Skip to main content
Log in

Effect of sucralfate and its components on taurocholate-induced damage to rat gastric mucosal cells in tissue culture

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

Abstract

The present study evaluated the effect of sucralfate and its components, sucrose octasulfate and aluminum hydroxide, on: (1) damage to rat cultured gastric mucosal cells induced by sodium taurocholate in a neutral environment and in conditions independent of systemic factors, (2) prostaglandin E2 and on 6-keto prostaglandinF release by cultured cells, and (3) sulfhydryl content of cultured cells. Cell damage was quantitated by chromium-51 release assay. Prostaglandin E2 and 6-keto prostaglandinF were measured by radioimmunoassay. Total sulfhydryl content of cultured cells was determined calorimetrically. Microscopically, sucralfate was found to adhere tightly to epithelial cell surfaces despite frequent washings. Sucralfate 2 mg/ml and 5 mg/ml significantly decreased taurocholate-induced damage, reducing taurocholate-induced specific51Cr release by 11.8 points (equal to 29% decrease in cell damage, (P< 0.01) and 22.9 points (equal to 56% decrease in cell damage, (P<0.001), respectively. Sucrose octasulfate and aluminum hydroxide did not exert significant protection against damage induced by sodium taurocholate. The protective effect of sucralfate was not prevented by indomethacin, nor was it counteracted by the sulfhydryl blocker, iodoacetamide. Sucralfate, but not its components, significantly and dose-dependently stimulated prostaglandin E2 (r=0.94, P<0.05 and 6-keto prostaglandinF (r=0.89, P<0.05) production by cultured cells. Neither sucralfate nor its components affected sulfhydryl content of cultured cells. In conclusion, sucralfate, but not its components, (1) protects rat gastric mucosal cells against taurocholate-induced damage in conditions independent of systemic factors and in a neutral environment and (2) significantly stimulates prostaglandin production by cultured cells. (3) The protection by sucralfatein vitro does not seem to depend on its stimulatory effect on endogenous prostaglandin synthesis.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Hollander D: Sucralfate: New agent for treatment of duodenal ulcer.In Duodenal Ulcer, Gastric ulcer: Sucralfate. A New Therapeutic Concept. WF Caspary (ed). Baltimore, Urban & Schwarzenberg, 1981, pp 49–53

    Google Scholar 

  2. Hollander D: Efficacy of sucralfate for duodenal ulcers: A multicenter, double blind trial. J Clin Gastroenterol 3(suppl 2):153–157, 1981

    Google Scholar 

  3. McHardy GG: A multicenter, double-blind trial of sucralfate and placebo in duodenal ulcer. J Clin Gastroenterol 3(suppl 2):147–152, 1981

    Google Scholar 

  4. Okabe S, Takeuchi K, Kunimi H, Kanno M, Kawashima M: Effects of an antiulcer drug, sucralfate (a basic aluminum salt of sulfated disaccharide), on experimental gastric lesions and gastric secretion in rats. Dig Dis Sci 28:1034–1042, 1983

    PubMed  Google Scholar 

  5. Harrington SJJ, Schlegel JF, Code CF: The protective effect of sucralfate on the gastric mucosa of rats. J Clin Gastroenterol 3(suppl 2):129–134, 1981

    Google Scholar 

  6. Hollander D, Tarnawski A, Gergely H, Zipser RD: Sucralfate protection of the gastric mucosa against ethanol-induced injury: A prostaglandin mediated process? Scand J Gastroenterol 19(suppl 101):97–102, 1984

    PubMed  Google Scholar 

  7. Tarnawski A, Hollander D, Gergely H, Stachura J: Comparison of antacid sucralfate, cimetidine and ranitidine in protection of gastric mucosa against ethanol injury. Am J Med 79:19–23, 1985

    Google Scholar 

  8. Hollander D, Tarnawski A, Krause W, Gergely H: Protective effect of sucralfate against alcohol-induced gastric mucosal injury in the rat. Macroscopic, histologic, ultrastructural, and functional time sequence analysis. Gastroenterology 88:366–374, 1985

    PubMed  Google Scholar 

  9. Bighley D, Giesing D: Mechanism of action studies of sucralfate.In Duodenal Ulcer, Gastric Ulcer: Sucralfate. A New Therapeutic Concept. WF Caspary (ed). Baltimore, Urban & Schwarzenberg, 1981, pp 3–12

