EFFECT OF COCAINE ON MITOCHONDRIAL ELECTRON TRANSPORT CHAIN EVALUATED INPRIMAPY CULTURES OF NEONATAL RAT MYOCARDIAL CELLS AND IN ISOLATED MITOCHONDRIAL PREPARATIONS

摘要

Cardiotoxicityis commonly is commonly associated with cocaine abuse. Previous studies have indicated that cocaine alters myocardial mitochondrial functin. This study was undertaken to investigate the effect of cocaine on activity of the mitochondrial electron transport chain in cultures of neonatal rat cardiomyocytes and in isolated myocardial mitochondria. Cocaine concntrations (10~(-5) to 10~(-3)M)were used, and these concentrations have been reported in human cocaine users and are within a similar range of cocaine concentrations 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).Reductin of tetrazolium compounds, neotetrazolium chloride (NTC)and triphenyltetrazolium chloride (TTC)was analyzed in intact cells to assess activity of the mitochondrial electron transport cahin. Cocaine (10~(-3)M) did not significantly change TTC and NTC reduction. In isolated mitochondria, cocaine (10~(-3)M)significantly inhibited glutamate/malate-mediated respiration. These data suggest that cocaine at high concentrations may inhibit complex I of the mitochondrial electron transport chain of myocardial cells.