POTENTIATION OF COCAINE HEPATOTOXICITY IN HUMAN HEPATOCYTES BY ETHANOL

The cytotoxic effect of cocaine on human hepatocytes was evaluated aft er 24 hr of exposure to cocaine by measuring the leakage of intracellu lar lactate dehydrogenase and the reduction of MTT. According to these endpoint parameters, the half-maximal cytotoxic concentration (IC50) of cocaine was 6.8 and 7.8 mM, respectively. Lower concentrations of c ocaine, however, impaired basic metabolic functions of human hepatocyt es. Exposure of cells to 2 mM-cocaine resulted in a 50% decrease in he patic glycogen, a 40% decrease in cellular glutathione content and a 4 0% decrease in urea synthesis with respect to control values. Ethanol greatly potentiated cocaine-induced hepatotoxicity. After a 48-hr pret reatment of human hepatocytes with 50 mM-ethanol, concentrations of co caine (0.25 mM) that had no effects on hepatocyte metabolism in the ab sence of ethanol, caused a 20% inhibition of the urea synthesis rate, a 40% depletion of glycogen stores and a 30% reduction in glutathione content. The results of our work show that ethanol significantly incre ases the toxic effects of cocaine on human hepatocytes.