Anthracycline-Enhanced Cardiac Oxygen Radical Metabolism
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The anthracycline quinones play an important role in the chemotherapeutic management of a wide variety of human malignancies including acute myelogenous and lymphocytic leukemias, the non-Hodgkin’s lymphomas, and carcinomas of the breast, lung, and thyroid (1). The clinical usefulness of these drugs may be limited, however, by the development of a dose-related, congestive cardiomyopathy that is sometimes fatal (2). There is currently a substantial body of experimental data supporting the hypothesis that the myocardial injury produced by anthracycline antibiotics is related to drug-induced reactive oxygen production in the heart (3–6). These investigations include studies which show that the morphologic expression of doxorubicin cardiac toxicity may be enhanced by inhibition of cardiac antioxidant defense systems; that damage to the heart may be reduced or abolished by pretreatment of experimental animals with various free radical scavengers; and that cyclical reduction and oxidation of the doxorubicin quinone leads to the depletion of critical cardiac energy stores, as well as to the inability of intact myocytes to maintain calcium homeostasis (7–10).
KeywordsRedox Cycling Hydroxyl Radical Production Hydroxyl Radical Formation Superoxide Anion Formation Anthracycline Antibiotic
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