Melatonin and oxidative damage in mice liver induced by the prooxidant antitumor drug, Adriamycin

Antioxidant properties have been attributed to melatonin; it seemed therefore worthwhile to determine its effects in relation to the prooxidant action of adriamycin, which contributes to its toxic and therapeutic effects. Melatonin effectively acts as a direct free radical scavenger in the concentration range of 20-100 microM as determined in vitro, using Fenton reaction as a source of free radicals that were determined by EPR using spin trapping method. Following the administration of a single i.v. dose of 28 mg/Kg or of 3 repeated i. p. doses of 5 mg/Kg adriamycin to CBA mice, glutathione levels in the liver cells were significantly reduced. When the treatment with adriamycin was preceded by the s.c. administration of 2 mg/Kg melatonin, the decrease in total and reduced glutathione concentrations was significantly prevented. A significant increase in lipid peroxidation was observed in liver cells after a single administration of adriamycin which was not attenuated by pretreatment with melatonin. These results indicate that further examination of the possible protective action of melatonin on the toxic effects of prooxidant antitumor drugs on normal and neoplastic tissues would be of interest also in relation to their chronotoxicological properties.