Melatonin administration prevents the nephrotoxicity induced by gentamicin.

Abstract

To investigate the effect of melatonin on the antioxidant enzyme activity and renal tubular necrosis induced by gentamicin. Twenty-four adult male Sprague-Dawley rats were divided into three equal groups. In group 1, the rats were injected with vehicle (controls), in group 2 they were injected with gentamicin for 5 days and in group 3 injected with gentamicin plus melatonin for 5 days. At 24 h after the last injection, rats were killed and the renal cortex separated from the medulla. Most of the cortex was homogenized but a small sample was fixed in formaldehyde solution for histological examination by light microscopy. Blood samples were also taken to assess the serum levels of urea, creatinine, Na+, K+ and gamma-glutamyl transpeptidase (gamma-GT); before death, urine samples were analysed for protein content. Crude extracts of the cortex were used to determine lipoperoxides, reduced glutathione (GSH-Px), catalase and superoxide dismutase (SOD). The results were compared using the Mann-Whitney U-test. Compared with the controls rats, gentamicin caused hyperproteinuria, an increase in the level of gamma-GT in serum, a marked increase in lipoperoxides and a significant decrease of GSH-Px, catalase and SOD activity in the kidney. In the rats in group 3 there was a marked restoration in lipid peroxidation, GSH-Px, catalase, SOD activity and proteinuria, and in gamma-GT in serum. In rats in group 2 there was widespread tubular necrosis (grade 2-4) but in rats in group 3 there was a marked reduction in the extent of tubular damage. There was no significant difference in serum levels of Na+, K+, blood urea nitrogen and creatinine. These results indicate that melatonin prevents the tubular necrosis induced by gentamicin in rats, presumably because it is a potent antioxidant and restores antioxidant enzyme activity in the rat kidney.