The protective effect of melatonin on cisplatin nephrotoxicity

Regarding the mechanisms of cisplatin (CP) nephrotoxicity, several hypothes es have been put forward, among which oxidative stress (including depiction of glutathione and production of lipid peroxide) is noticeable. This inves tigation elucidates the role of the antioxidant system in CP-induced nephro toxieity and the nc phroprotection by melatonin. Balb/c mice were injected i.p. with: 1) vehicle control; 2) a single dose of 6.5 mg/kg cisplatin, CP group; 3) melatonin in a dose of 10 mg/kg for 5 days after CP injection, CP -M group; 4) melatonin (10 mg/kg) for 5 days before and after CP injection, M-CP-M group; 5) melatonin in a dose of 10 mg:kg For 5 days, M group. Mice were sacrificed 5 days after CP injection to determine blood urea nitrogen (BUN) and serum creatinine, Renal lipid peroxidation (LF) and glutathione (GSH) levels were evaluated in kidney homogenates. Cisplatin administration resulted in increased LP, BUN and serum creatinine levels and decreased GS H levels, whereas melatonin reversed these effects. Morphological kidney da mage was apparent in the CP group. Mentioned degeneration was moderate in t he CP-M group, whereas morphological findings of the M-CP-M group implied a well preserved kidney tissue. When M was administered alone, it didn't cau se any significant change in biochemical parameters. Both C and M groups ex hibited similar biochemical and morphological findings in light and transmi ssion electron microscope observation. In conclusion, the present study sug gests that melatonin may be of therapeutic benefit when used with CP. (C) 2 000 Editions scientifiques et medicales Elsevier SAS.