Protective effect of melatonin against adriamycin toxicity in the rat

Adriamycin, an anthracyclinic antibiotic frequently used in quimioterapeuti c treatments is highly toxic: it inhibits protein synthesis and provokes pr ooxidant effects. Melatonin has recently been shown to have high antioxidat ive properties. We tested if melatonin is able to neutralize the oxidative damage induced by a single dose (20 mg/kg, i.p.) of adriamycin preceded (3 days) and followed (7 days) by a low pharmacological dose (50 mug/kg, i.p.) of melatonin. After the administration of a single dose of adriamycin (20 mg/kg i.p.) to male Wistar rats, the reduced to oxidized glutathione (GSH/G SSG) ratio and the glutathione peroxidase (GPx, E.C. 1.11.1.9.) activity in the brain, intestine. heart, kidney. and lung were significantly reduced. When the treatment of adriamycin was preceded and followed by low pharmacol ogical doses of melatonin, the decrease in the GSH/GSSG ratio was significa ntly reduced but the reduction in GPx activity was not attenuated. A signif icant increase in lipid peroxidation products was observed in brain. heart, and kidney tissues after a single administration of adriamycin, which was attenuated by pre- and post-treatment with a low pharmacological dose of me latonin. Our results demonstrate that oxidative damage induced by the antit umor drug, adriamycin, can be reduced by low pharmacological doses of melat onin.