suppressed cell proliferation, migration, and invasion and promoted apoptosis in huh7 and smmc7721 cells. It indicated that ROS might affect the prognosis of HCC patients through immune response and increase the sensitivity of HCC patients to radiotherapy and chemotherapy.
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Peres-Emidio EC, Freitas GJC, Costa MC, Gouveia-Eufrasio L, Silva LMV, Santos APN, Carmo PHF, Brito CB, Arifa RDN, Bastos RW, Ribeiro NQ, Oliveira LVN, Silva MF, Paixão TA, Saliba AM, Fagundes CT, Souza DG, Santos DA. Pseudomonas aeruginosa Infection Modulates the Immune Response and Increases Mice Resistance to Cryptococcus gattii. Front Cell Infect Microbiol 2022; 12:811474. [PMID: 35548467 PMCID: PMC9083911 DOI: 10.3389/fcimb.2022.811474] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 03/22/2022] [Indexed: 11/30/2022] Open
Abstract
Cryptococcosis is an invasive mycosis caused by Cryptococcus spp. that affects the lungs and the central nervous system (CNS). Due to the severity of the disease, it may occur concomitantly with other pathogens, as a coinfection. Pseudomonas aeruginosa (Pa), an opportunistic pathogen, can also cause pneumonia. In this work, we studied the interaction of C. gattii (Cg) and Pa, both in vitro and in vivo. Pa reduced growth of Cg by the secretion of inhibitory molecules in vitro. Macrophages previously stimulated with Pa presented increased fungicidal activity. In vivo, previous Pa infection reduced morbidity and delayed the lethality due to cryptococcosis. This phenotype was correlated with the decreased fungal burden in the lungs and brain, showing a delay of Cg translocation to the CNS. Also, there was increased production of IL-1β, CXCL-1, and IL-10, together with the influx of iNOS-positive macrophages and neutrophils to the lungs. Altogether, Pa turned the lung into a hostile environment to the growth of a secondary pathogen, making it difficult for the fungus to translocate to the CNS. Further, iNOS inhibition reverted the Pa protective phenotype, suggesting its
important role in the coinfection. Altogether, the primary Pa infection leads to balanced pro-inflammatory and anti-inflammatory responses during Cg infection. This response provided better control of cryptococcosis and was decisive for the mild evolution of the disease and prolonged survival of coinfected mice in a mechanism dependent on iNOS.
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Affiliation(s)
- Eluzia C. Peres-Emidio
- Departamento de Microbiologia/Laboratorio de Micologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Gustavo J. C. Freitas
- Departamento de Microbiologia/Laboratorio de Micologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Marliete C. Costa
- Departamento de Microbiologia/Laboratorio de Micologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Ludmila Gouveia-Eufrasio
- Departamento de Microbiologia/Laboratorio de Micologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Lívia M. V. Silva
- Departamento de Microbiologia/Laboratorio de Micologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Anderson P. N. Santos
- Departamento de Microbiologia/Laboratorio de Micologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Paulo H. F. Carmo
- Departamento de Microbiologia/Laboratorio de Micologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Camila B. Brito
- Departamento de Microbiologia/Laboratorio de Interação Microorganismo-Hospedeiro, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Raquel D. N. Arifa
- Departamento de Microbiologia/Laboratorio de Interação Microorganismo-Hospedeiro, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Rafael W. Bastos
- Faculdade de Ciencias Farmaceuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
- Centro de Biociencias, Universidade Federal do Rio Grande do Norte, Natal, Brazil
| | - Noelly Q. Ribeiro
- Departamento de Microbiologia/Laboratorio de Micologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Lorena V. N. Oliveira
- Departamento de Microbiologia/Laboratorio de Micologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Monique F. Silva
- Departamento de Patologia/Laboratorio de Patologia Celular e Molecular, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Tatiane A. Paixão
- Departamento de Patologia/Laboratorio de Patologia Celular e Molecular, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Alessandra M. Saliba
- Departamento de Microbiologia e Imunologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Caio T. Fagundes
- Departamento de Microbiologia/Laboratorio de Interação Microorganismo-Hospedeiro, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Daniele G. Souza
- Departamento de Microbiologia/Laboratorio de Interação Microorganismo-Hospedeiro, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Daniel A. Santos
- Departamento de Microbiologia/Laboratorio de Micologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
- *Correspondence: Daniel A. Santos, ;
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The SNPs of mitochondrial DNA displacement loop region and mitochondrial DNA copy number associated with risk of polymyositis and dermatomyositis. Sci Rep 2022; 12:5903. [PMID: 35393495 PMCID: PMC8990067 DOI: 10.1038/s41598-022-09943-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Accepted: 03/30/2022] [Indexed: 12/24/2022] Open
Abstract
Oxidative damage-induced mitochondrial dysfunction may activate muscle catabolism and autophagy pathways to initiate muscle weakening in idiopathic inflammatory myopathies (IIMs). In this study, Single nucleotide polymorphisms (SNPs) in the mitochondrial displacement loop (D-loop) and mitochondrial DNA (mtDNA) copy number were assessed and their association with the risk of polymyositis and dermatomyositis (PM/DM) was evaluated. Excessive D-loop SNPs (8.779 ± 1.912 vs. 7.972 ± 1.903, p = 0.004) correlated positively with mtDNA copy number (0.602 ± 0.457 vs. 0.300 ± 0.118, p < 0.001). Compared with that of the controls, the mtDNA of PM/DM patients showed D-loop SNP accumulation. In addition, the distribution frequencies of 16304C (p = 0.047) and 16519C (p = 0.043) were significantly higher in the patients with PM/DM. Subsequent analysis showed that reactive oxygen species (ROS) generation was increased in PM/DM patients compared with that in the controls (18,477.756 ± 13,574.916 vs. 14,484.191 ± 5703.097, p = 0.012). Further analysis showed that the PM/DM risk-related allele 16304C was significantly associated with lower IL-4 levels (p = 0.021), while 16519C had a trend to be associated with higher IL-2 expression (p = 0.064). The allele 16519C was associated with a positive antinuclear antibody (ANA) status in PM/DM patients (p = 0.011). Our findings suggest that mitochondrial D-loop SNPs could be potential biomarkers for PM/DM risk and these SNPs associated with cytokine expression may be involved in the development of PM/DM. Further, mtDNA copy number-mediated mitochondrial dysfunction may precede the onset of PM/DM.
