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Showing results for tags 'zoloft mitochondria damage'.
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Toxicol. Sci. (2012) 127 (2): 582-591. doi: 10.1093/toxsci/kfs100 First published online: March 2, 2012 Mitochondrial Dysfunction Induced by Sertraline, an Antidepressant Agent Yan Li*, Letha Couch†, Masahiro Higuchi‡, Jia-Long Fang† and Lei Guo†,1 Abstract and full free text at http://toxsci.oxfordjournals.org/content/127/2/582.short Sertraline, a selective serotonin reuptake inhibitor, has been used for the treatment of depression. Although it is generally considered safe, cases of sertraline-associated liver injury have been documented; however, the possible mechanism of sertraline-associated hepatotoxicity is entirely unknown. Here, we report that mitochondrial impairment may play an important role in liver injury induced by sertraline. In mitochondria isolated from rat liver, sertraline uncoupled mitochondrial oxidative phosphorylation and inhibited the activities of oxidative phosphorylation complexes I and V. Additionally, sertraline induced Ca2+-mediated mitochondrial permeability transition (MPT), and the induction was prevented by bongkrekic acid (BA), a specific MPT inhibitor targeting adenine nucleotide translocator (ANT), implying that the MPT induction is mediated by ANT. In freshly isolated rat primary hepatocytes, sertraline rapidly depleted cellular adenosine triphosphate (ATP) and subsequently induced lactate dehydrogenase leakage; both were attenuated by BA. Our results, including ATP depletion, induction of MPT, inhibition of mitochondrial respiration complexes, and uncoupling oxidative phosphorylation, indicate that sertraline-associated liver toxicity is possibly via mitochondrial dysfunction. http://toxsci.oxfordjournals.org/content/127/2/582.short
