Research Funding

This is a comment on the excellent review by Olson and Mushlin (1) on “Doxorubicin cardiotoxicity: analysis of prevailing hypotheses?’ We wish to draw attention to another interesting effect of adriamycin (doxorubicin), specific for heart-tissue mitochondria. We reported in 1982 (2, 3) that this antitumor antibiotic inhibited oxidative phosphorylation (manometric assay) in freshly prepared mitochondria from heart, liver, and kidney, with the succinate-dependent activity in heart mitochondria being extremely sensitive to the drug. To obtain 50% inhibition of rates of oxidation and phosphorylation in intact rat-heart mitochondria, only 5.5 itM adriamycin is needed when succinate is the substrate, compared with a requirement for concentrations two orders of magnitude higher for other test systems. This selective inhibition needs intact heart mitochondria and succinate substrate and is potentiated by hexokinase present in the manometric assay. A component between the succinate dehydrogenase flavoprotein and ubiquinone in the respiratory chain appears to be the sensitive site.