Effect of alpha-lipoic acid on oxidative stress status in rat kidney subjected to ischemia/reperfusion injury

ABSTRACT

Renal ischemia/reperfusion [I/R] injury is a major cause of acute renal failure in both native kidneys and renal allografts. There is increasing evidence to suggest that reactive oxygen species [ROS] play a role in the pathogenesis of I/R injury in the kidney. This study was designed to investigate the effect of alpha-lipoic acid [LA] on the alterations of oxidative stress status in rat kidney subjected to I/R injury. Wistar albino rats were allocated into Three groups; [1] sham operated control; [2] I/R group in which ischemia was induced by a right renal pedicle occlusion for 30 min followed by 10 min of reperfusion with contralateral nephrectomy; [3] LA + I/R group in which animals were pretreated with LA [100 mg/kg i.p.] for 7 days before I/R insult. At the end of the reperfusion period, animals were sacrificed. Kidneys were isolated for histological examination or determination of the renal malondialdehyde [MDA], glutathione [GSH], glutathione peroxidase [GPx] and glutathione reductase [GR] levels/activities as oxidative stress markers. Kidney myeloperoxidase [MPO] activity and nitrite/nitrate [NO[x] content were assessed as indices of neutrophil infiltration and nitric oxide metabolism respectively. In addition renal lactate content, serum urea and creatinine levels were also measured. I/R injury caused marked increases in renal MDA level, lactate content and MPO activity, associated with significant decreases in GSH level, GPx and GR activities as well as NO[x] content. This biochemical derangement was accompanied by severe histological lesions. Pretreatment with LA significantly reduced the enhanced oxidative stress, neutrophil infiltration and increased lactate content in the ischemic rat kidney. It also improved the histological alterations induced by renal I/R injury. So, It could be concluded that LA pretreatment effectively improved the antioxidant/oxidant imbalance associated with renal I/R injury in rats