Effect of ketoconazole on bioenergetic functions of isolated rat liver mitochondria

Abstract

The study investigates the effects of ketoconazole on the bioenergetic functions of isolated rat liver mitochondria. Ketoconazole decreased rate of state 3 and 3u respiration with NAD+- link substrate (glutamate, [alpha]-ketoglutarate, [beta]-hydroxybutyric acid, pyruvate) probably by inhibit complex I of the respiratory chain leading to lessen oxidative phosphorylation and ATP synthesis. The inhibitory effect of ketoconazole probable declined when the incubation medium pH was acidic, but not significantly. Bovine serum albumin attenuated the action of ketoconazole. Dithiothreitol could not influence inhibition of ketoconazole. No any effect on ATPase activity while ketoconazole could suppress MAO activity. And express inhibitory effect on calcium stimulated respiration. It remains to be determined whether these mitochondrial effects of ketoconazole contribute to the pharmacological and/or toxicological action of this drug.