Melatonin Attenuates Unilateral Ureteral Obstruction-Induced Renal Injury by Reducing Oxidative Stress, iNOS, MAPK, and NF-κB Expression

Purpose: To investigate whether melatonin (MLT) treatment has any protective effect on unilateral ureteral obstruction (UUO)-induced kidney injury in rats. Materials and 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-kappa B) 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-kappa B expression. MLT treatment resulted in reduction of the parameters of oxidative stress and the iNOS, p38-MAPK, and NF-kappa B 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-kappa B, since MLT reduces the activation of these pathways.