Edaravone inhibits apoptosis caused by ischemia/reperfusion injury in a porcine hepatectomy model

World J Gastroenterol. 2012 Jul 21;18(27):3520-6. doi: 10.3748/wjg.v18.i27.3520.

Abstract

Aim: To investigate the effect of E3-methyl-1-phenyl-2-pyrazolin-5-one (Edr) on hepatic ischemia-reperfusion (I/R) injury and liver regeneration in a porcine hepatectomy model.

Methods: One hour ischemia was induced by occluding the vessels and the bile duct of the right and median lobes. A 40% left hepatectomy was performed after reperfusion. Six animals received Edr (3 mg/kg per hour) intravenously and six control animals received saline just before reperfusion. Remnant liver volume, hemodynamics, aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase and lactic acid, were compared between the groups. The expression of transforming growth factor-β (TGF-β1) and toll-like receptor (TRL) mRNA in hepatic tissues was examined using reverse transcription polymerase chain reaction. Apoptosis was demonstrated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, respectively.

Results: Serum AST (P = 0.029), and toll like receptor 4 level (P = 0.043) were significantly lower after 3 h in animals receiving Edr. In addition, TUNEL staining in Edr-treated pigs showed significantly fewer hepatocytes undergoing apoptosis compared with control pigs. After 1 mo, all factors were non-significantly different between the two groups.

Conclusion: Edr is considered to reduce hepatic injury in the early stage of I/R injury in a porcine model.

Keywords: Edaravone; Ischemia-reperfusion injury; Liver resection; Toll like receptor 4; Transforming growth factor-β.

MeSH terms

  • Animals
  • Antipyrine / analogs & derivatives*
  • Antipyrine / pharmacology
  • Apoptosis / drug effects*
  • Biomarkers / blood
  • Cytoprotection
  • Disease Models, Animal
  • Edaravone
  • Free Radical Scavengers / pharmacology*
  • Gene Expression Regulation
  • Hepatectomy / adverse effects*
  • In Situ Nick-End Labeling
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Liver Regeneration / drug effects
  • Male
  • Real-Time Polymerase Chain Reaction
  • Reperfusion Injury / etiology
  • Reperfusion Injury / genetics
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Swine
  • Time Factors

Substances

  • Biomarkers
  • Free Radical Scavengers
  • Edaravone
  • Antipyrine