Melatonin attenuates unilateral ureteral obstruction-induced renal injury by reducing oxidative stress, iNOS, MAPK, and NF-kB expression.
OBJECTIVE
To investigate whether melatonin (MLT) treatment has any protective effect on unilateral ureteral obstruction (UUO)-induced kidney injury in rats.


METHODS
Six animals were included in each of the following five groups: group 1, sham operation but no treatment; group 2, unilateral ureteral ligation but no treatment; group 3, sham operation + MLT; group 4, unilateral ureteral ligation + MLT; group 5, unilateral ureteral ligation +5% ethanol (the vehicle of MLT). The injected dose of MLT was 1 mg/kg/day (intraperitoneal). MLT and vehicle were injected daily, beginning 5 days before the unilateral ureteral ligation or sham operation and until 10 days after it. At 10 days after UUO, all rats were sacrificed with high-dose ketamine. Malondialdehyde, glutathione, nitric oxide (NO), and 8-hydroxydeoxyguanosine levels and inducible NO synthase (iNOS), p38-mitogen-activated protein kinase (p38-MAPK), and nuclear factor kappa B (NF-kB) expression were studied. Histopathological examination of the obstructed kidney was also performed.


RESULTS
UUO was accompanied by a significant increase in malondialdehyde, NO, and 8-hydroxydeoxyguanosine along with a significant decrease in glutathione levels in the kidney tissue, as well as a significant elevation in iNOS, p38-MAPK, and NF-kB expression. MLT treatment resulted in reduction of the parameters of oxidative stress and the iNOS, p38-MAPK, and NF-kB expression. MLT treatment also reduced the development of leukocyte infiltration and interstitial fibrosis in UUO rats.


CONCLUSIONS
MLT may prevent UUO-induced kidney damage in rats by reducing oxidative stress. The mechanism for this is likely mediated via reduction in the expression of iNOS, p38-MAPK, and NF-kB, since MLT reduces the activation of these pathways.
Ozbek
Emin
E
Department of Urology, Bezm-i Alem Valide Sultan Vakif Gureba Research and Education Hospital, Istanbul, Turkey.
Ilbey
Yusuf Ozlem
YO
Ozbek
Mustafa
M
Simsek
Abdulmuttalip
A
Cekmen
Mustafa
M
Somay
Adnan
A
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D005355:Fibrosis / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014517:Ureteral Obstruction / Q000150:complications* / Q000201:enzymology
D016328:NF-kappa B; D009569:Nitric Oxide; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione; D008550:Melatonin