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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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Kostka T, Ostberg-Potthoff JJ, Stärke J, Guigas C, Matsugo S, Mirčeski V, Stojanov L, Veličkovska SK, Winterhalter P, Esatbeyoglu T. Bioactive Phenolic Compounds from Lingonberry ( Vaccinium vitis-idaea L.): Extraction, Chemical Characterization, Fractionation and Cellular Antioxidant Activity. Antioxidants (Basel) 2022; 11:467. [PMID: 35326117 PMCID: PMC8944762 DOI: 10.3390/antiox11030467] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 02/22/2022] [Accepted: 02/24/2022] [Indexed: 02/07/2023] Open
Abstract
Lingonberries contain high contents of bioactive compounds such as chlorogenic acids and anthocyanins. In addition to radical scavenging and antioxidant activities, these compounds can protect cells from DNA damage. For this reason, lingonberries might be well suited for nutraceuticals or natural biomedicines. To assess these applications, the present study characterized and identified the most effective extract, only consisting of anthocyanins, copigments or a mixture of both, obtained from a lingonberry juice concentrate. An extract was generated by using a XAD-7 column followed by fractionation into anthocyanins and copigments using adsorptive membrane chromatography. After identification of main polyphenols by HPLC-photodiode array-electrospray ionization-tandem mass spectrometry, free radical scavenging activity was analyzed by electron spin resonance spectroscopy using 2,2-diphenyl-1-picrylhydrazyl and galvinoxyl radicals. Furthermore, cyclic voltammetry analyses and the Trolox equivalent antioxidant capacity (TEAC) assay were applied. Finally, the reactive oxygen species (ROS) reducing effects of the lingonberry extract and its fractions were evaluated in HepG2 cells. While the combination of anthocyanins and copigments possessed the highest antioxidant activities, all samples (XAD-7 extract, anthocyanin and copigment fraction) protected cells from oxidative stress. Thus, synergistic effects between phenolic compounds may be responsible for the high antioxidant potential of lingonberries, enabling their use as nutraceuticals.
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Affiliation(s)
- Tina Kostka
- Institute of Food Science and Human Nutrition, Gottfried Wilhelm Leibniz University Hannover, Am Kleinen Felde 30, 30167 Hannover, Germany
| | | | - Joachim Stärke
- Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Haid-und-Neu-Str. 9, 76131 Karlsruhe, Germany
| | - Claudia Guigas
- Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Haid-und-Neu-Str. 9, 76131 Karlsruhe, Germany
| | - Seiichi Matsugo
- School of Natural System, College of Science and Engineering, Kanazawa University, Kakuma-Machi, Kanazawa 920-1192, Japan
| | - Valentin Mirčeski
- Department of Inorganic and Analytical Chemistry, University of Lodz, Tamka 12, 91-403 Lodz, Poland
- Institute of Chemistry, Ss. Cyril and Methodius University, Arhimedova 5, 1000 Skopje, North Macedonia
| | - Leon Stojanov
- Institute of Chemistry, Ss. Cyril and Methodius University, Arhimedova 5, 1000 Skopje, North Macedonia
| | | | - Peter Winterhalter
- Institute of Food Chemistry, Technische Universität Braunschweig, Schleinitzstrasse 20, 38106 Braunschweig, Germany
| | - Tuba Esatbeyoglu
- Institute of Food Science and Human Nutrition, Gottfried Wilhelm Leibniz University Hannover, Am Kleinen Felde 30, 30167 Hannover, Germany
- Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Haid-und-Neu-Str. 9, 76131 Karlsruhe, Germany
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Araújo de Lima L, Oliveira Cunha PL, Felicio Calou IB, Tavares Neves KR, Facundo HT, Socorro de Barros Viana G. Effects of vitamin D (VD3) supplementation on the brain mitochondrial function of male rats, in the 6-OHDA-induced model of Parkinson's disease. Neurochem Int 2022; 154:105280. [PMID: 35026378 DOI: 10.1016/j.neuint.2022.105280] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 12/21/2021] [Accepted: 01/06/2022] [Indexed: 12/19/2022]
Abstract
Mitochondria dysfunction is an important factor involved in PD pathogenesis. We reported neuroprotective actions of vitamin D (VD3) on a PD model, and now we investigated the VD3 effects on the brain mitochondrial function. We focused on oxygen consumption, respiratory control ratio (RCR), ADP/O ratio, mitochondria swelling, H2O2 production, and SOD activity. Additionally, immunohistochemistry assays for the dopamine system markers (TH and DAT) and mitochondrial markers (VDAC1 and Hsp60) were also carried out in the striata. Young adult male Wistar rats (250 g, 2.5 months age) were anesthetized and subjected to stereotaxic surgery and injection of saline (SO group) or 6-OHDA, into the right striatum. Brain mitochondria were isolated from the groups: sham-operated (SO), 6-OHDA, 6-OHDA pretreated with VD3 for 7, days before the 6-OHDA lesion (6-OHDA+VD3, pre-) or treated with VD3 for 14 days, after the 6-OHDA lesion (6-OHDA+VD3, post-). VD3 prevented decreases in oxygen consumption, RCR, and ADP/O ratio observed after 6-OHDA injury. Noteworthy, a very low (oxygen consumption and RCR) or no improvement (ADP/O) were observed in the 6-OHDA+VD3 post- group. VD3 also prevented the increased mitochondria swelling and H2O2 production and a decrease in SOD activity, respectively, in the 6-OHDA injured mitochondria. Also, VD3 supplementation protected the hemiparkinsonian brain from decreases in TH and DAT expressions and decreased the upregulation of mitochondrial markers, as VDAC 1 and Hsp60. In conclusion, VD3 showed neuroprotective actions on brain mitochondria injured by 6-OHDA and should stimulate translational studies focusing on its use as a therapeutic strategy for the treatment of neurodegenerative diseases as PD.
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Resveratrol Hinders Postovulatory Aging by Modulating Oxidative Stress in Porcine Oocytes. Molecules 2021; 26:molecules26216346. [PMID: 34770755 PMCID: PMC8588440 DOI: 10.3390/molecules26216346] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 10/17/2021] [Accepted: 10/18/2021] [Indexed: 12/13/2022] Open
Abstract
Postovulatory aging of the mammalian oocytes causes deterioration of oocytes through several factors including oxidative stress. Keeping that in mind, we aimed to investigate the potential of a well-known antioxidant, resveratrol (RV), to evaluate the adverse effects of postovulatory aging in porcine oocytes. After in vitro maturation (IVM), a group of (25–30) oocytes (in three replicates) were exposed to 0, 1, 2, and 4 μmol/L of RV, respectively. The results revealed that the first polar body (PB1) extrusion rate of the oocytes significantly increased when the RV concentration reached up to 2 μmol/L (p < 0.05). Considering optimum RV concentration of 2 μmol/L, the potential of RV was evaluated in oocytes aged for 24 and 48 h. We used fluorescence microscopy to detect the relative level of reactive oxygen species (ROS), while GHS contents were measured through the enzymatic method. Our results revealed that aged groups (24 h and 48 h) treated with RV (2 μmol/L) showed higher (p < 0.05) ROS fluorescence intensity than the control group, but lower (p < 0.05) than untreated aged groups. The GSH content in untreated aged groups (24 h and 48 h) was lower (p < 0.05) than RV-treated groups, but both groups showed higher levels than the control. Similarly, the relative expression of the genes involved in antioxidant activity (CAT, GPXGSH-Px, and SOD1) in RV-treated groups was lower (p < 0.05) as compared to the control group but higher than that of untreated aged groups. Moreover, the relative mRNA expression of caspase-3 and Bax in RV-treated groups was higher (p < 0.05) than the control group but lower than untreated groups. Furthermore, the expression of Bcl-2 in the RV-treated group was significantly lower than control but higher than untreated aged groups. Taken together, our findings revealed that the RV can increase the expression of antioxidant genes by decreasing the level of ROS, and its potent antiapoptotic effects resisted against the decline in mitochondrial membrane potential in aged oocytes.