    Google Scholar 

  10. Nagashima R: Mechanism of action of sucralfate. J Clin Gastroenterol 3(suppl 2):117–127, 1981

    PubMed  Google Scholar 

  11. McGraw BF, Caldwell EG: Sucralfate. Drug Intell Clin Pharm 15:578–580, 1981

    PubMed  Google Scholar 

  12. Tarnawski A, Hollander D, Krause WJ, Zipser RD, Stachura J, Gergely H: Does sucralfate affect the normal gastric mucosa? Histologic, ultrastructural, and functional assessment in the rat. Gastroenterology 90:893–905, 1986

    PubMed  Google Scholar 

  13. Ligumski M, Karmely F, Rachmilewitz D: Sucralfate protection against gastrointestinal damage: Possible role of prostanoids. Isr J Med Sci 22:801–806, 1986

    PubMed  Google Scholar 

  14. Shea-Donohue T, Steel L, Montcalm E, Dubois A: Gastric protection by sucralfate. Role of mucus and prostaglandins. Gastroenterology 91:660–666, 1986

    PubMed  Google Scholar 

  15. Yoshida T, Terao N, Nagashima R: Sucralfate, a basic aluminum salt of sucrose octasulfate: IV interaction with enzyme pepsin. Arzneim Forsch 30:78–80, 1980

    Google Scholar 

  16. Samloff IM, O'Dell C: Inhibition of peptic activity by sucralfate. Am J Med 79(suppl 2C):15–18, 1985

    PubMed  Google Scholar 

  17. Caspary WF: Binding von Gallensauren an Sucralfat und Cholestyramin.In Sucralfat, Eine Neue Therapeutische Konzeption. WF Caspary (ed). Munich, Urban & Schwarzenberg, 1978, pp 32–28

    Google Scholar 

  18. Graham DY, Sackman JW, Gicsing DH, Runser DJ:In vitro adsorption of bile salts and aspirin to sucralfate. Dig Dis Sci 29:402–406, 1984

    PubMed  Google Scholar 

  19. Nagashima R: Development and characteristics of sucralfate. J Clin Gastroenterol 3(suppl 2):103–110, 1981

    PubMed  Google Scholar 

  20. Szabo S, Trier JS, Frankel PW: Sulfhydryl compounds may mediate gastric cytoprotection. Science 214:200–202, 1981

    PubMed  Google Scholar 

  21. Terano A, Ivey KJ, Stachura J, Sekhon S, Hosojima H, McKenzie WN Jr, Krause WJ, Wyche JH: Cell culture of rat gastric fundic mucosa. Gastroenterology 83:1280–1291, 1982

    PubMed  Google Scholar 

  22. Wigzell H: Quantitative titrations of mouse H-2 antibodies using51Cr labelled target cells. Transplantation 3:423–431, 1975

    Google Scholar 

  23. Romano M, Razandi M, Sekhon S, Krause WJ, Ivey KJ: Human cell line for study of damage to gastric epithelial cells in vitro. J Lab Clin Med 111:430–440, 1988

    PubMed  Google Scholar 

  24. Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254, 1976

    PubMed  Google Scholar 

  25. Harlan JM, Levine JD, Callahan KS, Schwartz BR, Harker LA: Glutathione redox cycle protects cultured endothelial cells against lysis by extracellularly generated hydrogen peroxide. J Clin Invest 73:706–713, 1984

    PubMed  Google Scholar 

  26. Hiraishi H, Terano A, Ota S, Ivey KJ, Sugimoto T: Oxygen reactive metabolite-induced cytotoxicity to cultured rat gastric mucosal cells. Am J Physiol 253:G40-G48, 1987

    PubMed  Google Scholar 

  27. Beutler E, Duron O, Kelly BM: Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888, 1963

    PubMed  Google Scholar 

  28. Duncan DB: Multiple range and multiple F tests. Biometrics 11:1–42, 1955

    Google Scholar 

  29. Hiraishi H, Terano A, Ota S, Shia J, Kobayashi T, Harada H, Ishii M, Ivey KJ, Sugimoto T: Prostaglandin production in cultured gastric mucosal cells: Role of cAMP on its modulation. Prostaglandins 32:259–273, 1986

    PubMed  Google Scholar 

  30. Romano M, Razandi M, Ivey KJ: Somatostatin stimulates prostaglandin production by rat gastric epithelial cellsin vitro, but is not cytoprotective. Dig Dis Sci 33:1435–1440, 1988

    PubMed  Google Scholar 

  31. Allen A, Garner A: Mucus and bicarbonate secretion in the stomach and their possible role in mucosal protection. Gut 21:249–262, 1980

    PubMed  Google Scholar 

  32. Morris GP, Keenan CM, MacNaughton WK, Wallace JL, Williamson TE: Protection of rat gastric mucosa by sucralfate. Effects of luminal stasis and of inhibition of prostaglandin synthesis. Am J Med 86(suppl 6A):10–16, 1989

