Acute protective effects of simvastatin in the rat model of renal ischemia-reperfusion injury: it is never too late for the pretreatment

J Pharmacol Sci. 2008 Aug;107(4):465-70. doi: 10.1254/jphs.sc0070374.

Abstract

Acute pretreatment with a single i.v. bolus injection of simvastatin (1 mg/kg) significantly protects rat kidney injured by ischemia-reperfusion (I/R) (45 min + 6 h). We aimed to determine the optimal timing of such a pretreatment. The effects of both injections of simvastatin before ischemia and reperfusion were similar regarding total histological score. However, simvastatin injected 30 min before ischemia was 30% - 75% more effective in reduction of serum creatinine levels and interstitial edema score, while its injections 5 and 30 min before reperfusion were 25% - 60% more effective in reduction of tubular necrosis score and fractional excretion of Na+. However, the observed differences do not seem to offer significant advantage in clinical settings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Creatinine / blood
  • Disease Models, Animal
  • Drug Administration Schedule
  • Edema / pathology
  • Edema / prevention & control
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Injections, Intravenous
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney Tubular Necrosis, Acute / pathology
  • Kidney Tubular Necrosis, Acute / prevention & control
  • Male
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Simvastatin / administration & dosage
  • Simvastatin / pharmacology*
  • Sodium / urine
  • Time Factors

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Sodium
  • Simvastatin
  • Creatinine