Abstract 444: Differential Contribution of Oxygenases in Glycerol-Induced Acute Renal Failure in the Rats

Abstract

Oxidative stress has long been identified as one if the mechanism in glycerol-induced acute renal failure (ARF), a disease model of human rhabdomyolysis. Besides NAD(P)H Oxidase, cyclooxygenase (COX) and xanthine oxidase (XO) are important oxygenase system that contributes in free radical generation in the biological system. In this study we explore involvement of these oxygenase system as the source of free radical in ARF and investigate the relationship between NAD(P)H oxidase, COX and XO in this process. Renal failure was induced in male Sprague Dawley rats by injecting glycerol (8 ml / kg; 50% v/v; i.m) with or without pretreatment of apocynin (Apo: mg/kg in drinking water, 7 days) a NAD(P)H Oxidase inhibitor. Rats were sacrificed 24 hrs after inducing ARF and kidney tissues were analyzed for biochemical assays. Glycerol increased free radical production by 39% as evident by elevated 8-isoprostane. Inhibition of NAD(P)H oxidase by apocynin reduced free radicals by 46%. In ARF rats, NAD(P)H oxidase, COX and XO activities were elevated by 106%, 70%, and 208%, respectively. Apocynin prevented this attenuation of NAD(P)H oxidase (54%; p<0.05) and COX (62%; p<0.05) but did not alter XO activity. These data suggests that NAD(P)H oxidase, COX, and XO are involved in generating oxidative stress in ARF. We also propose that COX-mediated free radical generation requires a functional NAD(P)H oxidase.