Experimental obstructive jaundice disrupts intestinal mucosal barrier by altering occludin expression: beneficial effect of bombesin and neurotensin.

Abstract

Little is known of the molecular events leading to increased intestinal permeability in obstructive jaundice. This study was undertaken to investigate the influence of experimental obstructive jaundice on the expression of the tight junction-associated protein occludin in the intestinal epithelium. Seventy male Wistar rats were randomly divided into five groups: I, controls; II, sham-operated; III, bile duct ligation (BDL); IV, BDL+Bombesin (BBS) (30 microg/kg/d); and V, BDL+Neurotensin (NT) (300 microg/kg/d). At the end of the experiment, on day 10, endotoxin was measured in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically and immunohistochemically for evaluation of occludin expression in the intestinal epithelium. Lipid peroxidation and protein oxidation were determined on tissue homogenates from terminal ileum and microbiologic analysis was performed in cecal contents. Obstructive jaundice resulted in portal and aortic endotoxemia, which was significantly reduced after BBS or NT administration. In the BDL group, there was total loss of occludin expression in numerous enterocytes mainly at the upper third of the villi, while a gradient of positivity existed from crypt to tip. Occludin expression was restored to control state after treatment with BBS or NT. In addition, both peptides reduced intestinal lipid peroxidation, while BBS reduced protein oxidation as well. Experimental obstructive jaundice induces regional loss of occludin expression in the intestinal epithelium, which may be a key factor contributing to the disruption of the mucosal barrier. Gut regulatory peptides BBS and NT prevent this alteration, leading to lower portal and systemic endotoxemia.