Repository of Research and Investigative Information

Repository of Research and Investigative Information

دانشگاه علوم پزشکی و خدمات بهداشتی درمانی زنجان

Mitochondrial oxidative stress and dysfunction induced by isoniazid: study on isolated rat liver and brain mitochondria

(2016) Mitochondrial oxidative stress and dysfunction induced by isoniazid: study on isolated rat liver and brain mitochondria. Drug and Chemical Toxicology. pp. 224-32. ISSN 1525-6014 (Electronic) 0148-0545 (Linking)

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Abstract

Isoniazid (INH or isonicotinic hydrazide) is used for the treatment and prophylaxis of tuberculosis. Liver and brain are two important target organs in INH toxicity. However, the exact mechanisms behind the INH hepatotoxicity or neurotoxicity have not yet been completely understood. Considering the mitochondria as one of the possible molecular targets for INH toxicity, the aim of this study was to evaluate the mechanisms of INH mitochondrial toxicity on isolated mitochondria. Mitochondria were isolated by differential ultracentrifugation from male Sprague-Dawley rats and incubated with different concentrations of INH (25-2000 muM) for the investigation of mitochondrial parameters. The results indicated that INH could interact with mitochondrial respiratory chain and inhibit its activity. Our results showed an elevation in mitochondrial reactive oxygen species (ROS) formation, lipid peroxidation and mitochondrial membrane potential collapse after exposure of isolated liver mitochondria in INH. However, different results were obtained in brain mitochondria. Noteworthy, significant glutathione oxidation, adenosine triphosphate (ATP) depletion and lipid peroxidation were observed in higher concentration of INH, as compared to liver mitochondria. In conclusion, our results suggest that INH may initiate its toxicity in liver mitochondria through interaction with electron transfer chain, lipid peroxidation, mitochondrial membrane potential decline and cytochrome c expulsion which ultimately lead to cell death signaling.

Item Type: Article
Keywords: Animals Antitubercular Agents/*toxicity Brain/*drug effects/metabolism In Vitro Techniques Isoniazid/*toxicity Lipid Peroxidation/drug effects Liver/*drug effects/metabolism Male Membrane Potential, Mitochondrial/drug effects Mitochondria/*drug effects/metabolism Mitochondria, Liver/drug effects/metabolism Mitochondrial Swelling/drug effects Oxidative Stress/*drug effects Rats, Sprague-Dawley Reactive Oxygen Species/metabolism Isoniazid (INH) isolated mitochondria mechanistic toxicity
Page Range: pp. 224-32
Journal or Publication Title: Drug and Chemical Toxicology
Abstract and Indexing: ISI, Pubmed, Scopus
Quartile : Q4
Volume: 39
Number: 2
Identification Number: https://doi.org/10.3109/01480545.2015.1092039
ISSN: 1525-6014 (Electronic) 0148-0545 (Linking)
Depositing User: خانم مریم زرقانی
URI: http://repository.zums.ac.ir/id/eprint/721

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