Effects of bezafibrate on the bioenergetic functions of isolated rat liver mitochondria

Abstract

The present study investigates the effects of bezafibrate on the main bioenergetic functions of isolated rat liver mitochondria. Bezafibrate decreased rates of states 3 and 3u respiration with glutamate plus malate as substrates probably by inhibiting complex I of the respiratory chain leading to diminished oxidative phosphorylation and ATP synthesis. The inhibitory effect of bezafibrate increased when the incubation medium pH was acidic while bovine serum albumin attenuated the action of the drug. Dithiothreitol and Mg2+ did not significantly influence bezafibrate action. Bezafibrate slightly inhibited the uncoupler-induced ATPase activity. The investigation using calcium-selective electrode showed that bezafibrate has small inhibitory effect on mitochondrial calcium uptake but clearly exhibited the calcium-releasing effect. Mitochondrial monoamine oxidase activity was unaffected by bezafibrate. It remains to be determined whether these mitochondrial effects of bezafibrate contribute to the pharmacological and / or toxicological actions of this hypolipidemic drug.