Relation between cardiotoxic effect of adriamycin and superoxide anion radical.
The investigation was undertaken to study a possible mechanism for adriamycin cardiotoxicity. The activities of superoxide dismutase and catalase in the heart of mice were increased significantly by the intraperitoneal administration of 15 mg/kg of adriamycin. In contrast, these enzymes in the liver and kidney were unaffected by this dose of adriamycin. In vitro studies revealed that adriamycin inhibited the NADH-cytochrome c oxidoreductase activity of mitochondria in the guinea pigs heart. Moreover adriamycin stimulated the formation of superoxide anion radical in mitochondria isolated from guinea pigs. Particularly, the formation of superoxide anion radical in the heart mitochondria was 5 times higher than that in the liver mitochondria particle. On the other hand, the contents of superoxide dismutase in the heart were significantly lower than that in the liver. These results suggest that the cardiotoxic effect of adriamycin is caused by the following mechanism: adriamycin directly stimulates the formation of superoxide anion radical, particularly in the heart mitochondria. In spite of the induction of defence enzymes such as superoxide dismutase and catalase, their abilities seem to be swamped by enhanced active oxygen radicals.
D000818:Animals; D002374:Catalase / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity*; D005609:Free Radicals; D006168:Guinea Pigs; D006331:Heart Diseases / Q000139:chemically induced*; D050356:Lipid Metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D051379:Mice; D008930:Mitochondria, Liver / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D005609:Free Radicals; D008054:Lipid Peroxides; D013481:Superoxides; D004317:Doxorubicin; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen