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 the mitochondrial electron transport chain in cultures of neonatal rat cardiomyocytes and in isolated myocardial mitochondria. Cocaine concentrations (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). Reduction of tetrazolium compounds, neotetrazolium chloride (NTC) and triphenyltetrazolium chloride (TTC) was analyzed in intact cells to assess activity of the mitochondrial electron transport chain. 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.
Yuan
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C
University of Cincinnati Medical Center, College of Pharmacy, OH 45267-0004, USA.
Acosta
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D
D000818:Animals; D000831:Animals, Newborn; D002458:Cell Fractionation; D002478:Cells, Cultured; D003042:Cocaine / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts / Q000378:metabolism
D013778:Tetrazolium Salts; D007770:L-Lactate Dehydrogenase; D003042:Cocaine