Influence of ubiquinone on the inhibitory effect of adriamycin on mitochondrial oxidative phosphorylation.
The inhibition of succinate oxidation in both heart and liver mitochondria by the cardiotoxic anticancer antibiotic adriamycin in vitro was reversed to a large extent by exogenous ubiquinone-45. Inhibition of the oxidation of NAD+-linked substrates in heart and liver mitochondria responded differently to ubiquinone, the inhibition being reversed only in liver organelles. Administration of adriamycin inhibited oxidative phosphorylation in rat heart, kidney and liver mitochondria, the inhibition being highest in the heart organelles (about 50% for both NAD+-linked substrates and succinate). Exogenous addition of ubiquinone to mitochondria isolated from drug-treated animals did not reverse the inhibition. Administration of ubiquinone along with adriamycin did not change effectively the pattern of drug-mediated decrease in oxidative activity of the organelles, particularly in the heart.
D000818:Animals; D004317:Doxorubicin / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014451:Ubiquinone / Q000494:pharmacology*
D014451:Ubiquinone; D004317:Doxorubicin