NADPH oxidase inhibition prevents cocaine-induced up-regulation of xanthine oxidoreductase and cardiac dysfunction
- 作者：Marc Isabelle ; Auré ; lia Vergeade ; Fabienne Moritz ; Brigitte Dautré ; aux ; Jean-Paul Henry ; Franç ; oise Lallem ; Vincent Richard ; Paul Mulder ; Christian Thuillez ; Christelle Monteil
- 关键词：Cocaine ; Oxidative stress ; NADPH oxidase ; Xanthine oxidase ; Cardiac function ; Reactive oxygen species
- 刊名：Journal of Molecular and Cellular Cardiology
- 出版年：2007
- 期刊代码：171_00222828
- 类别：bio
- 出版时间：February 2007
- 卷：42
- 期：2
- 页码：326-332
- 文件大小：546 K
摘要
Oxidative stress is involved in the pathogenesis of cocaine-induced cardiomyopathy. In the present study, we aimed to determine the enzymatic sources of reactive oxygen species (ROS) production, namely NADPH oxidase and xanthine oxidoreductase (XOR) in male Wistar rats treated for 7 days with cocaine (2 × 7.5 mg/kg/day, ip) or cocaine with a NADPH oxidase inhibitor (apocynin, 50 mg/kg/day, po) or a XOR inhibitor (allopurinol, 50 mg/kg/day, po). Cocaine-induced cardiac dysfunction is associated with an increase in NADPH oxidase and XOR activities (59%and 29%, respectively) and a decrease in catalase activity. Apocynin or allopurinol treatment prevents the cocaine-induced cardiac alteration by restoration of cardiac output, stroke volume and fractional shortening. This is associated with a reduction of the myocardial production of superoxide anions and an enhancement of catalase activity. Surprisingly, apocynin treatment prevents XOR up-regulation supporting the hypothesis that NADPH oxidase-derived ROS play a role in modulating ROS production by XOR. These data suggest that NADPH and xanthine oxidase act synergically to form myocardial ROS and clearly demonstrate that their inhibition may be critical in preventing the initiation and progression of cocaine-induced LV dysfunction.