Oxidative stress and apoptosis in cardiomyocyte induced by high-dose alcohol.

Binge drinking of alcohol causes cardiac dysfunction in some people. The mechanism remains unclear. This study was designed to investigate high doses of alcohol-induced oxidative stress and apoptosis in cardiomyocytes and protective effects of antioxidants. Cardiomyocytes isolated from 1- to 2-day-old Sprague-Dawley rats were treated with ethanol at doses of 0 mM, 50 mM, 100 mM, and 200 mM for 24 hours. Vitamin E (1 mM) and vitamin C (0.2 mM) were added to medium 1 hour before addition of ethanol. Results showed typical apoptosis: chromatin condensation, membrane blebbing, shrinkage, and cytoplasm condensation. Apoptosis is concentration-dependent in the range of 0 to 100 mM ethanol (apoptosis rates were respectively 0.68%, 2.03%, and 9.66% at ethanol concentration of 0 mM, 50 mM, and 100 mM). Necrotic cells became greatly increased in the 200 mM ethanol-treated group. Intracellular production of reactive oxygen intermediates increased as mitochondrial membrane potential decreased after ethanol treatment. Cytochrome c was found to be greater in the cytosol of the ethanol-treated groups. Activity of caspase-3 was higher in ethanol-treated groups (P < 0.05). Both vitamin E and vitamin C inhibited oxidative stress and myocyte apoptosis in ethanol-treated groups (P < 0.05). In conclusion, our data indicated that acute high-dose ethanol treatment primarily induces cardiomyocyte apoptosis at concentration up to 100 mM while necrosis is predominate at 200 mM. The underlying mechanism appears to involve mitochondrial damage via an increase in oxidative stress and releasing cytochrome c, which activates caspases that initiate chromatin fragmentation and apoptosis. Antioxidants, to a large extent, inhibit oxidative stress and apoptosis induced by ethanol.