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Targeting Reactive Oxygen Species Capacity of Tumor Cells with Repurposed Drug as an Anticancer Therapy. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:8532940. [PMID: 34539975 PMCID: PMC8443364 DOI: 10.1155/2021/8532940] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 08/16/2021] [Indexed: 12/24/2022]
Abstract
Accumulating evidence shows that elevated levels of reactive oxygen species (ROS) are associated with cancer initiation, growth, and response to therapies. As concentrations increase, ROS influence cancer development in a paradoxical way, either triggering tumorigenesis and supporting the proliferation of cancer cells at moderate levels of ROS or causing cancer cell death at high levels of ROS. Thus, ROS can be considered an attractive target for therapy of cancer and two apparently contradictory but virtually complementary therapeutic strategies for the regulation of ROS to treat cancer. Despite tremendous resources being invested in prevention and treatment for cancer, cancer remains a leading cause of human deaths and brings a heavy burden to humans worldwide. Chemotherapy remains the key treatment for cancer therapy, but it produces harmful side effects. Meanwhile, the process of de novo development of new anticancer drugs generally needs increasing cost, long development cycle, and high risk of failure. The use of ROS-based repurposed drugs may be one of the promising ways to overcome current cancer treatment challenges. In this review, we briefly introduce the source and regulation of ROS and then focus on the status of repurposed drugs based on ROS regulation for cancer therapy and propose the challenges and direction of ROS-mediated cancer treatment.
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Tien Vo TT, Vo QC, Tuan VP, Wee Y, Cheng HC, Lee IT. The potentials of carbon monoxide-releasing molecules in cancer treatment: An outlook from ROS biology and medicine. Redox Biol 2021; 46:102124. [PMID: 34507160 PMCID: PMC8427320 DOI: 10.1016/j.redox.2021.102124] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 08/23/2021] [Accepted: 09/03/2021] [Indexed: 01/21/2023] Open
Abstract
Carbon monoxide (CO) is now well recognized a pivotal endogenous signaling molecule in mammalian lives. The proof-of-concept employing chemical carriers of exogenous CO as prodrugs for CO release, also known as CO-releasing molecules (CO-RMs), has been appreciated. The major advantage of CO-RMs is that they are able to deliver CO to the target sites in a controlled manner. There is an increasing body of experimental studies suggesting the therapeutic potentials of CO and CO-RMs in different cancer models. This review firstly presents a short but crucial view concerning the characteristics of CO and CO-RMs. Then, the anticancer activities of CO-RMs that target many cancer hallmarks, mainly proliferation, apoptosis, angiogenesis, and invasion and metastasis, are discussed. However, their anticancer activities are varying and cell-type specific. The aerobic metabolism of molecular oxygen inevitably generates various oxygen-containing reactive metabolites termed reactive oxygen species (ROS) which play important roles in both physiology and pathophysiology. Although ROS act as a double-edged sword in cancer, both sides of which may potentially have been exploited for therapeutic benefits. The main focus of the present review is thus to identify the possible signaling network by which CO-RMs can exert their anticancer actions, where ROS play the central role. Another important issue concerning the potential effect of CO-RMs on the aerobic glycolysis (the Warburg effect) which is a feature of cancer metabolic reprogramming is given before the conclusion with future prospects on the challenges of developing CO-RMs into clinically pharmaceutical candidates in cancer therapy.
CO-RMs as pro-drugs for controlled CO delivery are potentially beneficial in cancer treatment. Anticancer activities of CO-RMs are varying and cell-type specific. Anti-proliferative, pro-apoptotic, and anti-angiogenic effects are major niches. ROS may play a central role in the molecular pathways underlying anticancer activities of CO-RMs. CO-RMs can act against Warburg effect, a feature of cancer metabolic reprogramming.
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Affiliation(s)
- Thi Thuy Tien Vo
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - Quang Canh Vo
- Department of Dental Biomaterials Science, Dental Research Institute and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea
| | - Vo Phuoc Tuan
- Endoscopy Department, Cho Ray Hospital, Ho Chi Minh City, Viet Nam
| | - Yinshen Wee
- Department of Pathology, University of Utah, Salt Lake City, UT, USA
| | - Hsin-Chung Cheng
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan
| | - I-Ta Lee
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
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Sahoo BM, Banik BK, Borah P, Jain A. Reactive Oxygen Species (ROS): Key components in Cancer Therapies. Anticancer Agents Med Chem 2021; 22:215-222. [PMID: 34102991 DOI: 10.2174/1871520621666210608095512] [Citation(s) in RCA: 130] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 03/31/2021] [Accepted: 04/05/2021] [Indexed: 11/22/2022]
Abstract
Reactive oxygen species (ROS) refer to the highly reactive substances, which contain oxygen radicals. Hypochlorous acid, peroxides, superoxide, singlet oxygen, alpha-oxygen and hydroxyl radicals are the major examples of ROS. Generally, the reduction of oxygen (O2) in molecular form produces superoxide (•O2-) anion. ROS are produced during a variety of biochemical reactions within the cell organelles, such as endoplasmic reticulum, mitochondria and peroxisome. Naturally, ROS are also formed as a byproduct of the normal metabolism of oxygen. The production of ROS can be induced by various factors such as heavy metals, tobacco, smoke, drugs, xenobiotics, pollutants and radiation. From various experimental studies, it is reported that ROS act as either tumor suppressing or tumor promoting agent. The elevated levels of ROS can arrest the growth of tumor through the persistent increase in cell cycle inhibition. The increased level of ROS can induce apoptosis by both intrinsic and extrinsic pathways. ROS are considered to be tumor suppressing agent as the production of ROS is due to the use of most of the chemotherapeutic agents in order to activate the cell death. The cytotoxic effect of ROS provides impetus towards apoptosis, but in higher levels, ROS can cause initiation of malignancy that leads to uncontrolled cell death in cancer cells. Whereas, some species of ROS can influence various activities at the cellular level that include cell proliferation. This review highlights the genesis of ROS within cells by various routes and their role in cancer therapies.
