Effect of probiotics and triple eradication therapy on the cyclooxygenase (COX)-2 expression and functional impairment in Helicobacter pylori (Hp)-Infected mongolian gerbis

Abstract

Hp infection in Mongolian gerbils is an established experimental model of gastritis, peptic ulcers and finally adenocarcinoma. It remains unknown whether probiotic and anti-Hp triple therapy influence functional aspects accompanying this Hp-induced cancer cascade especially gastric acid secretion, gastric blood flow (GBF), gastrin-somatostatin link and mucosal COX2 expression. We compared the effects of intragastric (i.g.) inoculation of Hp strain (cagA + vacA+, 5x106 CFU/m[) or vehicle (saline) in gerbils with or without gastric fistula at 2, 12 and 30 weeks upon gastric Hp inoculation. The effect of triple therapy including omeprazole (10 mg/kg s.c.), amoxicifiin and tinidazol (both 15 mg/kg i.g.) and Lactobacillns rhamnosus & Lactobacillus acidophilus (LA, Rossel Inc. Canada, 2x109 CFU/ml) on Hp-infection was determined for 5 consecutive days starting from 24 h post infection. Histology of glandular mucosa and density of Hp-colonization were evaluated. The GBF was measured by H2-gas clearance method, plasma gastrin and gastric luminal somatostatin were determined by RIA and mucosal COX-2 protein expression was assessed by Western Blot. The gastric Hp infection was detected in all animals by histology, Hp culture and urease test. Basal gastric acid in non-infected gerbils was reduced by over 65% immediately after Hp inoculation and persisted at all the time intervals compared to those in non-infected gerbils. Hp-infected mucosa showed chronic gastritis with marked inflammatory cell infiltration and formation of multiple gastric lymphoid follicles and typical adenomatons hyperplasia with increased mitotic activity and apoptotic bodies formation and these changes were counteracted by LA and anti-Hp therapy. The fall in GBF and 6-7 folds increase in plasma gastrin and the significant fall in gastric somatostatin levels and overexpression of COX-2 protein were observed and these effects were reversed in animals treated with anti-Hp triple therapy and significantly attenuated by the concurrent treatment with LA. We conclude that probiotics such as LA and anti-Hp triple therapy counteract the development of typical pathological and functional changes in Hp-infected Mongolian gerbils in early stages of adenocarcinoma formation that is accompanied by suppression of gastric secretion, impairment of both, gastric microcirculation and gastrin-somatostatin link and overexpression of COX-2.