Protective effects of simvastatin administered in the experimental hepatic ischemia-reperfusion injury rat model

J Surg Res. 2015 Dec;199(2):393-401. doi: 10.1016/j.jss.2015.06.009. Epub 2015 Jun 12.


Background: Hepatic ischemia-reperfusion (I/R) injury is a major complication in clinical practice. Previous studies suggest that statins have pleiotropic effects in addition to cholesterol-lowering effects. In this study, we aimed to investigate the hepatoprotective role of two different doses of simvastatin (SV) pretreatment in rats with experimental hepatic I/R injury.

Methods: Adult male Sprague-Dawley rats were divided into four groups (n = 7 in each group) :control, I/R, I/R with 2.5-mg/kg SV, and I/R with 5.0-mg/kg SV. Before hepatic I/R was induced, SV was injected intraperitoneally at doses of 2.5 and 5.0 mg/kg. After 45-min ischemia and a 60-min reperfusion period, the animals were euthanized, and liver tissues were excised. Tissue levels of malondialdehyde and nitric oxide, and activities of superoxide dismutase, glutathione peroxidase, and catalase were measured. Liver tissues were also evaluated histopathologically and immunohistochemically.

Results: Histopathologic evaluation showed that 5.0-mg/kg SV reduced hepatic damage and apoptosis. Pretreatment with 5.0-mg/kg SV reduced malondialdehyde and nitric oxide levels (P < 0.01) and increased superoxide dismutase, glutathione peroxidase, and catalase activities significantly (P < 0.001, P < 0.01) in I/R with 2.5-mg/kg SV compared with I/R group. In addition, SV decreased Kupffer cell activation, and hypoxia-inducible factor-1α and vascular endothelial growth factor protein levels.

Conclusions: The results of this study suggest that 5.0-mg/kg SV pretreatment may be protective against hepatic I/R injury. This effect can be achieved by antioxidant and antiapoptotic activities.

Keywords: Hepatic ischemia–reperfusion injury; Liver; Simvastatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Liver / blood supply*
  • Liver / enzymology
  • Liver / pathology
  • Liver Diseases / pathology
  • Liver Diseases / prevention & control*
  • Male
  • Random Allocation
  • Rats, Sprague-Dawley
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Simvastatin / therapeutic use*


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Simvastatin