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Affiliation(s)
- Biswa Mohan Sahoo
- Roland Institute of Pharmaceutical Sciences (Biju Patnaik University of Technology Nodal Centre of Research), Berhampur-760010, Odisha, India
| | - Bimal Krishna Banik
- Department of Mathematics and Natural Sciences, College of Sciences and Human Studies, Prince Mohammad Bin Fahd University, Al Khobar, Saudi Arabia
| | | | - Adya Jain
- Department of Chemistry, MRK Educational Institutions, IGU Rewari, Haryana, India
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35
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Disruption of insect immunity using analogs of the pleiotropic insect peptide hormone Neb-colloostatin: a nanotech approach for pest control II. Sci Rep 2021; 11:9459. [PMID: 33947876 PMCID: PMC8097067 DOI: 10.1038/s41598-021-87878-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 04/06/2021] [Indexed: 02/02/2023] Open
Abstract
This work continues our studies on the pleiotropic activity of the insect peptide Neb-colloostatin in insects. In vivo immunological bioassays demonstrated that hemocytotoxic analogs of Neb-colloostatin injected into Tenebrio molitor significantly reduced the number of hemocytes in the hemolymph and impaired phagocytosis, nodulation and phenoloxidase activities in the insects. Among the analogs tested, [Ala1]-,[Val1]-, [Hyp4]- and [Ach4]-colloostatin were particularly potent in disrupting cellular immunity in larvae, pupae and adult insects. This result suggests that the most effective analogs showed increases in the bioactivity period in the hemolymph of insects when compared to Neb-colloostatin. Recently, we demonstrated that it is possible to introduce Neb-colloostatin through the cuticle of an insect into the hemolymph when the peptide is coupled with nanodiamonds. In this study, we showed that [Ala1]-, [Val1]-, [Hyp4]- and [Ach4]-colloostatin, when complexed with nanodiamonds, may also pass through the cuticle into the hemolymph and induce long-term impairments of immunity in T. molitor at all developmental stages. Studies on the tissue selectivity and effectiveness of Neb-colloostatin analogs and efficient methods for their introduction into insects may contribute to the development of eco-friendly pest control methods based on bioactive peptidomimetics.
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Reid G, Klebe S, van Zandwijk N, George AM. Asbestos and Zeolites: from A to Z via a Common Ion. Chem Res Toxicol 2021; 34:936-951. [PMID: 33749247 DOI: 10.1021/acs.chemrestox.0c00286] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Asbestos and zeolites are silicate-based minerals, linked inextricably via paradoxical similarities and differences which have emanated from different geological epochs. Both have been employed in the service of humanity through millennia: asbestos, for its "inextinguishable" quality of being an insulator against heat and fire; zeolite, a "boiling stone" with its volcanic and marine sedimentary rock origins, for its propensity to adsorb water and remove metals and toxins. Serious adverse health effects observed in asbestos miners as long ago as the 1st Century AD did not halt the rising popularity of asbestos. As the miracle material of the 1900s, asbestos production and consumption exploded, culminating in its ubiquity in ships, vehicles, homes, commercial buildings, and over 3000 different industrial and household products. Through the 1940s and 1950s, epidemiological studies concluded that asbestos was a likely cause of asbestosis, lung cancer, and malignant mesothelioma, and it is now banned in many but far from all countries. The long latency between exposure to asbestos and the occurrence of cancer has obscured the deadly consequences of asbestos exposure for centuries. Even today, a considerable part of the world population is insufficiently aware of the dangers of asbestos, and millions of tons of this carcinogen continue to be mined and used worldwide. Zeolites, both natural and synthetic, are microporous aluminosilicate minerals commonly used in a myriad of processes, in the petrochemical industry, in domestic appliances and cleaning agents, as commercial adsorbents and exchangers for toxins and pollutants, and as catalysts. Zeolites are found in agriculture, veterinary science, and human health. More recently, new materials such as carbon nanotubes are being employed in materials requiring durability and thermal and electrical conductivity, yet nanotubes are now joining the ranks of more established particulates such as asbestos and silica, in causing human disease. In this review, we compare and contrast the similarities and differences of these two groups of silicate minerals and their waxing and waning use in the employ of humanity.
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Affiliation(s)
- Glen Reid
- Department of Pathology, Dunedin School of Medicine, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand
| | - Sonja Klebe
- Department of Anatomical Pathology, Flinders University and SA Pathology Bedford Park 5042, Australia
| | - Nico van Zandwijk
- Sydney Local Health District, Concord Repatriation General Hospital, Concord, New South Wales 2139, Australia
| | - Anthony M George
- School of Life Sciences, University of Technology Sydney, P.O. Box 123 Broadway, New South Wales 2007, Australia
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13 R,20-Dihydroxydocosahexaenoic Acid, a Novel Dihydroxy- DHA Derivative, Inhibits Breast Cancer Stemness through Regulation of the Stat3/IL-6 Signaling Pathway by Inducing ROS Production. Antioxidants (Basel) 2021; 10:antiox10030457. [PMID: 33804152 PMCID: PMC7999786 DOI: 10.3390/antiox10030457] [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: 01/18/2021] [Revised: 03/10/2021] [Accepted: 03/11/2021] [Indexed: 12/11/2022] Open
Abstract
Breast cancer is a major health problem worldwide. Cancer stem cells (CSCs) are known to mediate breast cancer metastasis and recurrence and are therefore a promising therapeutic target. In this study, we investigated the anti-inflammatory effect of 13R,20-dihydroxydocosahexaenoic acid (13R,20-diHDHA), a novel dihydroxy-DHA derivative, which was synthesized through an enzymatic reaction using cyanobacterial lipoxygenase. We found that 13R,20-diHDHA reduced the macrophage secretion of the inflammatory cytokines, IL-6 and TNF-α, and thus appeared to have anti-inflammatory effects. As the inflammatory tumor microenvironment is largely devoted to supporting the cancer stemness of breast cancer cells, we investigated the effect of 13R,20-diHDHA on breast cancer stemness. Indeed, 13R,20-diHDHA effectively inhibited breast cancer stemness, as evidenced by its ability to dose-dependently inhibit the mammospheres formation, colony formation, migration, and invasion of breast CSCs. 13R,20-diHDHA reduced the populations of CD44high/CD24low and aldehyde dehydrogenase (ALDH)-positive cells and the expression levels of the cancer stemness-related self-renewal genes, Nanog, Sox2, Oct4, c-Myc, and CD44. 13R,20-diHDHA increased reactive oxygen species (ROS) production, and the generated ROS reduced the phosphorylation of nuclear signal transducer and activator of transcription 3 (Stat3) and the secretion of IL-6 by mammospheres. These data collectively suggest that 13R,20-diHDHA inhibits breast cancer stemness through ROS production and downstream regulation of Stat3/IL-6 signaling, and thus might be developed as an anti-cancer agent acting against CSCs.
