title: Protective effect of nimesulide against hepatic ischemia/reperfusion injury in rats: effects on oxidant/antioxidants, DNA mutation and COX-1/COX-2 levels.
abstract: BACKGROUND
  Nimesulide is a pharmacological agent and selective COX-2 inhibitor. It has anti-inflammatory, analgesic and antipyretic properties. The purpose of this study was to investigate the effect of nimesulide on oxidant/antioxidant, DNA mutation and COX-1/COX-2 activities in rat liver tissue with induced ischemia/reperfusion (I/R).
  
  
  METHODS
  Before the experiment, rats were divided into four groups; liver ischemia/reperfusion (LIR), 50mg/kg nimesulide+liver ischemia/reperfusion (NLIR50), 100mg/kg nimesulide+liver ischemia/reperfusion (NLIR100) and a control group to be given a sham operation (SG). Malondialdehyde (MDA), total glutathione (GSH) levels and myeloperoxidase (MPO), COX-1/COX-2 enzyme activities and DNA damage product level results from liver tissues and serum AST and ALT levels were determined. The data obtained were compared with the results from the liver ischemia/reperfusion and sham operation groups.
  
  
  RESULTS
  MDA levels, MPO and COX-2 activities and products of DNA injury were significantly lower in the groups given nimesulide, and particularly the NLIR100 group, compared to the LIR group (p<0.05), while tGSH levels were significantly higher (p<0.05). There was no significant difference between the NLIR50 and NLIR100 groups and the LIR group in terms of COX-1 levels (p>0.05). AST and ALT levels were significantly lower in the other groups compared to the LIR group (p<0.05).
  
  
  CONCLUSIONS
  Nimesulide at 100mg/kg prevented oxidative liver damage induced with I/R significantly better than at a dose of 50mg/kg. These experimental findings indicate that nimesulide may be useful in the treatment of hepatic I/R damage.
authors.affiliation: Ibni Sina Hospital, Department of General Surgery, Kayseri, Turkey.
authors.forename: Ismail
authors.initials: I
authors.lastname: Demiryilmaz
authors.affiliation: Diyarbakir Research and Educational hospital, Department of Pediatrics, Diyarbakir, Turkey.
authors.forename: Mehmet Ibrahim
authors.initials: MI
authors.lastname: Turan
authors.affiliation: Ataturk University, Faculty of Medicine, Department of Surgery, Erzurum, Turkey.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Kisaoglu
authors.affiliation: Ataturk University, Faculty of Medicine, Department of Biochemistry, Erzurum, Turkey.
authors.forename: Mine
authors.initials: M
authors.lastname: Gulapoglu
authors.affiliation: Erzincan University, Faculty of Medicine, Department of Surgery, Erzincan, Turkey.
authors.forename: Ismayil
authors.initials: I
authors.lastname: Yilmaz
authors.affiliation: Recep Tayyip Erdogan University, Faculty of Medicine, Department of Pharmacology, Rize, Turkey. Electronic address: halis.suleyman@gmail.com.
authors.forename: Halis
authors.initials: H
authors.lastname: Suleyman
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004249:DNA Damage / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology; D008111:Liver Function Tests; D008297:Male; D009154:Mutation; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D013449:Sulfonamides; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; C012655:nimesulide
keywords: Liver; Nimesulide; Oxidant/antioxidant; Rat