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. 1988 Jul;29(7):894–902. doi: 10.1136/gut.29.7.894

Epidermal growth factor (EGF) in the gastroprotective and ulcer healing actions of colloidal bismuth subcitrate (De-Nol) in rats.

S J Konturek 1, A Dembinski 1, Z Warzecha 1, W Bielanski 1, T Brzozowski 1, D Drozdowicz 1
PMCID: PMC1433772  PMID: 3260885

Abstract

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.

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Selected References

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  1. Chen L. B., Gudor R. C., Sun T. T., Chen A. B., Mosesson M. W. Control of a cell surface major glycoprotein by epidermal growth factor. Science. 1977 Aug 19;197(4305):776–778. doi: 10.1126/science.302030. [DOI] [PubMed] [Google Scholar]
  2. Dembiński A., Gregory H., Konturek S. J., Polański M. Trophic action of epidermal growth factor on the pancreas and gastroduodenal mucosa in rats. J Physiol. 1982 Apr;325:35–42. doi: 10.1113/jphysiol.1982.sp014133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Forgue-Lafitte M. E., Laburthe M., Chamblier M. C., Moody A. J., Rosselin G. Demonstration of specific receptors for EGF--urogastrone in isolated rat intestinal epithelial cells. FEBS Lett. 1980 Jun 2;114(2):243–246. doi: 10.1016/0014-5793(80)81125-2. [DOI] [PubMed] [Google Scholar]
  4. Gresik E. W., van der Noen H., Barka T. Epidermal growth factor-like material in rat submandibular gland. Am J Anat. 1979 Sep;156(1):83–89. doi: 10.1002/aja.1001560108. [DOI] [PubMed] [Google Scholar]
  5. Hall D. W., van den Hoven W. E. Gastric mucosa protection and prostaglandin E2 generation in rats by colloidal bismuth subcitrate (DE-NOL). Arch Int Pharmacodyn Ther. 1987 Apr;286(2):308–319. [PubMed] [Google Scholar]
  6. Hamilton I., O'Connor H. J., Wood N. C., Bradbury I., Axon A. T. Healing and recurrence of duodenal ulcer after treatment with tripotassium dicitrato bismuthate (TDB) tablets or cimetidine. Gut. 1986 Jan;27(1):106–110. doi: 10.1136/gut.27.1.106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hamilton I., Worsley B. W., O'Connor H. J., Axon A. T. Effects of tripotassium dicitrato bismuthate (TDB) tablets or cimetidine in the treatment of duodenal ulcer. Gut. 1983 Dec;24(12):1148–1151. doi: 10.1136/gut.24.12.1148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kang J. Y., Piper D. W. Cimetidine and colloidal bismuth in treatment of chronic duodenal ulcer. Comparison of initial healing and recurrence after healing. Digestion. 1982;23(2):73–79. doi: 10.1159/000198690. [DOI] [PubMed] [Google Scholar]
  9. Kirkegaard P., Olsen P. S., Nexø E., Holst J. J., Poulsen S. S. Effect of vasoactive intestinal polypeptide and somatostatin on secretion of epidermal growth factor and bicarbonate from Brunner's glands. Gut. 1984 Nov;25(11):1225–1229. doi: 10.1136/gut.25.11.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Konturek S. J., Brzozowski T., Piastucki I., Dembinski A., Radecki T., Dembinska-Kiec A., Zmuda A., Gregory H. Role of mucosal prostaglandins and DNA synthesis in gastric cytoprotection by luminal epidermal growth factor. Gut. 1981 Nov;22(11):927–932. doi: 10.1136/gut.22.11.927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Konturek S. J., Radecki T., Brzozowski T., Piastucki I., Dembiński A., Dembińska-Kieć A., Zmuda A., Gryglewski R., Gregory H. Gastric cytoprotection by epidermal growth factor. Role of endogenous prostaglandins and DNA synthesis. Gastroenterology. 1981 Sep;81(3):438–443. [PubMed] [Google Scholar]
