Melatonin administration prevents the nephrotoxicity induced by gentamicin.
OBJECTIVE
To investigate the effect of melatonin on the antioxidant enzyme activity and renal tubular necrosis induced by gentamicin.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Ozbek
E
E
Departments of Urology, Biochemistry, Pharmacology and Pathology, Inonu University School of Medicine, Malatya, Turkey. eozbek@superonline.com
Turkoz
Y
Y
Sahna
E
E
Ozugurlu
F
F
Mizrak
B
B
Ozbek
M
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000032:analysis; D005839:Gentamicins / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D005978:Glutathione / Q000032:analysis; D007684:Kidney Tubules / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D011507:Proteinuria; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013482:Superoxide Dismutase / Q000032:analysis; D005723:gamma-Glutamyltransferase / Q000097:blood
D000975:Antioxidants; D005839:Gentamicins; D002374:Catalase; D013482:Superoxide Dismutase; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D008550:Melatonin