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Colloidal bismuth subcitrate (CBS; De-Nol) exhibits gastroprotective properties in experimental animals and enhances the healing of chronic gastroduodenal ulcers, but the mechanisms of these actions have not been entirely elucidated. The present study was designed to determine whether epidermal growth factor (EGF), which also has gastroprotective and ulcer healing properties, contributes to the action of De-Nol on the stomach in rats. It was found that De-Nol protects the gastric mucosa against ethanol damage and that this is accompanied by increased mucosal generation of prostaglandins (PG). Removal of the endogenous source of EGF (sialoadenectomy) did not significantly decrease the protective and PG stimulating effects of De-Nol. Pretreatment with exogenous EGF partially protected the stomach against ethanol injury, but did not influence the protective action of De-Nol in sialoadenectomised animals. De-Nol, like EGF given orally, enhanced the healing of chronic gastric and duodenal ulcers induced by serosal acetic acid. De-Nol was found to bind EGF in a pH-dependent manner and to accumulate it in ulcer area. Thus the peptide is available locally in high concentrations to accelerate the re-epithelialisation and tissue repair of the ulcerated mucosa. These ulcer healing effects of De-Nol were reduced by sialoadenectomy and restored in part by oral administration of EGF. We conclude that salivary glands in rats are not essential for the gastroprotection induced by De-Nol, but seem to play an important role in the ulcer healing action of this drug possibly via an EGF mediated mechanism. [ABSTRACT FROM PUBLISHER]

This study compares the gastroprotective effects of colloidal bismuth subcitrate (De-Nol) with those of sucralfate and a methylated analogue of prostaglandin E2 (PGE2) against acute gastric lesions induced by acidified aspirin and absolute ethanol in rats. Both De-Nol and sucralfate given orally prevented dose dependently the formation of gastric lesions by these ulcerogens, De-Nol being, respectively, twice and seven times more potent, on a weight basis, than sucralfate. As the gastroprotective activities of both De-Nol and sucralfate on ethanol lesions can be reversed by pretreatment with indomethacin and as De-Nol and sucralfate increase the mucosal generation and luminal release of PGE2, we postulate that mucosal prostaglandins may be involved in the mechanism of action of these drugs on the gastric mucosa. [ABSTRACT FROM PUBLISHER]

Paracetamol or sodium salicylate given intragastrically 30 minutes before the administration of absolute ethanol or acidified aspirin dose-dependently reduced the formation of mucosal lesions. The generation of gastric mucosal prostaglandin-like activity increased with ethanol and was completely suppressed by acidified aspirin. Paracetamol or sodium salicylate given alone increased the generation of mucosal prostaglandin-like material. Indomethacin, the prostaglandin synthesis inhibitor, suppressed this effect and inhibited the protective influence of paracetamol or sodium salicylate on the production of gastric lesions. [ABSTRACT FROM PUBLISHER]

This study compares the effect of epidermal growth factor and prostaglandins (PGE2 or PGI2), applied topically to gastric mucosa, on gastric secretion and formation of ASA-induced gastric ulcerations in rats. Epidermal growth factor given topically in non-antisecretory doses prevented dose-dependently the formation of ASA-induced ulcers without affecting prostaglandin generation but with a significant rise in DNA synthesis in the oxyntic mucosa. The anti-ulcer effect of topical prostaglandins was also accompanied by an increase in DNA synthesis. This study indicates that topical epidermal growth factor, like PGE2 or PGI2, is cytoprotective and that this cytoprotection is not mediated by the inhibition of gastric secretion or prostaglandin formation but related to the increase in DNA synthesis in oxyntic mucosa. [ABSTRACT FROM PUBLISHER]

Background: Hp and NSAID such as aspirin (ASA) are independent risk factors of gastric ulcerogenesis but interaction between them remains unclear. Aim: to compare the ulcer healing effects of gastric inoculation with viable Hp and its water extracts (WE) with those of vehicle in animals with or without concurrent intragastric (i.g.) administration of acidified ASA (50 mg/kg/d) and rofecoxib (10 mg/kg/d) that started one week upon Hp and Hp-WE (series A) or prior to Hp, Hp-WE or saline inoculation (series B). Methods: Gastric ulcers (GU) were induced in rats by acetic acid. Animals were killed (day 12 and 20) upon Hp inoculation and ulcer induction. GU area, gastric blood flow (GBF), gastric mucus secretion and mRNA expression for IL-1beta and TNFalpha as well as gastrin, IL-1beta, and TNFalpha plasma concentrations were determined. Results: GU healed and reduced area by 59% and 97% in controls at day 12 and 20. Inoculation with Hp and Hp-WE or ASA and rofecoxib, each applied alone, delayed ulcer healing and decreased GBF but increased 2-3 fold IL-1beta and TNFalpha mRNA. In Hp-infected rats ASA or rofecoxib attenuated area of GU, plasma IL-1beta and TNFalpha levels but increased GBF comparing to ASA or rofecoxib applied alone. In contrast, ASA or rofecoxib, administrated before inoculation with Hp and Hp-WE, increased the ulcer area, IL-1beta and TNFalpha concentrations but reduced GBF significantly Conclusions: 1) GBF impairment in the ulcer area, over-expression and release of IL-1beta and TNFalpha may prolong ulcer healing induced by Hp and Hp-WE, 2) Hp induced gastric inflammation may limit ASA deleterious effect and suggest "protective" action of preexisting Hp infection, 3) delayed healing in rats treated with ASA and then exposed to Hp and Hp-WE could be due to the failure in gastric adaptation to these NSAID in newly Hp-infected gastric mucosa. [ABSTRACT FROM AUTHOR]

