Repository of Research and Investigative Information

Repository of Research and Investigative Information

دانشگاه علوم پزشکی و خدمات بهداشتی درمانی زنجان

Toxicity of valproic acid in isolated rat liver mitochondria

(2013) Toxicity of valproic acid in isolated rat liver mitochondria. Toxicology Mechanisms and Methods. pp. 617-623.

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Abstract

Valproic acid (VPA), an anticonvulsant and mood-stabilizing drug, is widely used for the treatment of different types of seizures and myoclonic epilepsy. Several mechanisms have been suggested for VPA hepatotoxicity, and most of them are associated with oxidative stress. It seems that oxidative stress by VPA treatment has been associated with mitochondrial dysfunction. Therefore, this study investigated the mitochondrial toxicity mechanisms of VPA on freshly isolated rat mitochondria for better understanding pathogenesis of VPA in mitochondrial toxicity. Rat liver mitochondria were obtained by differential ultracentrifugation and were then incubated with different concentrations of VPA (25-200 mu M). Our results showed that VPA could induce oxidative stress via rising in mitochondrial reactive oxygen species formation, lipid peroxidation, mitochondrial membrane potential collapse, mitochondrial swelling and finally release of cytochrome c. These effects were well inhibited by pretreatment of isolated mitochondria with cyclosporin A and butylated hydroxytoluene. Based on these results, it is clear that VPA exerts mitochondrial toxicity by impairing mitochondrial functions leading to oxidative stress and cytochrome c expulsion, which start cell death signaling.

Item Type: Article
Keywords: Author Keywords:Cytochrome c; isolated mitochondria; mitochondrial membrane potential collapse (Delta Psi(m)); oxidative stress; valproic acid (VPA) KeyWords Plus:OXIDATIVE STRESS; INDUCED HEPATOTOXICITY; INDUCED APOPTOSIS; METABOLISM; CYTOTOXICITY; PEROXIDATION; HEPATOCYTES; MECHANISMS; PARAQUAT; INSIGHTS
Page Range: pp. 617-623
Journal or Publication Title: Toxicology Mechanisms and Methods
Abstract and Indexing: ISI, Pubmed, Scopus
Quartile : Q3
Volume: 23
Number: 8
Publisher: scopus
Depositing User: خانم مریم زرقانی
URI: http://repository.zums.ac.ir/id/eprint/1844

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