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

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.

• Authors: Gul Daglar, Turgut Karaca, Yunus Nadi Yuksek, Ugur Gozalan, Filiz Akbiyik, Cenk Sokmensuer, Bora Gurel, Nuri Aydin Kama
• Journal: The Journal of surgical research (J Surg Res) Vol. 153 Issue 1 Pg. 31-8 (May 01 2009) ISSN: 1095-8673 [Electronic] United States
• PMID: 18656901 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Acetates (therapeutic use)
• Animals
• Cyclopropanes
• 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)
• Sulfides