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


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.
Daglar
Gul
G
Department of Fourth Surgery, Ankara Numune Education and Research Hospital, Ankara, Turkey. guldaglar@yahoo.com
Karaca
Turgut
T
Yuksek
Yunus Nadi
YN
Gozalan
Ugur
U
Akbiyik
Filiz
F
Sokmensuer
Cenk
C
Gurel
Bora
B
Kama
Nuri Aydin
NA
D000085:Acetates / Q000627:therapeutic use*; D000818:Animals; D003521:Cyclopropanes; D004195:Disease Models, Animal; D007211:Indoles / Q000627:therapeutic use*; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use*; D008107:Liver Diseases / Q000517:prevention & control*; D008297:Male; D011804:Quinolines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D013440:Sulfides; D002722:Chlorobenzenes
D000085:Acetates; D003521:Cyclopropanes; D007211:Indoles; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors; D011804:Quinolines; D013440:Sulfides; C060893:MK-886; D002722:Chlorobenzenes; C093875:montelukast