Effect of cocaine on mitochondrial electron transport chain evaluated in primary cultures of neonatal rat myocardial cells and in isolated mitochondrial preparations

Cardiotoxicity is commonly associated with cocaine abuse. Previous studies have indicated that cocaine alters myocardial mitochondrial function. This study was undertaken to investigate the effect of cocaine on activity of th e mitochondrial electron transport chain in cultures of neonatal rat cardio myocytes and in isolated myocardial mitochondria. Cocaine concentrations (1 0(-5) to 10(-3) M) were used, and these concentrations have been reported i n human cocaine users and are within a similar range of cocaine concentrati ons used in studies in vivo. After 24 hr treatment of cocaine, there was a slight increase in lactate dehydrogenase leakage in the cells treated with cocaine (10(-3) M). Reduction of tetrazolium compounds, neotetrazolium chlo ride (NTC) and triphenyltetrazolium chloride (TTC) was analyzed in intact c ells to assess activity of the mitochondrial electron transport chain. Coca ine (10(-3) M) did not significantly change TTC and NTC reduction. In isola ted mitochondria, cocaine (10(-3) M) significantly inhibited glutamate/mala te-mediated respiration. These data suggest that cocaine at high concentrat ions may inhibit complex I of the mitochondrial electron transport chain of myocardial cells.