Beneficial effects of N-acetylcysteine and ebselen on renal ischemia/reperfusion injury

Ren Fail. 2011;33(5):512-7. doi: 10.3109/0886022X.2011.574767. Epub 2011 May 6.

Abstract

Introduction: It has been demonstrated that peroxynitrite accompanies acute renal ischemia and contributes to the pathophysiology of renal damage. Therefore, we aimed to investigate the roles of N-acetylcysteine (NAC), a well-known powerful antioxidant, and ebselen (E), a scavenger of peroxynitrite, on renal injury induced by renal ischemia/reperfusion injury (IRI) of rat kidney.

Materials and methods: Forty male Sprague-Dawley rats were divided into five groups: sham, renal IRI, renal IRI+NAC, renal IRI+E, and renal IRI+NAC+E. IR injury was induced by 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood samples were obtained for histopathological and biochemical evaluations.

Results: Renal IR resulted in increased malondialdehyde and nitrite/nitrate levels suggesting increased lipid peroxidation and peroxynitrite production and decreased superoxide dismutase and glutathione peroxidase activities. Both NAC and E alone significantly decreased malondialdehyde and nitrite/nitrate levels and increased superoxide dismutase and glutathione peroxidase activities. Additionally in the renal IRI+NAC+E group, all biochemical results were quite close to those of sham group. Histopathologically, the kidney injury in rats treated with combination of NAC and E was found significantly less than the other groups.

Conclusions: Both NAC and E are able to ameliorate IRI of the kidney by decreasing oxidative and nitrosative stresses and increasing free radical scavenger properties. Additionally, combination of NAC and E prevents kidney damage more than when each drug is used alone, suggesting that scavenging peroxynitrite nearby antioxidant activity is important in preventing renal IRI.

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Azoles / therapeutic use*
  • Drug Evaluation, Preclinical
  • Drug Therapy, Combination
  • Free Radical Scavengers / therapeutic use*
  • Isoindoles
  • Male
  • Organoselenium Compounds / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / prevention & control*

Substances

  • Azoles
  • Free Radical Scavengers
  • Isoindoles
  • Organoselenium Compounds
  • ebselen
  • Acetylcysteine