Background: Hp infection in Mongolian gerbils is an experimental model of gastric carcinogenesis. It remains unknown whether anti-Hp triple therapy influences pathological and functional aspects accompanying Hpinduced cancer cascade especially gastric acid secretion, gastric blood flow (GBF) and gastrin-somatostatin link. Aim: To compared the effects of intragastric (i.g.) inoculation of Mongolian gerbils with Hp strain (cagA+ vacA+) to those induced by vehicle in gerbils with or without gastric fistula at 2, 4, 12, 30 weeks upon gastric Hp inoculation. Methods: The effect of triple therapy (omeprazole, amoxicillin and tinidazol) was determined for 5 consecutive days starting from 24 h post infection. Histology, the viable Hp and density of Hp colonization were evaluated and the gastric blood flow (GBF), gastrin plasma and gastric luminal somatostatin were determined. Hp was detected by histology, culture and urease test. Results: Initial basal gastric acid (45 umol/h) in non-infected gerbils was reduced by 55% after Hp inoculation and persisted during time tested in Hp-infected but not in those with triple therapy. First lesions were seen 4 weeks after Hp inoculation and consisted of chronic gastritis with inflammatory cell infiltration, multiple gastric lymphoid follicle and typical adenomatous hyperplasia. In Hp-infected gerbils plasma gastrin concentration increased with significant fall of gastric somatostatin level and GBF. These effects were abolished in gerbils treated with anti-Hp triple therapy. Conclusions: 1) Hp-infection in Mongolian gerbils in early stages of adenocarcinoma formation results in the development of typical functional and pathological changes such as suppression of gastric secretion and impairment of both, gastric mucosal GBF and gastrin-somatostatin link and 2) this deleterious influence of Hp on gastric morphology and function could be reversed by anti-Hp triple therapy that prevent carcinogenesis in these species. [ABSTRACT FROM AUTHOR]

Background and Aims: LPS is the major virulence factor in Hp-infected stomach. Whether gastric mucosa can adapt to prolonged treatment with this endotoxin or water extract of Hp (WE-Hp) containing LPS and whether such adaptation can influence aspirin (ASA) induced gastric damage have been little studied. Methods: We compared the effect of single and 5-day repeated intragastric (i.g.) administration of Hp-LPS or WE-Hp with those induced by LPS isolated from Campylobacter jejuni, Yersinia enterocolitica and Bacteroides fragilis on gastric secretion in rats (series A) and acute gastric lesions induced at day 5 by ASA (series B). Hp-LPS and WE-Hp were prepared from antral biopsy of Hp-infected patients. Gastric blood flows (GBF) and lesions area were measured. Plasma leptin, gastrin, IL-1beta and TNFalpha were determined using RIA or ELISA. Gastric mucosa leptin mRNA was analyzed by RT-PCR. Results: Hp-LPS (0.01-5 mg/kg i.g.) or WE-Hp (1 ml i.g.) inhibited the gastric acid secretion (series A) and produced gastric damage which disappeared after 5 daily exposures. It was accompanied by GBF, plasma gastrin and leptin levels increase (series B). Intestinal LPS (1 mg/kg i.g.) inhibited gastric secretion and produced negligible damage also disappeared at day 5. ASA alone caused gastric lesions, decreased GBF and raised the plasma IL-1beta and TNFalpha levels 2-3 fold. The ASA damage was attenuated in rats treated 5 times with Hp-LPS and WE-Hp or intestinal LPS. These effects were accompanied by GBF increase, leptin mRNA upregulation, plasma immunoreactive leptin and gastrin concentration increase, IL-1beta and TNFalpha levels decrease. Conclusions: 1) Gastric mucosa may adapt to intestinal endotoxins similarly to that observed in Hp-LPS and WE-Hp treated mucosa and 2) adaptation to Hp cytotoxins enhances mucosal resistance to subsequent ASA damage possibly by inhibition of acid secretion, gastric microcirculation enhancement, proinflammatory cytokines attenuation and... [ABSTRACT FROM AUTHOR]