epidermal-growth-factor and bismuth-tripotassium-dicitrate

In recent years considerable progress has been made to elucidate the modes of action of colloidal bismuth subcitrate (CBS). CBS accelerates the healing of experimental chronic ulcers in rats by the formation of occlusive complexes and/or the accumulation of epidermal growth factor (EGF) in the ulcer crater. CBS exhibits gastric protection (cytoprotection) against, for example, ethanol lesions. Microscopic analysis of these lesions reveals that CBS protects against deep mucosal necrosis but not superficial injury, a property also found with prostaglandins. Dose-dependent increases in gastric prostaglandin E2 (PGE2) and bicarbonate secretion were found after CBS, in both animals and human volunteers. CBS in normal clinical doses increases PGE2 output from the gastric mucosa of human volunteers. Gastric injury in human volunteers produced by unbuffered aspirin is also reduced by concomitant administration of CBS, whereby PGE2 production is inhibited. This indicates that CBS exerts its gastric protection by both prostaglandin- and non-prostaglandin-mediated mechanisms. Campylobacter pylori is considered to be a causative factor of chronic antral gastritis and is a potential prerequisite for peptic ulcer disease. CBS, in contrast to other anti-ulcer drugs, prevents the growth of C. pylori in vitro. CBS eradicates C. pylori in patients and resolves chronic antral gastritis. The favourable relapse rates with CBS might be explained by the permanent eradication of C. pylori.

Topics: Animals; Anti-Ulcer Agents; Campylobacter; Epidermal Growth Factor; Gastric Mucosa; Humans; Organometallic Compounds; Wound Healing

The effect of an antiulcer drug, colloidal bismuth subcitrate (De-Nol), on the proteolytic activity of pepsin toward gastric mucus and salivary epidermal growth factor was investigated. Samples of pig gastric mucus and mouse epidermal growth factor were incubated with pepsin in the absence and in the presence of De-Nol, and the released alpha-amino acid residues were quantified. Results of analysis revealed that, in the absence of De-Nol, the apparent Km value of pepsin toward gastric mucus was 1.4 g/L and that towards epidermal growth factor 120 microM. Introduction of De-Nol to the incubation mixtures led, in both cases, to reduction of the rates of proteolysis. With gastric mucus, the rate of proteolysis inhibition was proportional to the De-Nol concentration up to 1 x 10(-2) g/L, at which point a 54% reduction in mucus proteolysis occurred, whereas, with epidermal growth factor, this concentration of De-Nol caused nearly 52% inhibition in the rate of proteolysis. The apparent Ki value for peptic degradation of gastric mucus in the presence of De-Nol was 2.1 x 10(-4) g/L and that for peptic degradation of epidermal growth factor 1.8 x 10(-2) g/L. The results suggest that among the beneficial effects of colloidal bismuth subcitrate on ulcer healing is its ability to interfere with peptic digestion of the protective gastric mucus coat and of such important bioactive protein as epidermal growth factor.

Topics: Animals; Anti-Ulcer Agents; Bismuth; Epidermal Growth Factor; In Vitro Techniques; Mice; Mucus; Organometallic Compounds; Pepsin A; Swine

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.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Anti-Ulcer Agents; Bismuth; Epidermal Growth Factor; ErbB Receptors; Gastric Mucosa; Male; Organometallic Compounds; Peptic Ulcer; Rats; Rats, Inbred Strains; Submandibular Gland