Protective effect of melatonin against adriamycin toxicity in the rat.
Adriamycin, an anthracyclinic antibiotic frequently used in quimioterapeutic treatments is highly toxic; it inhibits protein synthesis and provokes prooxidant effects. Melatonin has recently been shown to have high antioxidative 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 microg/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/GSSG) 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 pharmacological doses of melatonin, the decrease in the GSH/GSSG ratio was significantly reduced but the reduction in GPx activity was not attenuated. A significant 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 melatonin. Our results demonstrate that oxidative damage induced by the antitumor drug, adriamycin, can be reduced by low pharmacological doses of melatonin.
Agapito
M T
MT
Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Valladolid, Spain. teresaa@bio.uva.es
Antolín
Y
Y
del Brio
M T
MT
López-Burillo
S
S
Pablos
M I
MI
Recio
J M
JM
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology; D004317:Doxorubicin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D008315:Malondialdehyde; D004317:Doxorubicin; D005979:Glutathione Peroxidase; D005978:Glutathione; D008550:Melatonin; D019803:Glutathione Disulfide