Effect of montelukast and MK-886 on hepatic ischemia-reperfusion injury in rats

J Surg Res. 2009 May 1;153(1):31-8. doi: 10.1016/j.jss.2008.02.052. Epub 2008 Mar 26.

Abstract

Background: Hepatic ischemia-reperfusion injury (I/R) may occur in transplantation, trauma, and elective hepatic resections. Leukotrienes have been shown to play a major role in hepatic I/R injury. Five-lipoxygenase enzyme is an important enzyme in the production of leukotrienes from arachidonic acid. MK-886 is an inhibitor of 5-lipoxygenase, and montelukast is a cysteinyl leukotriene receptor antagonist. The aim of this study was to investigate whether MK-886 and montelukast are effective in preventing hepatic I/R injury.

Materials and methods: Rats were divided into five groups consisting of seven rats in each: (1) Control I/R, (2) Control-montelukast, (3) Control-MK-886, (4) I/R+montelukast, and (5) I/R+MK-886. Thirty min of total hepatic vascular occlusion and then 60 min reperfusion were performed to animals in groups 1, 4, and 5. In groups 2 and 4, montelukast, and in groups 3 and 5, MK-886 was applied intraperitoneally before and during the surgical procedures.

Results: Apoptosis in the liver and intestine decreased significantly in the I/R+montelukast and I/R+MK-886 groups compared with the I/R group. Tissue malondialdehyde levels and glutathione consumptions also decreased significantly in the I/R+montelukast and I/R+MK-886 groups compared with the I/R group. The difference in serum alanine aminotransferase and aspartate aminotransferase levels between the groups did not reach significance.

Conclusions: Montelukast and MK-886 were found to be effective in prevention of liver and intestine injury by reducing apoptosis and oxidative stress in a hepatic I/R model. Anti-inflammatory properties and inhibition of lipid peroxidation by montelukast and MK-886 could be protective for these organs in I/R injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / therapeutic use*
  • Animals
  • Disease Models, Animal
  • Indoles / therapeutic use*
  • Leukotriene Antagonists / therapeutic use*
  • Lipoxygenase Inhibitors / therapeutic use*
  • Liver Diseases / prevention & control*
  • Male
  • Quinolines / therapeutic use*
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / prevention & control*

Substances

  • Acetates
  • Indoles
  • Leukotriene Antagonists
  • Lipoxygenase Inhibitors
  • Quinolines
  • MK-886
  • montelukast