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Manoalide Shows Mutual Interaction between Cellular and Mitochondrial Reactive Species with Apoptosis in Oral Cancer Cells. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:6667355. [PMID: 33747349 PMCID: PMC7943270 DOI: 10.1155/2021/6667355] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 02/09/2021] [Accepted: 02/11/2021] [Indexed: 01/04/2023]
Abstract
We previously found that marine sponge-derived manoalide induced antiproliferation and apoptosis of oral cancer cells as well as reactive species generations probed by dichloro-dihydrofluorescein diacetate (DCFH-DA) and MitoSOX Red. However, the sources of cellular and mitochondrial redox stresses and the mutual interacting effects between these redox stresses and apoptosis remain unclear. To address this issue, we examined a panel of reactive species and used the inhibitors of cellular reactive species (N-acetylcysteine (NAC)), mitochondrial reactive species (MitoTEMPO), and apoptosis (Z-VAD-FMK; ZVAD) to explore their interactions in manoalide-treated oral cancer Ca9-22 and CAL 27 cells. Hydroxyl (˙OH), nitrogen dioxide (NO2˙), nitric oxide (˙NO), carbonate radical-anion (CO3 ˙-), peroxynitrite (ONOO-), and superoxide (O2 ˙-) were increased in oral cancer cells following manoalide treatments in terms of fluorescence staining and flow cytometry. Cellular reactive species (˙OH, NO2 ·, ˙NO, CO3 ˙-, and ONOO-) as well as cellular and mitochondrial reactive species (O2 ˙-) were induced in oral cancer cells following manoalide treatment for 6 h. NAC, MitoTEMPO, and ZVAD inhibit manoalide-induced apoptosis in terms of annexin V and pancaspase activity assays. Moreover, NAC inhibits mitochondrial reactive species and MitoTEMPO inhibits cellular reactive species, suggesting that cellular and mitochondrial reactive species can crosstalk to regulate each other. ZVAD shows suppressing effects on the generation of both cellular and mitochondrial reactive species. In conclusion, manoalide induces reciprocally activation between cellular and mitochondrial reactive species and apoptosis in oral cancer cells.
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Li G, Li Y, Xiao B, Cui D, Lin Y, Zeng J, Li J, Cao MJ, Liu J. Antioxidant Activity of Docosahexaenoic Acid (DHA) and Its Regulatory Roles in Mitochondria. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:1647-1655. [PMID: 33497204 DOI: 10.1021/acs.jafc.0c07751] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Reactive oxygen species (ROS) are single-electron-bearing oxidation-reduction products that are mainly produced in mitochondria. Excessive ROS accumulation may lead to oxidative damage. Docosahexaenoic acid (DHA) is an essential component of brain phospholipids and is mainly derived from the diet. Its antioxidant activities have been extensively studied. However, its regulatory roles in mitochondria and the underlying mechanism remain to be elucidated. In this study, the DHA's effect on cellular antioxidant capacity and mitochondrial functions was examined in HepG2 cells. The results showed that 100 μM DHA decreased cellular and mitochondrial ROS levels to 75.2 ± 9.4% (P < 0.05) and 55.1 ± 1.4% (P < 0.01), respectively. It also increased the total antioxidant capacity by 55.6 ± 0.1 and 49.2 ± 1.1% (P < 0.05), based on ABTS and FRAP assay results, respectively. Consistently, it increased the activities and gene expression of major antioxidant enzymes by at least 35 and 40% (P < 0.05), respectively. Furthermore, DHA promoted mitochondrial functions and biogenesis. These data suggested that DHA's antioxidant activity can be attributed to its enhancement of mitochondrial functions and biogenesis. This study may shed light on the molecular mechanisms underlying DHA's function in improving resistance to and relieving the symptoms of chronic disease.
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Affiliation(s)
- Guiling Li
- College of Food and Biological Engineering, Jimei University, No. 43 Yindou Road, Jimei District, Xiamen, Fujian 361021, P. R. China
- Fujian Marine Functional Food Engineering Technology Research Center, Xiamen, Fujian 361021, P. R. China
| | - Yuanyuan Li
- College of Food and Biological Engineering, Jimei University, No. 43 Yindou Road, Jimei District, Xiamen, Fujian 361021, P. R. China
- Fujian Marine Functional Food Engineering Technology Research Center, Xiamen, Fujian 361021, P. R. China
| | - Baoping Xiao
- College of Food and Biological Engineering, Jimei University, No. 43 Yindou Road, Jimei District, Xiamen, Fujian 361021, P. R. China
- Fujian Marine Functional Food Engineering Technology Research Center, Xiamen, Fujian 361021, P. R. China
| | - Dongyue Cui
- College of Food and Biological Engineering, Jimei University, No. 43 Yindou Road, Jimei District, Xiamen, Fujian 361021, P. R. China
- Fujian Marine Functional Food Engineering Technology Research Center, Xiamen, Fujian 361021, P. R. China
| | - Yanqi Lin
- College of Food and Biological Engineering, Jimei University, No. 43 Yindou Road, Jimei District, Xiamen, Fujian 361021, P. R. China
- Fujian Marine Functional Food Engineering Technology Research Center, Xiamen, Fujian 361021, P. R. China
| | - Jun Zeng
- College of Food and Biological Engineering, Jimei University, No. 43 Yindou Road, Jimei District, Xiamen, Fujian 361021, P. R. China
- Fujian Marine Functional Food Engineering Technology Research Center, Xiamen, Fujian 361021, P. R. China
| | - Jian Li
- College of Food and Biological Engineering, Jimei University, No. 43 Yindou Road, Jimei District, Xiamen, Fujian 361021, P. R. China
- Fujian Marine Functional Food Engineering Technology Research Center, Xiamen, Fujian 361021, P. R. China
| | - Min-Jie Cao
- College of Food and Biological Engineering, Jimei University, No. 43 Yindou Road, Jimei District, Xiamen, Fujian 361021, P. R. China
- Fujian Marine Functional Food Engineering Technology Research Center, Xiamen, Fujian 361021, P. R. China
| | - Jingwen Liu
- College of Food and Biological Engineering, Jimei University, No. 43 Yindou Road, Jimei District, Xiamen, Fujian 361021, P. R. China
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Touron J, Costes F, Coudeyre E, Perrault H, Richard R. Aerobic Metabolic Adaptations in Endurance Eccentric Exercise and Training: From Whole Body to Mitochondria. Front Physiol 2021; 11:596351. [PMID: 33584331 PMCID: PMC7873519 DOI: 10.3389/fphys.2020.596351] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 12/16/2020] [Indexed: 01/01/2023] Open
Abstract
A characteristic feature of eccentric as compared with concentric exercise is the ability to generate greater mechanical loads for lower cardiopulmonary demands. Current evidence concurs to show that eccentric training translates into considerable gains in muscle mass and strength. Less is known, however, regarding its impact on oxygen transport and on factors to be considered for optimizing its prescription and monitoring. This article reviews the existing evidence for endurance eccentric exercise effects on the components of the oxygen transport system from systemic to mitochondria in both humans and animals. In the studies reviewed, specially designed cycle-ergometers or downhill treadmill running were used to generate eccentric contractions. Observations to date indicate that overall, the aerobic demand associated with the eccentric training load was too low to significantly increase peak maximal oxygen consumption. By extension, it can be inferred that the very high eccentric power output that would have been required to solicit a metabolic demand sufficient to enhance peak aerobic power could not be tolerated or sustained by participants. The impact of endurance eccentric training on peripheral flow distribution remains largely undocumented. Given the high damage susceptibility of eccentric exercise, the extent to which skeletal muscle oxygen utilization adaptations would be seen depends on the balance of adverse and positive signals on mitochondrial integrity. The article examines the protection provided by repeated bouts of acute eccentric exercise and reports on the impact of eccentric cycling and downhill running training programs on markers of mitochondrial function and of mitochondrial biogenesis using mostly from animal studies. The summary of findings does not reveal an impact of training on skeletal muscle mitochondrial respiration nor on selected mitochondrial messenger RNA transcripts. The implications of observations to date are discussed within future perspectives for advancing research on endurance eccentric exercise physiological impacts and using a combined eccentric and concentric exercise approach to optimize functional capacity.