  12. Konturek S. J., Radecki T., Piastucki I., Brzozowski T., Drozdowicz D. Gastrocytoprotection by colloidal bismuth subcitrate (De-Nol) and sucralfate. Role of endogenous prostaglandins. Gut. 1987 Feb;28(2):201–205. doi: 10.1136/gut.28.2.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Konturek S. J., Stachura J., Radecki T., Drozdowicz D., Brzozowski T. Cytoprotective and ulcer healing properties of prostaglandin E2, colloidal bismuth and sucralfate in rats. Digestion. 1987;38(2):103–113. doi: 10.1159/000199579. [DOI] [PubMed] [Google Scholar]
  14. Lee S. P. A potential mechanism of action of colloidal bismuth subcitrate: diffusion barrier to hydrochloric acid. Scand J Gastroenterol Suppl. 1982;80:17–21. [PubMed] [Google Scholar]
  15. Lembach K. J. Enhanced synthesis and extracellular accumulation of hyaluronic acid during stimulation of quiescent human fibroblasts by mouse epidermal growth factor. J Cell Physiol. 1976 Oct;89(2):277–288. doi: 10.1002/jcp.1040890211. [DOI] [PubMed] [Google Scholar]
  16. Moshal M. G., Gregory M. A., Pillay C., Spitaels J. M. Does the duodenal cell ever return to normal? A comparison between treatment with cimetidine and denol. Scand J Gastroenterol Suppl. 1979;54:48–51. [PubMed] [Google Scholar]
  17. Okabe S., Roth J. L., Pfeiffer C. J. A method for experimental, penetrating gastric and duodenal ulcers in rats. Observations on normal healing. Am J Dig Dis. 1971 Mar;16(3):277–284. doi: 10.1007/BF02235252. [DOI] [PubMed] [Google Scholar]
  18. Olsen P. S., Kirkegaard P., Poulsen S. S., Nexø E. Adrenergic effects on exocrine secretion of rat submandibular epidermal growth factor. Gut. 1984 Nov;25(11):1234–1240. doi: 10.1136/gut.25.11.1234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Olsen P. S., Poulsen S. S., Kirkegaard P., Nexø E. Role of submandibular saliva and epidermal growth factor in gastric cytoprotection. Gastroenterology. 1984 Jul;87(1):103–108. [PubMed] [Google Scholar]
  20. Olsen P. S., Poulsen S. S., Therkelsen K., Nexø E. Effect of sialoadenectomy and synthetic human urogastrone on healing of chronic gastric ulcers in rats. Gut. 1986 Dec;27(12):1443–1449. doi: 10.1136/gut.27.12.1443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Skinner K. A., Soper B. D., Tepperman B. L. Effect of sialoadenectomy and salivary gland extracts on gastrointestinal mucosal growth and gastrin levels in the rat. J Physiol. 1984 Jun;351:1–12. doi: 10.1113/jphysiol.1984.sp015227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Skinner K. A., Tepperman B. L. Influence of desalivation on acid secretory output and gastric mucosal integrity in the rat. Gastroenterology. 1981 Aug;81(2):335–339. [PubMed] [Google Scholar]
  23. Skov Olsen P., Poulsen S. S., Therkelsen K., Nexø E. Oral administration of synthetic human urogastrone promotes healing of chronic duodenal ulcers in rats. Gastroenterology. 1986 Apr;90(4):911–917. doi: 10.1016/0016-5085(86)90867-x. [DOI] [PubMed] [Google Scholar]
  24. Takeuchi K., Johnson L. R. Effect of cell proliferation on healing of gastric and duodenal ulcers in rats. Digestion. 1986;33(2):92–100. doi: 10.1159/000199280. [DOI] [PubMed] [Google Scholar]
  25. Takeuchi K., Johnson L. R. Pentagastrin protects against stress ulceration in rats. Gastroenterology. 1979 Feb;76(2):327–334. [PubMed] [Google Scholar]
  26. Ulshen M. H., Lyn-Cook L. E., Raasch R. H. Effects of intraluminal epidermal growth factor on mucosal proliferation in the small intestine of adult rats. Gastroenterology. 1986 Nov;91(5):1134–1140. doi: 10.1016/s0016-5085(86)80008-7. [DOI] [PubMed] [Google Scholar]
  27. Vantrappen G., Rutgeerts P., Broeckaert L., Janssens J. Randomised open controlled trial of colloidal bismuth subcitrate tablets and cimetidine in the treatment of duodenal ulcer. Gut. 1980 Apr;21(4):329–333. doi: 10.1136/gut.21.4.329. [DOI] [PMC free article] [PubMed] [Google Scholar]

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