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  • Title: Melatonin attenuates unilateral ureteral obstruction-induced renal injury by reducing oxidative stress, iNOS, MAPK, and NF-kB expression.
    Author: Ozbek E, Ilbey YO, Ozbek M, Simsek A, Cekmen M, Somay A.
    Journal: J Endourol; 2009 Jul; 23(7):1165-73. PubMed ID: 19530942.
    Abstract:
    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-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.
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