Melatonin, a pineal hormone with antioxidant property, protects against gentamicin-induced nephrotoxicity in rats

The present study investigated the effects of melatonin, an antioxidant, on gentamicin-induced nephrotoxicity in rats. Melatonin (5 mg/kg p.o.) was us ed 3 days before and 8 days simultaneously with gentamicin (80 mg/kg i.p.) Saline-treated animals served as controls. Determinations of urinary creati nine, N-acetyl-beta-D-glucosaminidase, glucose, protein, blood urea, serum creatinine, plasma and kidney tissue malondialdehyde (MDA), and antioxidant enzyme levels in kidney tissue were done after 8 days of gentamicin treatm ent. The kidneys were also examined for morphological changes using histolo gical techniques. Gentamicin caused nephrotoxicity as evidenced by marked e levation in blood urea and serum creatinine. Mean blood urea and serum crea tinine levels were 289 +/- 50, and 2.5 +/- 0.5 mg/dl, respectively, in rats treated with gentamicin. Melatonin significantly protected the rats from g entamicin-induced nephrotoxicity; blood urea and serum creatinine levels we re 23 +/- 2.7 and 0.88 +/- 0.19 mg/dl, respectively. The creatinine clearan ce was decreased with gentamicin treatment (0.048 +/- 0.007 ml/min) as comp ared with controls (0.41 +/- 0.08 ml/h/kg). In rats treated with melatonin plus gentamicin, the creatinine clearance was similar to controls (0.41 +/- 0.08 ml/h/kg). The product of lipid peroxidation (MDA) was markedly increa sed in plasma (2.10 +/- 0.15 nmol) and kidney tissue (8.87 +/- 3.2 nmol/mg protein) with gentamicin treatment. Melatonin prevented the gentamicin-indu ced rise in plasma MDA (1.03 +/- 0.27 nmol) and kidney tissue MDA (2.57 +/- 0.87 nmol/mg protein). An increased excretion of urinary N-acetyl-beta-D-g lucosaminidase, glucose, and protein by gentamicin was also prevented by me latonin. Kidneys from gentamicin-treated rats showed tubular epithelial los s with intense granular degeneration involving more than 50% of renal corte x, while there were findings comparable to controls in melatonin plus genta micin treated rats. The present study indicates that melatonin significantl y protects against gentamicin-induced renal toxicity in Wistar rats. Copyri ght (C) 2000 S. Karger AG, Basel.