MELATONIN, A PINEAL HORMONE WITH ANTIOXIDANT PROPERTY, PROTECTS AGAINST ADRIAMYCIN CARDIOMYOPATHY IN RATS

Adriamycin (ADR) is a potent, broad-spectrum chemotherapeutic agent wh ose clinical use is limited by its cardiotoxicity. Since the pathogene sis of ADR-induced cardiomyopathy may involve free radicals and lipid peroxidation, the antioxidant, melatonin (MEL) may protect against tox ic effects of ADR. We therefore tested this hypothesis using a rat mod el of ADR-induced cardiomyopathy. Sprague Dawley rats were given ADR ( cumulative dose, 15 mg/kg), MEL (cumulative dose, 84 mg/kg), ADR+MEL, ADR plus probucol (PRB, cumulative dose, 90 mg/kg), or vehicle alone, according to known regimens. The rats were maintained for 3 weeks foll owing treatment, after which their cardiac performance was measured. F ollowing sacrifice, their myocardial ultrastructure was examined, and their myocardial lipid peroxidation was assessed. Mortality was observ ed only in rats treated with ADR alone. When compared to control rats, surviving rats in the ADR group showed significant decreases in ratio of heart to body weight, arterial pressure, and left ventricular frac tional shortening as well as a significant accumulation of ascites. Th e amount of myocardial thiobarbituric acid reactive substances was sig nificantly higher in ADR-treated than in control rats. Both antioxidan ts, MEL and PRB, significantly prevented these ADR-induced changes. El ectron microscopic examination revealed myocardial lesions indicative or ADR-induced cardiomyopathy in the ADR-treated mts. In contrast, tre atment of these rats with MEL or PRE preserved myocardial ultrastructu re. By preventing lipid peroxidation, MEL may be highly effective in p rotecting against ADR-induced cardiomyopathy.