title: Protective effects of simvastatin administered in the experimental hepatic ischemia-reperfusion injury rat model.
abstract: 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.
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey. Electronic address: dremelk@hotmail.com.
authors.forename: Fatma Emel
authors.initials: FE
authors.lastname: Kocak
authors.affiliation: Department of Physiology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
authors.forename: Aysegul
authors.initials: A
authors.lastname: Kucuk
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
authors.forename: Filiz
authors.initials: F
authors.lastname: Ozyigit
authors.affiliation: Department of Histology, Faculty of Medicine, Afyon Kocatepe University, Afyon, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Tosun
authors.affiliation: Department of Pathology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
authors.forename: Cengiz
authors.initials: C
authors.lastname: Kocak
authors.affiliation: Department of Histology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Kocak
authors.affiliation: Department of General Surgery, Evliya Celebi Education and Research Hospital, Dumlupinar University, Kutahya, Turkey.
authors.forename: Mehmet Fatih
authors.initials: MF
authors.lastname: Ekici
authors.affiliation: Department of General Surgery, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
authors.forename: Faik
authors.initials: F
authors.lastname: Yaylak
authors.affiliation: Department of Physiology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
authors.forename: Osman
authors.initials: O
authors.lastname: Genc
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008099:Liver / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D019821:Simvastatin / Q000627:therapeutic use*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin
keywords: Hepatic ischemia–reperfusion injury; Liver; Simvastatin