Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2005; 11(43): 6757-6764
Published online Nov 21, 2005. doi: 10.3748/wjg.v11.i43.6757
Effect of bombesin and neurotensin on gut barrier function in partially hepatectomized rats
Stelios F Assimakopoulos, Ilias H Alexandris, Chrisoula D Scopa, Panagiotis G Mylonas, Konstantinos C Thomopoulos, Christos D Georgiou, Vassiliki N Nikolopoulou, Constantine E Vagianos
Stelios F Assimakopoulos, Department of Internal Medicine, School of Medicine, University of Patras, Patras, Greece
Ilias H Alexandris, Constantine E Vagianos, Department of Surgery, School of Medicine, University of Patras, Patras, Greece
Chrisoula D Scopa, Department of Pathology, School of Medicine, University of Patras, Patras, Greece
Panagiotis G Mylonas, Department of Internal Medicine, Division of Endocrinology, 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
Christos D Georgiou, Department of Biology, Division of Genetics, Cell and Developmental Biology, University of Patras, Patras, Greece
Author contributions: All authors contributed equally to the work.
Correspondence to: Constantine E Vagianos, MD, Associate Professor, Department of Surgery, University of Patras, Medical School, Rion University Hospital, 26500 Patras, Greece.
Telephone: +30-2610-999 779 Fax: +30-2610-993 984
Received: March 28, 2005
Revised: April 23, 2005
Accepted: April 26, 2005
Published online: November 21, 2005

AIM: To investigate the effect of regulatory peptides bombesin (BBS) and neurotensin (NT) on intestinal barrier function in partially hepatectomized rats.

METHODS: Ninety male Wistar rats were randomly divided into five groups: I (n = 10): controls, II (n = 20): sham operated, III (n = 20): partial hepatectomy 70% (PHx), IV (n = 20): PHx+BBS (30 μg/kg/d), V (n = 20): PHx+NT (300 μg/kg/d). Groups IV and V were treated for 8 days before PHx and 48 h post surgery. At the end of the experiment, on day 10, intestinal barrier function was assessed by measuring endotoxin concentrations in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically and villus density, mucosal thickness, mitotic activity and apoptosis in crypts were assessed. In addition, ileal mucosa was analyzed for DNA and protein content and microbiological analysis was performed in cecal contents. To estimate intestinal oxidative stress, lipid peroxidation was determined on tissue homogenates from terminal ileum.

RESULTS: BBS or NT administration significantly reduced portal and systemic endotoxemia observed 48 h after partial hepatectomy. In hepatectomized rats (group III), a trend towards induction of mucosal atrophy was observed, demonstrated by the reduction of villus density, mucosal thickness, protein content and significant reduction of DNA, while these alterations were reversed by regulatory peptides administration. This trophic effect of BBS and NT was accompanied by induction of mitoses above control levels and a significant reduction of apoptosis in intestinal crypts. Intestinal lipid peroxidation was found significantly lower in PHx group and regulatory peptides exerted an antioxidant action, further decreasing this parameter of oxidative stress. The bacterial population of E. coli and aerobic Gram (+) cocci was increased in cecal content of hepatectomized rats, while this parameter was not affected by the administration of BBS or NT.

CONCLUSION: Gut regulatory peptides BBS and NT improve intestinal barrier function and reduce endotoxemia in experimental partial hepatectomy. This effect is, at least in part, mediated by their trophic, antiapoptotic, mitogenic, and antioxidant effect on the intestinal epithelium. This observation might be of potential value in patients undergoing liver resection.

Keywords: Hepatectomy, Rats, Bombesin, Neurotensin, Intestinal barrier, Apoptosis, Oxidative stress