    PubMed  Google Scholar 

  33. Shorrock CJ, Rees WDW: Effect of sucralfate on human gastric bicarbonate secretion and local prostaglandin E2 metabolism. Am J Med 86(suppl 6A):2–4, 1989

    Google Scholar 

  34. Szabo S, Hollander D: Pathways of gastrointestinal protection and repair: Mechanisms of action of sucralfate. Am J Med 86(suppl 6A):23–31, 1989

    Google Scholar 

  35. Nagashima R, Hirano T: Selective binding of sucralfate to ulcer lesions. I. Experiments in rats with acetic acidinduced gastric ulcer receiving unlabelled sucralfate. Arzneim Forsch 30:80–83, 1980

    Google Scholar 

  36. Steiner K, Garbe A: Specific binding of14C-sucralfate to acetic acid-induced gastric and duodenal ulcers of the rat.In Duodenal Ulcer, Gastric Ulcer: Sucralfate. A New Therapeutic Concept. W Caspary, (ed). Baltimore, Urban & Schwarzenberg, 1981, pp 93–100

    Google Scholar 

  37. Nakazawa S, Nagashima R, Samloff IM: Selective binding of sucralfate to gastric ulcer in man. Dig Dis Sci 26:297–300, 1981

    PubMed  Google Scholar 

  38. Konturek SJ, Kwiecien N, Obtulowicz W, Olesky J: Gastroprotection by sucralfate against acetylsalicylic acid in humans. Role of endogenous prostaglandins. Scand J Gastroenterol 22(suppl 140):19–22, 1987

    Google Scholar 

  39. Robert A, Eberle D, Kaplowitz N: Role of glutathione in gastric mucosal cytoprotection. Am J Physiol 247:G296-G304, 1984

    PubMed  Google Scholar 

  40. Szabo S, Brown A. Prevention of ethanol-induced vascular injury and gastric mucosal lesions by sucralfate and its components. Proc Soc Exp Biol 185:493–497, 1987

    Google Scholar 

  41. Ota S, Razandi M, Sekhon S, Terano A, Hiraishi H, Ivey KJ: Cytoprotective effect of acetaminophen against taurocholate-induced damage to rat gastric monolayer cultures. Dig Dis Sci 33:938–994, 1988

    PubMed  Google Scholar 

  42. Danesh BJZ, Duncan A, Russel RI, Mitchell G. Effect of intragastric pH on mucosal protective action of sucralfate. Gut 29:1379–1385, 1988

    PubMed  Google Scholar 

  43. Romano M, Razandi M, Raza A, Szabo S, Ivey KJ: Protection of human gastric epithelial cellsin vitro by the sulfhydryl agent cysteamine is not related to stimulation of prostaglandin synthesis. Gastroenterology 92:1600, 1987

    Google Scholar 

  44. Terano A, Ota S, Mach T, Hiraishi H, Stachura J, Tarnawski A, Ivey KJ: Prostaglandin protects against taurocholateinduced damage to rat gastric mucosal cell culture. Gastroenterology 92:669–677, 1987

    PubMed  Google Scholar 

  45. Chen MC, Sanders MJ, Amirian DA, Thomas LP, Kauffman G, Soll AH: Prostaglandin E2 production by dispersed canine fundic mucosal cells: contribution of macrophages and endothelial cells as major sources. J Clin Invest 84:1536–1549, 1989

    PubMed  Google Scholar 

  46. Szelenyi L, Postius S, Engler H: Evidence for a functional cytoprotective effect produced by antacids in the rat stomach. Eur J Pharmacol 88:403–406, 1983

    PubMed  Google Scholar 

  47. Keenan CM, Morris GP: Protection of the rat gastric mucosa by sucralfate is dependent on the presence of an adherent coat. Gastroenterology 92:1462, 1987 (abstract)

    Google Scholar 

  48. Szelenyi I, Brune K. Possible role of sulfhydryls in mucosal protection induced by aluminum hydroxide. Dig Dis Sci 31:1207–1210, 1986

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Dr. Romano was a visiting scientist from Istituto di Medicina Generale e Metodologia clinica, 1st School of Medicine, University of Naples, Italy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Romano, M., Razandi, M. & Ivey, K.J. Effect of sucralfate and its components on taurocholate-induced damage to rat gastric mucosal cells in tissue culture. Digest Dis Sci 35, 467–476 (1990). https://doi.org/10.1007/BF01536921

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01536921

Key words

Navigation