A novel antioxidant non-steroidal anti-inflammatory agent protects rat liver against ischemia-reperfusion injury

In Vivo. 2004 Mar-Apr;18(2):161-9.

Abstract

Liver ischemia followed by reperfusion is an important and common clinical event. A major mechanism is leukocyte adhesion to endothelium followed by release of reactive oxygen metabolites. The aim of this study was to determine the effects of a novel antioxidant ethylenediamine derivative with anti-inflammatory properties (compound IA) on an imitated clinical setting of acute hepatic ischemia-reperfusion injury. Eight groups of rats were subjected to a model of hepatic ischemia that was produced by occluding for 30 min the portal vein and hepatic artery. At the end of ischemia, compound IA was administered intravenously and the clamps were removed allowing reperfusion for 60 min or 24 h. The effect of compound IA was evaluated by histopathological examination, lipid peroxidation and plasma levels of liver enzymes. Administration of compound IA resulted in significantly less histological damage in liver tissue after 30-min ischemia followed by 60-min and 24-h reperfusion. Ischemia followed by 60 min of reperfusion increased lipid peroxidation compared to the sham-operated and the non-ischemic group. This increase was attenuated in the group treated with compound IA. Serum enzyme levels were significantly higher in the reperfusion groups compared to the non-ischemic groups and diminished after treatment. Compound IA exerted a protective effect on hepatic reperfusion injury in rats. Compound IA is believed to act by means of its potent antioxidant and anti-inflammatory activities.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antioxidants / pharmacology*
  • Aspartate Aminotransferases / blood
  • Disease Models, Animal
  • Ethylamines / pharmacology*
  • L-Lactate Dehydrogenase / blood
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / pathology
  • Male
  • Malondialdehyde / metabolism
  • Pentanes / pharmacology*
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / blood
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*

Substances

  • 5-(2-amino-ethylamino)-1-phenyl-2-pentanone
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Ethylamines
  • Pentanes
  • Malondialdehyde
  • L-Lactate Dehydrogenase
  • Aspartate Aminotransferases
  • Alanine Transaminase