Skip to main content
SpringerLink
Log in

Effects of cholestyramine and synthetic hydrotalcite on acute gastric or intestinal lesion formation in rats and dogs

  • Original Articles
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Cholestyramine, a bile-binding agent, markedly inhibited the development of gastric lesions induced by water-immersion stress in rats and of gastric and intestinal lesions induced by indomethacin in rats and dogs with an intact pylorus. However, cholestyramine had no effect on gastric lesions induced by stress in pylorus-ligated rats and on aspirin-induced gastric lesions in rats and dogs with or without pylorus ligation. Hydrotalcite, a potent antacid, significantly inhibited the gastric lesions induced by stress and aspirin in rats and dogs with or without pylorus ligation. Hydrotalcite also inhibited the gastric lesions induced by a single administration of indomethacin in rats with an intact pylorus. In contrast, the agent had no effect on gastric and intestinal lesions induced by repeated administration of indomethacin to rats and dogs with an intact pylorus. These results suggest that while bile probably plays an important role in the pathogenesis of stress-induced gastric lesions and of indomethacin-induced gastric and intestinal lesions, bile does not appear to play a role in the pathogenesis of aspirin-induced gastric lesions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. du Plessis DJ: Pathogenesis of gastric ulceration. Lancet 1:974–978, 1965

    Google Scholar 

  2. Rhodes J, Barnardo DE, Phillips, SF, Rovelstad RA, Hofmann AF: Increased reflux of bile into the stomach in patients with gastric ulcer. Gastroenterology 57:241–252, 1969

    Google Scholar 

  3. Capper WM, Airth GR, Kilby JO: A test for pylorus regurgitation. Lancet 2:621–623, 1966

    Google Scholar 

  4. Davenport HW: Destruction of the gastric mucosal barrier by detergents and urea. Gastroenterology 54:175–181, 1968

    Google Scholar 

  5. Ivey KJ, DenBesten L, Clifton JA: Effect of bile salts on ionic movement across the human gastric mucosa. Gastroenterology 59:683–690, 1970

    Google Scholar 

  6. Black RB, Hole D, Rhodes J: Bile damage to the gastric mucosal barrier: The influence of pH and bile acid concentration. Gastroenterology 61:178–184, 1971

    Google Scholar 

  7. Hamza KN, DenBesten L: Bile salts producing stress ulcers during experimental shock. Surgery 71:161–167, 1972

    Google Scholar 

  8. Braun SA, Samson RH, Norton L, Eiseman B: Bile reflux in experimental stress ulcer. Surgery 71:521–524, 1973

    Google Scholar 

  9. Mersereau WA, Hinchey EJ: Prevention of bile reflux-induced acute gastric ulceration in the rat by cholestyramine. Ann Surg 179:883–888, 1974

    Google Scholar 

  10. Mann NS: Bile-induced acute erosive gastritis. Its prevention by antacid, cholestyramine, and prostaglandin E2. Am J Dig Dis 21:89–92, 1976

    Google Scholar 

  11. Schumpelick V, Grossner D: Cholestyramine zur Stressulcus-Prophylaxe der Ratte. Res Exp Med 166:235–239, 1975

    Google Scholar 

  12. Zike WL, Safaie-Shirazi S, Paluska G, DenBesten L: The role of cholestyramine in the prevention of stress ulcers. Gastroenterology 64:826, 1973

    Google Scholar 

  13. Ritchie WP, Shearburn EW: Influence of isoproterenol and cholestyramine on acute gastric mucosal ulcerogenesis. Gastroenterology 73:62–65, 1977

    Google Scholar 

  14. Norton L, Mathews D, Avrum L, Eiseman B: Pharmacological protection against swine stress ulcer. Gastroenterology 66:503–508, 1974

    Google Scholar 

  15. Clain JE, Malagelada JR, Chadwick VS, Hofmann AF: Binding properties in vitro of antacids for conjugated bile acids. Gastroenterology 73:556–559, 1977

    Google Scholar 

  16. Playle AC, Gunning SR, Llewellyn AF: Thein vivo antacid and anti-pepsin activity of hydrotalcite. Pharm Acta Helv 49:298–302, 1974

    Google Scholar 

  17. Mendelsohn D, Mendelsohn L: Hydrogen ion, pepsin and bile acid binding properties of hydrotalcite. S. Afr Med J 49:1011–1014, 1975

    Google Scholar 

  18. Takagi K, Okabe S: The effects of drugs on the production and recovery processes of the stress ulcer. Jpn J Pharmacol 18:9–18, 1968

    Google Scholar 

  19. Takeuchi K, Okabe S, Takagi K: A new model of stress ulcer in the rat with pylorus ligation and its pathogenesis. Am J Dig Dis 21:782–788, 1976

    Google Scholar 

  20. Okabe S, Takeuchi K, Nakamura K, Takagi K: Pathogenesis of gastric lesions induced by aspirin in the pylorus-ligated rat. Jpn J Pharmacol 24:363–371, 1974

    Google Scholar 

  21. Hung CR, Takeuchi K, Okabe S, Murata T, Takagi K: Effects ofl-glutamine on acetylsalicylic acid induced gastric lesions and acid back diffusion in dogs. Jpn J Pharmacol 26:703–709, 1976

    Google Scholar 

  22. Tabata K, Okabe S: Effects of 16, 16-dimethyl prostaglandin E2 methyl ester on aspirin- and indomethacin-induced gastrointestinal lesions in dogs. Dig Dis Sci 25:439–448, 1980.

