Mitochondrial impairment contributes to cocaine-induced cardiac dysfunction: Prevention by the targeted antioxidant MitoQ

作者：Vergeade Aurelia; Mulder Paul; Vendeville Dehaudt Cathy; Estour Francois; Fortin Dominique; Ventura Clapier Renee; Thuillez Christian; Monteil Christelle^*

来源：Free Radical Biology and Medicine, 2010, 49(5): 748-756.

DOI：10.1016/j.freeradbiomed.2010.05.024

• Heart
• Cocaine
• Cardiac dysfunction
• Reactive oxygen species
• Mitochondria
• Interfibrillar mitochondria
• MitoQ
• Free radicals

The goal of this study was to assess mitochondrial function and ROS production in an experimental model of cocaine-induced cardiac dysfunction We hypothesized that cocaine abuse may lead to altered mitochondrial function that in turn may cause left ventricular dysfunction Seven days of cocaine administration to rats led to an increased oxygen consumption detected in cardiac fibers, specifically through complex I and complex III ROS levels were increased, specifically in interfibrillar mitochondria In parallel there was a decrease in ATP synthesis, whereas no difference was observed in subsarcolemmal mitochondria This uncoupling effect on oxidative phosphorylation was not detectable after short-term exposure to cocaine, suggesting that these mitochondrial abnormalities were a late rather than a primary event in the pathological response to cocaine MitoQ, a mitochondrial-targeted antioxidant, was shown to completely prevent these mitochondrial abnormalities as well as cardiac dysfunction characterized here by a diastolic dysfunction studied with a conductance catheter to obtain pressure-v

• 出版日期2010-9-1