N-Acetylcysteine and High-Dose Atorvastatin Reduce Oxidative Stress in an Ischemia-Reperfusion Model in the Rat Kidney

Transplant Proc. 2015 Nov;47(9):2757-62. doi: 10.1016/j.transproceed.2015.09.035.

Abstract

Objective: To investigate the effects of N-acetylcysteine (NAC) and high-dose atorvastatin (ATOR) in reducing oxidative stress in a rat kidney model of ischemia-reperfusion injury.

Methods: Forty female rats underwent clamping of the left renal artery for 30 minutes, followed by reperfusion. The effects of pre-ischemic administration of NAC and/or ATOR were evaluated within 4 groups: a) control (no NAC, no ATOR); b) NAC (intraperitoneal NAC administration); c) ATOR (oral ATOR administration); and d) NAC+ATOR (both drugs). Oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and myeloperoxidase (MPO). Post-ischemia-reperfusion injury was evaluated by means of renal histology.

Results: NAC, ATOR, and NAC+ATOR in rats showed lower MPO (P < .05) and higher GPx activity (P < .05) versus control; SOD activity was lower in NAC versus ATOR (P < .05). No difference among groups was found at histology. However, a lower rate of tubular ischemic lesions was evident in NAC+ATOR versus control (P = .07).

Conclusions: Atorvastatin pretreatment provides protection against oxidative stress in a rat kidney model of ischemia-reperfusion injury, reinforcing the evidence of a beneficial effect of statins beyond their cholesterol-lowering properties.

MeSH terms

  • Acetylcysteine / pharmacology*
  • Animals
  • Atorvastatin / administration & dosage
  • Atorvastatin / pharmacology*
  • Catalase / metabolism
  • Female
  • Free Radical Scavengers / pharmacology*
  • Glutathione Peroxidase / metabolism
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Kidney / blood supply
  • Kidney / injuries
  • Kidney / pathology
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / metabolism
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Peroxidase / metabolism
  • Rats
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Superoxide Dismutase / metabolism

Substances

  • Free Radical Scavengers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Atorvastatin
  • Catalase
  • Peroxidase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Acetylcysteine