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World J Gastroenterol. Jun 7, 2006; 12(21): 3410-3415
Published online Jun 7, 2006. doi: 10.3748/wjg.v12.i21.3410
Experimental obstructive jaundice alters claudin-4 expression in intestinal mucosa: Effect of bombesin and neurotensin
Stelios F Assimakopoulos, Constantine E Vagianos, Aristides S Charonis, Ilias H Alexandris, Iris Spiliopoulou, Konstantinos C Thomopoulos, Vassiliki N Nikolopoulou, Chrisoula D Scopa
Stelios F Assimakopoulos, Department of Internal Medicine, School of Medicine, University of Patras, Patras, Greece
Constantine E Vagianos, Ilias H Alexandris, Department of Surgery, School of Medicine, University of Patras, Patras, Greece
Aristides S Charonis, Section of Histology, Center for Basic Research, Foundation of Biomedical Research of the Academy of Athens, Athens, Greece
Iris Spiliopoulou, Department of Microbiology, School of Medicine, University of Patras, Patras, Greece
Konstantinos C Thomopoulos, Vassiliki N Nikolopoulou, Department of Internal Medicine, Division of Gastroenterology, School of Medicine, University of Patras, Patras, Greece
Chrisoula D Scopa, Department of Pathology, School of Medicine, University of Patras, Patras, Greece
Correspondence to: Dr. Stelios F Assimakopoulos, Department of Internal Medicine, School of Medicine, University of Patras, Patras, Greece, PO Box 1174, 26110 Patras, Greece. sassim@upatras.gr
Telephone: +30-2610-990038 Fax: +30-2610-990775
Received: August 16, 2005
Revised: August 28, 2005
Accepted: November 18, 2005
Published online: June 7, 2006
Abstract

AIM: To investigate the influence of experimental obstructive jaundice and exogenous bombesin (BBS) and neurotensin (NT) administration on the expression of the tight junction (TJ)-protein claudin-4 in intestinal epithelium of rats.

METHODS: Forty male Wistar rats were randomly divided into five groups: I = controls, II = sham operated, III = bile duct ligation (BDL), IV = BDL+BBS (30 μg/kg per d), V = BDL+NT (300 μg/kg per d). At the end of the experiment on d 10, endotoxin was measured in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically and immunohistochemically for evaluation of claudin-4 expression in intestinal epithelium.

RESULTS: Obstructive jaundice led to intestinal barrier failure demonstrated by significant portal and aortic endotoxemia. Claudin-4 expression was significantly increased in the upper third of the villi in jaundiced rats and an upregulation of its lateral distribution was noted. Administration of BBS or NT restored claudin-4 expression to the control state and significantly reduced portal and aortic endotoxemia.

CONCLUSION: Experimental obstructive jaundice increases claudin-4 expression in intestinal epithelium, which may be a key factor contributing to the disruption of the mucosal barrier. Gut regulatory peptides BBS and NT can prevent this alteration and reduce portal and systemic endotoxemia.

Keywords: Obstructive jaundice; Tight junctions; Claudin-4; Intestinal permeability; Intestinal barrier; Regulatory peptides; Bombesin; Neurotensin