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Affiliation(s)
- Julianne Touron
- UCA–INRAE, Human Nutrition Unit, ASMS Team, University Clermont Auvergne, Clermont-Ferrand, France
| | - Frédéric Costes
- UCA–INRAE, Human Nutrition Unit, ASMS Team, University Clermont Auvergne, Clermont-Ferrand, France
- Service de Médecine du Sport et des Explorations Fonctionnelles, CHU Gabriel Montpied, Clermont-Ferrand, France
| | - Emmanuel Coudeyre
- UCA–INRAE, Human Nutrition Unit, ASMS Team, University Clermont Auvergne, Clermont-Ferrand, France
- Service de Médecine Physique et de Réadaptation, CHU Gabriel Montpied/CHU Louise Michel, Clermont-Ferrand, France
| | - Hélène Perrault
- Respiratory Division, McGill University Health Center, Montreal, QC, Canada
| | - Ruddy Richard
- UCA–INRAE, Human Nutrition Unit, ASMS Team, University Clermont Auvergne, Clermont-Ferrand, France
- Service de Médecine du Sport et des Explorations Fonctionnelles, CHU Gabriel Montpied, Clermont-Ferrand, France
- Unité d’Exploration en Nutrition (UEN), CRNH Auvergne, Clermont-Ferrand, France
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Oxidative stress and oral cavity cancer. Cancer 2021. [DOI: 10.1016/b978-0-12-819547-5.00006-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Raslan MA, F. Taher R, Al-Karmalawy AA, El-Ebeedy D, Metwaly AG, Elkateeb NM, Ghanem A, Elghaish RA, Abd El Maksoud AI. Cordyline fruticosa(L.) A. Chev. leaves: isolation, HPLC/MS profiling and evaluation of nephroprotective and hepatoprotective activities supported by molecular docking. NEW J CHEM 2021; 45:22216-22233. [DOI: 10.1039/d1nj02663a] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The metabolites profile ofC. fruticosa(L.) A. Chev. leaves, 12 isolates, and its nephroprotective and hepatoprotective activities are described.
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Affiliation(s)
- Mona A. Raslan
- Pharmacognosy Department, National Research Centre, Dokki, 12622 Giza, Egypt
| | - Rehab F. Taher
- Chemistry of Natural Compounds Department, National Research Centre, 12622 Giza, Egypt
| | - Ahmed A. Al-Karmalawy
- Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt
| | - Dalia El-Ebeedy
- Pharmaceutical Biotechnology Department, Faculty of Biotechnology, Misr University for Science and Technology, Giza, Egypt
| | | | | | - Aml Ghanem
- Faculty of biotechnology, Badr university, Cairo, Egypt
| | | | - Ahmed I. Abd El Maksoud
- Industrial Biotechnology Department, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Sadat City, Egypt
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Ramos-Tovar E, Muriel P. Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver. Antioxidants (Basel) 2020; 9:E1279. [PMID: 33333846 PMCID: PMC7765317 DOI: 10.3390/antiox9121279] [Citation(s) in RCA: 170] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 12/03/2020] [Accepted: 12/11/2020] [Indexed: 12/11/2022] Open
Abstract
Activated hepatic stellate cells (HSCs) and myofibroblasts are the main producers of extracellular matrix (ECM) proteins that form the fibrotic tissue that leads to hepatic fibrosis. Reactive oxygen species (ROS) can directly activate HSCs or induce inflammation or programmed cell death, especially pyroptosis, in hepatocytes, which in turn activates HSCs and fibroblasts to produce ECM proteins. Therefore, antioxidants and the nuclear factor E2-related factor-2 signaling pathway play critical roles in modulating the profibrogenic response. The master proinflammatory factors nuclear factor-κB (NF-κB) and the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome may coordinate to produce and activate profibrogenic molecules such as interleukins 1β and 18, which effectively activate HSCs, to produce large amounts of fibrotic proteins. Furthermore, the NLRP3 inflammasome activates pro-caspase 1, which is upregulated by NF-κB, to produce caspase 1, which induces pyroptosis via gasdermin and the activation of HSCs. ROS play central roles in the activation of the NF-κB and NLRP3 signaling pathways via IκB (an inhibitor of NF-κB) and thioredoxin-interacting protein, respectively, thereby linking the molecular mechanisms of oxidative stress, inflammation and fibrosis. Elucidating these molecular pathways may pave the way for the development of therapeutic tools to interfere with specific targets.
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Affiliation(s)
- Erika Ramos-Tovar
- Postgraduate Studies and Research Section, School of Higher Education in Medicine-IPN, Plan de San Luis y Díaz Mirón s/n, Casco de Santo Tomás, Mexico City 11340, Mexico;
| | - Pablo Muriel
- Laboratory of Experimental Hepatology, Department of Pharmacology, Cinvestav-IPN, Av. Instituto Politécnico Nacional 2508, Apartado Postal 14-740, Mexico City 07000, Mexico
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Kaweme NM, Zhou S, Changwe GJ, Zhou F. The significant role of redox system in myeloid leukemia: from pathogenesis to therapeutic applications. Biomark Res 2020; 8:63. [PMID: 33292641 PMCID: PMC7661181 DOI: 10.1186/s40364-020-00242-z] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Accepted: 10/29/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Excessive generation of reactive oxygen species (ROS) in the presence of a defective antioxidant system can induce cellular damage and disrupt normal physiological functions. Several studies have revealed the unfavorable role of ROS in promoting the growth, proliferation, migration, and survival of leukemia cells. In this review study, we summarize the mechanisms of ROS production and its role in leukemogenesis, counteractive effects of antioxidants, and implicate the current ROS-dependent anticancer therapies in acute myeloid leukemia. BODY: The dysregulation of the redox system is known to play a significant role in the pathogenesis of leukemia. Leukemia cells generate high levels of ROS, which further increases the levels through extra pathways, including mitochondrial deoxyribonucleic mutation, leukemic oncogene activation, increased nicotinamide adenine phosphate hydrogen (NADPH), and cytochrome P450 activities. Aforementioned pathways once activated have shown to promote genomic instability, induce drug resistance to leukemia medical therapy, disease relapse and reduce survival period. The current standard of treatment with chemotherapy employs the pro-oxidant approach to induce apoptosis and promote tumor regression. However, this approach retains several deleterious effects on the subject resulting in degradation of the quality of life. Nevertheless, the addition of an antioxidant as an adjuvant drug to chemotherapy alleviates treatment-related toxicity, increases chemotherapeutic efficacy, and improves survival rates of a patient. CONCLUSION Acute myeloid leukemia remains a daunting challenge to clinicians. The desire to achieve the maximum benefit of chemotherapy but also improve patient outcomes is investigated. ROS generated through several pathways promotes leukemogenesis, drug resistance, and disease relapse. Chemotherapy, the mainstay of treatment, further upregulates ROS levels. Therefore, the addition of an antioxidant to leukemia medical therapy alleviates toxicity and improves patient outcomes.
