Triple eradication therapy counteracts functional impairment associated with Helicobacter pylori infection in Mongolian gerbils.

Abstract

Gastric Helicobacter pylori (Hp) infection in Mongolian gerbils is an established experimental model of gastric carcinogenesis resulting from the long-term Hp infection but functional aspects accompanying this Hp-induced progression from gastritis to the cancer, especially changes in gastric acid secretion, gastric blood flow (GBF) and gastrin-somatostatin link have been little studied. It is unclear whether Hp eradication therapy alters the functional and the histopathological changes in this animal model of Hp-infection. We examined the effects of intragastric (i.g.) inoculation of Mongolian gerbils with Hp strain (cagA+ vacA+, 5 x 10(6) CFU/ml) that had been isolated from a patient with gastric ulcer as compared to those induced by vehicle (saline) in gerbils with or without gastric fistula (GF) at 1.2, 4, 6, 9, 12 and 30 wks upon gastric inoculation with this bacteria. An attempt was made to evaluate the influence of anti-Hp triple therapy with omeprazole, amoxicillin and tinidazol on gastric Hp-infection and Hp-induced functional impairment of the gastric mucosa. Gastric mucosal biopsy specimens were taken for the assessment of the morphological changes and the presence of Hp infection using rapid urease test (CLO-test) and the density of Hp-colonization were assessed by counting of the number of bacterial colonies per plate. Gastric blood flow (GBF) was measured by H2-gas clearance technique and the venous blood and the gastric content were collected for the measurement of plasma gastrin levels and the gastric luminal somatostatin level by radioimmunoassay (RIA). The Hp in gastric mucosa was detected in all animals by culture and rapid urease test at various periods upon Hp inoculation. Basal gastric acid in non-infected conscious gerbils with GF reached the level of about 28 +/- 4 micromol/h and this was reduced by over 50% immediately upon the Hp-inoculation and persisted for time intervals tested up to 30 wk. Early lesions were seen 4 wks after the Hp-inoculation and consisted of chronic gastritis with thickened gastric mucosal foldings and elongated interfoveolar ridges. Edema and congestion as well as significant mucosal inflammatory infiltration with lymphoid infiltrate in lamina propria of the mucosa occurred in all infected gerbils. Adenomatous hyperplasia with cellular atypia was observed at 12 wk upon Hp-inoculation together with increased mitotic activity and numerous apoptotic bodies formation, while lamina propria was reduced leaving dilated atypical gastric gland situated "back-to-back". This glandular atypia failed to show lamina propria or submucosa infiltration corresponding to gastric intraepithelial neoplasia. The GBF in Hp-infected gerbils was significantly lower, and a 6-7 fold increase in plasma gastrin levels combined with a significant fall in gastric luminal somatostatin contents observed at all tested periods as compared to vehicle-controls and these effects were counteracted by anti-Hp triple therapy. We conclude that: 1). Hp-infection in Mongolian gerbils in early stages before adenocarcinoma formation results in the development of typical functional and pathological changes such as suppression of gastric secretion and impairment of both, gastric mucosal microcirculation and gastrin-somatostatin link, and 2). this deleterious influence of Hp on gastric morphology and gastric functions is greatly attenuated in gerbils treated with Hp-eradication therapy.

• Authors: T Brzozowski, P C Konturek, S Kwiecien, S J Konturek, R Pajdo, D Drozdowicz, A Ptak, M Pawlik, J Stachura, W W Pawlik, E G Hahn
• Journal: Journal of physiology and pharmacology : an official journal of the Polish Physiological Society (J Physiol Pharmacol) Vol. 54 Issue 1 Pg. 33-51 (Mar 2003) ISSN: 0867-5910 [Print] Poland
• PMID: 12674217 (Publication Type: Journal Article)

Chemical References

• Anti-Ulcer Agents
• Gastrins
• Penicillins
• Tinidazole
• Somatostatin
• Amoxicillin
• Omeprazole

Topics

• Amoxicillin (pharmacology)
• Animals
• Anti-Ulcer Agents (pharmacology)
• Colony Count, Microbial
• Drug Therapy, Combination (pharmacology)
• Gastric Mucosa (drug effects, microbiology, pathology)
• Gastrins (blood, drug effects, metabolism)
• Gerbillinae
• Helicobacter Infections (complications, drug therapy, metabolism)
• Helicobacter pylori (drug effects, isolation & purification)
• Hyperplasia
• Microcirculation
• Omeprazole (pharmacology)
• Penicillins (pharmacology)
• Radioimmunoassay
• Somatostatin (metabolism)
• Stomach Ulcer (drug therapy, metabolism, microbiology)
• Tinidazole (pharmacology)