MITOCHONDRIAL SENSITIVITY TO AZT

The possibility of tissue-specific effects regarding mitochondrial sen sitivity to AZT was evaluated in this study. When mitochondria isolate d from liver, kidney, skeletal and cardiac muscle were oxidizing gluta mate, a dose-dependent inhibition by AZT of state 3 respiration was ob served; using succinate as substrate the inhibition occurred only in s keletal and cardiac muscle mitochondria. The same results were obtaine d with FCCP-uncoupled mitochondria. NADH oxidase of intact and disrupt ed mitochondria, isolated from all four tissues was strongly inhibited . Succinate oxidase activity was inhibited by AZT only in intact mitoc hondria from skeletal and cardiac muscles, suggesting the involvement of succinate transport systems. Similarly, inhibition by the drug of t he hydrolytic activity of Hf-ATPase was observed only in mitochondria of these tissues. These effects taken together, indicate a tissue/carr ier-specific inhibition in vitro, although its precise mechanism requi res further research. (C) 1998 John Wiley & Sons, Ltd.