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Affiliation(s)
- Natasha Mupeta Kaweme
- Department of Hematology, Zhongnan Hospital affiliated to Wuhan University, No. 169 Donghu road, 430071, Wuhan, P.R. China
| | - Shu Zhou
- Department of Hematology, Zhongnan Hospital affiliated to Wuhan University, No. 169 Donghu road, 430071, Wuhan, P.R. China
| | - Geoffrey Joseph Changwe
- School of Medicine, Shandong University, No. 44, Wenhua West Road, Jinan, 250012, P.R. China
| | - Fuling Zhou
- Department of Hematology, Zhongnan Hospital affiliated to Wuhan University, No. 169 Donghu road, 430071, Wuhan, P.R. China.
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Role of Nrf2 and mitochondria in cancer stem cells; in carcinogenesis, tumor progression, and chemoresistance. Biochimie 2020; 179:32-45. [PMID: 32946993 DOI: 10.1016/j.biochi.2020.09.014] [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: 01/24/2020] [Revised: 08/05/2020] [Accepted: 09/04/2020] [Indexed: 02/06/2023]
Abstract
Cancer stem cells (CSCs) are rare sub-population in tumor mass with self-renewal and differentiation abilities; CSCs are considered as the main cells which are responsible for tumor metastasis, cancer recurrence, and chemo/radio-resistance. CSCs are believed to contain low mitochondria in quantity, high concentration of nuclear factor erythroid 2-related factor 2 (Nrf2), and low reactive oxygen species (ROS) levels. Mitochondria regulate certain cellular functions, including controlling of cellular energetics, calcium signaling, cell growth and cell differentiation, cell cycle regulation, and cell death. Also, mitochondria are the main sources of intrinsic ROS production. Dysfunction of CSCs mitochondria due to oxidative phosphorylation is reported in several pathological conditions, including metabolic disorders, age-related diseases, and various types of cancers. ROS levels play a significant role in cellular signal transduction and CSCs' identity and differentiation capability. Nrf2 is a master transcription factor that plays critical functions in maintaining cellular redox hemostasis by regulating several antioxidant and detoxification pathways. Recently, the critical function of Nrf2 in CSCs has been revealed by several studies. Nrf2 is an essential molecule in the maintenance of CSCs' stemness and self-renewal in response to different oxidative stresses such as chemotherapy-induced elevation of ROS. Nrf2 enables these cells to recover from chemotherapy damages, and promotes establishment of invasion and dissemination. In this study, we have summarized the role of Nrf2 and mitochondria function CSCs, which promote cancer development. The significant role of Nrf2 in the regulation of mitochondrial function and ROS levels suggests this molecule as a potential target to eradicate CSCs.
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Figueroa D, Signore A, Araneda O, Contreras HR, Concha M, García C. Toxicity and differential oxidative stress effects on zebrafish larvae following exposure to toxins from the okadaic acid group. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2020; 83:573-588. [PMID: 32686606 DOI: 10.1080/15287394.2020.1793046] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Okadaic acid-group (OA-group) is a set of lipophilic toxins produced only in seawater by species of the Dinophysis and Prorocentrum genera, and characterized globally by being associated with harmful algal blooms (HABs). The diarrhetic shellfish poisoning toxins okadaic acid (OA) and dinophysistoxin-1 (DTX-1) are the most prevalent toxic analogues making up the OA-group, which jeopardize environmental safety and human health through consumption of hydrobiological organisms contaminated with these toxins that produce diarrhetic shellfish poisoning (DSP) syndrome in humans. Consequently, a regulatory limit of 160 μg of OA-group/kg was established for marine resources (bivalves). The aim of this study was to investigate effects varying concentrations of 1-15 μg/ml OA or DTX-1 on toxicity, development, and oxidative damage in zebrafish larvae (Danio rerio). After determining the lethal concentration 50 (LC50) in zebrafish larvae of 10 and 7 μg/ml (24 h) and effective concentration 50 (EC50) of 8 and 6 μg/ml (24 h), different concentrations (5, 6.5, or 8 μg/ml of OA and 4, 4.5, or 6 μg/ml of DTX-1) were used to examine the effects of these toxins on oxidative damage to larvae at different time points between 24 and 120 hpf. Macroscopic evaluation during the exposure period showed alterations in zebrafish including pericardial edema, cyclopia, shortening in the anteroposterior axis, and developmental delay. The activity levels of biochemical biomarkers superoxide dismutase (SOD) and catalase (CAT) demonstrated a concentration-dependent decrease while glutathione peroxidase (GPx) and glutathione reductase (GR) were markedly elevated. In addition, increased levels of oxidative damage (malondialdehyde and carbonyl content) were detected following toxin exposure. Data demonstrate that high concentrations of OA and DTX-1produced pathological damage in the early stages of development <48 h post-fertilization (hpf) associated with oxidative damage.
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Affiliation(s)
- Diego Figueroa
- Laboratory of Marine Toxins, Physiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad De Chile , Santiago, Chile
| | - Ailen Signore
- Anatomy and Developmental Biology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad De Chile , Santiago, Chile
| | - Oscar Araneda
- Integrative Laboratory of Biomechanics and Physiology of Effort, Kinesiology School, Faculty of Medicine, Universidad De Los Andes , Santiago, Chile
| | - Héctor R Contreras
- Department of Basic and Clinical Oncology, Faculty of Medicine, Universidad De Chile , Santiago, Chile
| | - Miguel Concha
- Anatomy and Developmental Biology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad De Chile , Santiago, Chile
| | - Carlos García
- Laboratory of Marine Toxins, Physiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad De Chile , Santiago, Chile
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Boguszewska K, Szewczuk M, Kaźmierczak-Barańska J, Karwowski BT. The Similarities between Human Mitochondria and Bacteria in the Context of Structure, Genome, and Base Excision Repair System. Molecules 2020; 25:E2857. [PMID: 32575813 PMCID: PMC7356350 DOI: 10.3390/molecules25122857] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 06/17/2020] [Accepted: 06/19/2020] [Indexed: 02/06/2023] Open
Abstract
Mitochondria emerged from bacterial ancestors during endosymbiosis and are crucial for cellular processes such as energy production and homeostasis, stress responses, cell survival, and more. They are the site of aerobic respiration and adenosine triphosphate (ATP) production in eukaryotes. However, oxidative phosphorylation (OXPHOS) is also the source of reactive oxygen species (ROS), which are both important and dangerous for the cell. Human mitochondria contain mitochondrial DNA (mtDNA), and its integrity may be endangered by the action of ROS. Fortunately, human mitochondria have repair mechanisms that allow protecting mtDNA and repairing lesions that may contribute to the occurrence of mutations. Mutagenesis of the mitochondrial genome may manifest in the form of pathological states such as mitochondrial, neurodegenerative, and/or cardiovascular diseases, premature aging, and cancer. The review describes the mitochondrial structure, genome, and the main mitochondrial repair mechanism (base excision repair (BER)) of oxidative lesions in the context of common features between human mitochondria and bacteria. The authors present a holistic view of the similarities of mitochondria and bacteria to show that bacteria may be an interesting experimental model for studying mitochondrial diseases, especially those where the mechanism of DNA repair is impaired.
