Comparison of the efficacy of melatonin and 1400W on renal ischemia/reperfusion injury: a role for inhibiting iNOS.

Introduction: We investigated the roles of melatonin (a powerful antioxidant, iNOS inhibitor, and a scavenger of peroxynitrite) and 1400W (a strong and selective inhibitor of inducible nitric oxide) on renal dysfunction and injury induced by ischemia/reperfusion (I/R) of rat kidney, since oxidative and nitrosative injury are believed to be the major causes.

Materials And Methods: Thirty-two male Sprague-Dawley rats were divided into four groups of sham-operated, I/R, I/R + Melatonin and I/R + 1400W. Rats were given either melatonin (10 mg/kg) or 1400W (10 mg/kg) in the I/R + Melatonin and I/R + 1400W groups respectively at 6 h prior to ischemia and at the beginning of reperfusion via intraperitoneal route. I/R injury was induced by 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood were obtained for histopathologic and biochemical evaluation.

Results: Melatonin and 1400W had an ameliorative effect on both oxidative and nitrosative stress in the kidneys against renal I/R injury in rats. In addition, melatonin significantly reduced elevated nitro-oxidative stress product, restored decreased antioxidant enzymes and attenuated histological alterations when compared with 1400W.

Conclusions: Both Melatonin and 1400W were efficient in ameliorating experimental I/R injury of the kidneys. Moreover, melatonin was more effective than 1400W possibly through inhibiting iNOS as well as scavenging free oxygen radicals and peroxynitrite.