RHEIN ENHANCES THE EFFECT OF ADRIAMYCIN ON MITOCHONDRIAL RESPIRATION BY INCREASING ANTIBIOTIC-MEMBRANE INTERACTION

The effect of the combination of Adriamycin (ADM) with rhein (RH), an anti-inflammatory drug, on the electron flow through site III and IV o f the respiratory chain of rat liver mitochondria was investigated. RH , even at high concentrations, does not inhibit either duroquinol (DHQ ) oxidation or cytochrome oxidase activity bath of which are decreased by ADM in a dose-dependent manner. The analysis of interaction, perfo rmed with the isobolar method, shows a strong synergistic effect that cannot be ascribed to increased permeability of the mitochondrial memb ranes brought about by RH. The mechanism by which RH potentiates the e ffect of ADM on DHQ oxidation and cytochrome oxidase activity is most likely to be changes induced in the physical status of the inner mitoc hondrial membrane such as to permit low ADM concentrations to bind and segregate enough cardiolipin to inhibit electron transport through co mplex III and IV.