Effect of 5-lipoxygenase inhibition on Kupffer cell clearance capacity in obstructive jaundiced rats

Background. Obstructive jaundice is a common surgical problem. It may cause hepatic and Kupffer cell dysfunction. Previous studies demonstrated that 5-lipoxygenase inhibition prevents hepatic injury. However, its effect on Kupffer cell clearance capacity has not been determined yet. Materials and methods. Rats were divided into four groups. In group 1 (sham control group), only bile duct dissection was performed. In other groups bile ducts were ligated and divided. In groups 1 and 2 saline, in group 3 ethanol, and in group 4 a 5-lipoxygenase inhibitor AA-861 was given intraperitoneally to the animals. Rats were sacrificed 14 days after the operations. Serum alkaline phosphatase, total bilirubin, and alanine aminotransferase levels were determined. Kupffer cell clearance capacity was measured using an in situ isolated hepatic perfusion technique. Hematoxylin-eosin-stained liver samples were evaluated under light microscope for histopathologic scoring. Results. Rats in the sham control group had significantly lower serum ALP and bilirubin values than those in the experimental groups with biliary obstruction. AA-861 administration significantly decreased serum ALT levels and histopathologic scores. There was no significant difference in ALT levels and histopathologic scores between the sham control and AA-861 groups. Kupffer cell clearance capacity was found to be significantly increased in the AA-861 group compared to other experimental groups with obstructive jaundice. Conclusions. This study shows that leukotriene synthesis inhibition using AA-861 prevents hepatic damage and improves Kupffer cell clearance capacity in obstructive jaundiced rats. This may have significant implications for the management of patients with obstructive jaundice. (C) 2001 Academic Press.