    Google Scholar 

  23. Anson ML: The estimation of pepsin, trypsin, papain and cathepepsin with hemoglobin. J Gen Physiol 22:79–89, 1938

    Google Scholar 

  24. Okabe S, Hung CR, Takeuchi K, Takago K: Effects ofl-glutamine on acetylsalicylic acid or taurocholic acid-induced gastric lesions and secretory changes in pylorus-ligated rats under normal or stress conditions. Jpn J Pharmacol 26:455–460, 1976

    Google Scholar 

  25. Hemmati M, Abtahi F, Farrokhsiar M, Djahanguiri B: Prevention of restraint and indomethacin-induced gastric ulceration by bile duct or pylorus ligation in rats. Digestion 10:108–112, 1974

    Google Scholar 

  26. Kitagawa H, Fujiwara M, Osumi Y: Effects of waterimmersion stress on gastric secretion and mucosal blood flow in rats. Gastroenterology 77:298–302, 1979

    Google Scholar 

  27. Okabe H, Takeuchi K, Urushidani T, Takagi K: Effects of cimetidine, a histamine H2-receptor antogonist, on various experimental gastric and duodenal ulcers. Am J Dig Dis 22:677–684, 1977

    Google Scholar 

  28. Lee YH, Mollison KW, Cheng WD: The effects of anti-ulcer agents on indomethacin-induced gastric ulceration in the rat. Arch Int Pharmacol Ther 192:370–377, 1971

    Google Scholar 

  29. Kasuya Y, Urushidani T, Okabe S: Effects of various drugs and vagotomy on indomethacin-induced gastric ulcers in the rat. Jpn J Pharmacol 29:670–673, 1979

    Google Scholar 

  30. Wax J, Clinger WA, Varner P, Bass P, Winder CV: Relationship of the enterohepatic cycle to ulcerogenesis in the rat small bowel with flufenamic acid. Gastroenterology 58:772–780, 1970

    Google Scholar 

  31. Takemoto K, Tanaka K: Inhibitory effect of cholestyramine on the intestinal ulcer formation in rats given an antiphlogistic agent. Gastroenterology 67:765–766, 1974

    Google Scholar 

  32. Brodie DA, Cook PG, Bauer BJ, Dagle GE: Indomethacin-induced intestinal lesions in the rat. Toxicol Appl Pharmacol 17:615–624, 1970

    Google Scholar 

  33. Gallo DG, Bailey KR, Sheffner AL: The interaction between cholestyramine and drugs. Proc Soc Exp Biol Med 120:60–65, 1965

    Google Scholar 

  34. Hucker HB, Zacchei AG, Cox SV, Brodie DA, Cantwell NHR: Studies on the absorption, distribution and excretion of indomethacin in various species. J Pharmacol Exp Ther 153:237–249, 1966

    Google Scholar 

  35. Guth PH, Paulsen G, Lynn D, Aures D: Mechanism of prevention of aspirin-induced gastric lesions by bile duct ligation in the rat. Gastroenterology 71:750–753, 1976

    Google Scholar 

  36. Davenport HW: Salicylate damage to the gastric mucosal barrier. N Engl J Med 276:1307–1312, 1967

    Google Scholar 

  37. Gottschalk A, Menguy R: Role of gastric acid in aspirin-induced erosive gastritis. Proc Soc Exp Biol Med 135:384–388, 1970

    Google Scholar 

  38. Brodie DA, Chase BJ: Role of gastric acid in aspirin-induced gastric irritation in the rat. Gastroenterology 53:604–610, 1967

    Google Scholar 

  39. Eder HA: Drugs used in the prevention and treatment of atherosclerosis.In The Pharmacological Basis of Therapeutics. Goodman LS, Gilman A (eds.). New York, Macmillan, 1975, pp 748–749

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Applied Pharmacology, Kyoto College of Pharmacy, Misasagi, Yamashina, Kyoto 607, Japan

    Yasunobu Ishihara MA &  Susumu Okabe PhD

Authors
  1. Yasunobu Ishihara MA
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susumu Okabe PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ishihara, Y., Okabe, S. Effects of cholestyramine and synthetic hydrotalcite on acute gastric or intestinal lesion formation in rats and dogs. Digest Dis Sci 26, 553–560 (1981). https://doi.org/10.1007/BF01308106

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01308106

Keywords

Search

Navigation