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Affiliation(s)
| | | | | | - Bolesław T. Karwowski
- DNA Damage Laboratory of Food Science Department, Faculty of Pharmacy, Medical University of Lodz, ul. Muszynskiego 1, 90-151 Lodz, Poland; (K.B.); (M.S.); (J.K.-B.)
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48
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Panahi M, Rahimi B, Rahimi G, Yew Low T, Saraygord-Afshari N, Alizadeh E. Cytoprotective effects of antioxidant supplementation on mesenchymal stem cell therapy. J Cell Physiol 2020; 235:6462-6495. [PMID: 32239727 DOI: 10.1002/jcp.29660] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 02/15/2020] [Indexed: 12/11/2022]
Abstract
Mesenchymal stem cells (MSCs) are earmarked as perfect candidates for cell therapy and tissue engineering due to their capacity to differentiate into different cell types. However, their potential for application in regenerative medicine declines when the levels of the reactive oxygen and nitrogen species (RONS) increase from the physiological levels, a phenomenon which is at least inevitable in ex vivo cultures and air-exposed damaged tissues. Increased levels of RONS can alter the patterns of osteogenic and adipogenic differentiation and inhibit proliferation, as well. Besides, oxidative stress enhances senescence and cell death, thus lowering the success rates of the MSC engraftment. Hence, in this review, we have selected some representatives of antioxidants and newly emerged nano antioxidants in three main categories, including chemical compounds, biometabolites, and protein precursors/proteins, which are proved to be effective in the treatment of MSCs. We will focus on how antioxidants can be applied to optimize the clinical usage of the MSCs and their associated signaling pathways. We have also reviewed several paralleled properties of some antioxidants and nano antioxidants which can be simultaneously used in real-time imaging, scaffolding techniques, and other applications in addition to their primary antioxidative function.
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Affiliation(s)
- Mohammad Panahi
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Bahareh Rahimi
- Department of Medical Biotechnology, Faculty of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Golbarg Rahimi
- Department of Cellular and Molecular Biology, University of Esfahan, Esfahan, Iran
| | - Teck Yew Low
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Neda Saraygord-Afshari
- Department of Medical Biotechnology, Faculty of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Effat Alizadeh
- Drug Applied Research Center and Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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Effect of memantine hydrochloride on cisplatin-induced neurobehavioral toxicity in mice. Acta Neurol Belg 2020; 120:71-82. [PMID: 31190140 DOI: 10.1007/s13760-019-01161-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2018] [Accepted: 06/04/2019] [Indexed: 01/19/2023]
Abstract
Cisplatin is an anticancer agent widely used in the treatment of malignant tumors. One of the major adverse effects of cisplatin is its neurotoxicity. Memantine, an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, has been reported to have neuroprotective effects against neurological deficits. This study therefore investigated the possible protective role of memantine as an agent to minimize the neurobehavioral toxic side effects of cisplatin. Two different therapeutic doses of memantine (5 mg/kg) and (10 mg/kg) were orally administered for 30 days to 50 male BALB/c mice divided into 5 groups: G1: no treatment; G2: cisplatin treatment; G3: memantine treatment; G4: pretreatment of (5 mg/kg) memantine with cisplatin (4 mg/kg); G5: pretreatment of 10 mg/kg memantine with cisplatin (4 mg/kg). Weekly neurobehavioral investigations were conducted using the following battery of tests: open field activity, negative geotaxis, hole-board test, swimming test, and calculation of weight. At the end of the experimental period the mice were euthanized, and immunohistochemistry was then used to measure the expression scores of nicotinic acetylcholine receptors (nAChRs) in the muscles and brain. Results revealed that mice in G2 showed a significant decrease in the ability to perform neurobehavioral tasks. The mice in G5 exhibited a significantly improved ability on these tests, indicating a complete neurobehavioral protective effect, while the mice in G4 showed partial protection. The nAChRs score showed higher expression in the case of G2 in comparison with G3, G4, and G5. Weight loss was exhibited in G2, while in G3 and G1 these values were normal. A therapeutic dose of memantine 10 mg/kg yielded more protection than 5 mg/kg in the treatment of neuropathy; this highlights the importance of using memantine to decrease the main side effects of cisplatin.
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Li Q, Tian M, Teng J, Gao P, Tang BQ, Wu H. Radio frequency-induced superoxide accumulation affected the growth and viability of Saccharomyces cerevisiae. Int Microbiol 2020; 23:391-396. [PMID: 31898034 DOI: 10.1007/s10123-019-00111-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 11/24/2019] [Accepted: 11/29/2019] [Indexed: 12/26/2022]
Abstract
With the development of the electric technologies, the biological effects of electromagnetic fields (EMF) were widely studied. However, the results remain controversial and the biophysical mechanisms are still unknown. To our knowledge, little studies pay attention to the radio frequency (RF) of 2.6-5 MHz. In the present study, we investigated the effect of these radio frequencies on the growth and cell viability of Saccharomyces cerevisiae at very low power density below 0.1 mT. The result appeared to be time-dependent. The growth of the yeast cells was obviously affected by the RF-EMF with a 43.5% increase when exposed for 30 h, and the growth-promoting effect decreased along with the radiation time and eventually turned to an inhibiting effect retarding growth by 20.7% at 89 h. The cell viability was improved to 70.1% at 8 h and reduced by 33.5% at 28 h. The superoxide accumulated in exposed cells as radiation time increased which may lead to the inhibition of viability and growth of the cells. However, the efficient frequency, power density, and exposure dosage await further investigation. Nevertheless, the wave band studied in this research is effective to produce biological effect, and therefore, it may provide an optional new radio frequency which is valuable for the development and utilization in therapy technique and medical use.
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Affiliation(s)
- Qing Li
- Institute of Life Science & Technology, ENN Group, South District of ENN Industrial Park, Langfang, 065001, Hebei, China
| | - Miao Tian
- Institute of Life Science & Technology, ENN Group, South District of ENN Industrial Park, Langfang, 065001, Hebei, China
| | - Jie Teng
- Institute of Life Science & Technology, ENN Group, South District of ENN Industrial Park, Langfang, 065001, Hebei, China
| | - Peng Gao
- Institute of Life Science & Technology, ENN Group, South District of ENN Industrial Park, Langfang, 065001, Hebei, China
| | - Bruce Qing Tang
- Institute of Life Science & Technology, ENN Group, South District of ENN Industrial Park, Langfang, 065001, Hebei, China
| | - Hong Wu
- Institute of Life Science & Technology, ENN Group, South District of ENN Industrial Park, Langfang, 065001, Hebei, China.
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