Skip to main content

Mepirizole-induced duodenal ulcers in rats and their pathogenesis

Abstract

Duodenal ulcers were produced in rats following either an oral or parenteral administration of 200 mg/kg of mepirizole, a nonsteroidal antiinflammatory agent. Deep ulcers, including perforated ones, were induced in the proximal duodenum with an incidence of over 90%. Mortality due to perforation was less than 5%. The agent also induced several erosions in the antrum. Feeding of animals after the ingestion of mepirizole markedly suppressed the development of both duodenal ulcers and gastric erosions. Antacids, anticholinergic agents, a histamine H2-receptor antagonist and 16-DMPGE2 dosedependently inhibited mepirizole-induced duodenal ulcers. Gastric erosions were also significantly inhibited by antacids and anticholinergic agents but not by a histamine H2-receptor antagonist and 16-DMPGE2. Intraduodenally administered mepirizole dosedependently inhibited the gastric secretion in pylorus-ligated rats. This ulcer model should be useful for screening antiulcer agents and for the study of pathogenesis of duodenal ulcers and gastric erosions.

This is a preview of subscription content, access via your institution.

References

  1. Robert A, Stout TJ, Dale JE: Production by secretagogues of duodenal ulcers in the rat. Gastroenterology 59:95–102, 1970

    Google Scholar 

  2. Szabo S, Selye H: Duodenal ulcers produced by propionitrile in rats. Arch Pathol 93:390–391, 1972

    Google Scholar 

  3. Selye H, Szabo S: An experimental model for the production of perforating duodenal ulcers by cysteamine in the rat. Nature 244:458–459, 1973

    Google Scholar 

  4. Akimoto T, Tsukada K, Yamasaki T, Kojima H, Kasahara A, Akashi A, Yamaguchi K, Ohshima Y: Pharmacological studies of an antiinflammatory agent 1-(4-methoxy-6 methyl-2-pyrimidinyl)-3-methyl-5-methoxypyrazole (DA-398). Folia Pharmcol Jpn 65:378–409, 1969

    Google Scholar 

  5. Tsurumi K, Nosaki M, Hiramatsu Y, Hayashi M, Fujimura H: Pharmacological studies of 1-(4-methyl-6-methoxy-2-pyrimidinyl)-3-methyl-5-methoxypyrazole. Folia Pharmacol Jpn 65:620–642, 1969

    Google Scholar 

  6. Tanaka H, Shuto K, Marumo H: Effect ofN-acetyl-l-glutamine aluminum complex (KW-110) on experimental duodenal ulcers in rats. Pharmacometrics 20:185–193, 1980

    Google Scholar 

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

    Google Scholar 

  8. Robert A, Dale JE: Prevention of duodenal ulcers in rats by feeding. Proc Soc Exp Biol Med 136:439–440, 1971

    Google Scholar 

  9. Szabo S, Haith LR, Reynolds S: Pathogenesis of duodenal ulceration produced by cysteamine or propionitrile. Am J Dig Dis 24:471–477, 1979

    Google Scholar 

  10. Okabe S, Kunimi H, Ohtsuki H: Effects of a new histamine H2-receptor antagonist, ranitidine, on experimental acute gastric and duodenal ulcers. Folia Pharmacol Jpn 77:397–406, 1981

    Google Scholar 

  11. Whittle BJR: Relationship between the prevention of rat gastric erosions and the inhibition of acid secretion by prostaglandins. Eur J Pharmacol 40:233–239, 1976

    Google Scholar 

  12. Kauffman GL, Grossman MI: Prostaglandin and cimetidine inhibit the formation of ulcers produced by parenteral salicylates. Gastroenterology 75:1099–1102, 1978

    Google Scholar 

  13. Robert A, Schultz JR, Nezamis JE, Lancaster C: Gastric antisecretory and antiulcer properties of PGE2, 15-methyl PGE2 and 16, 16-dimethyl PGE2. Intravenous, oral and intrajejunal administration. Gastroenterology 70:359–370, 1976

    Google Scholar 

  14. Robert A, Nezamis JE, Dale JE, Stowe DE: Role of gastric acid in the development of duodenal ulcers in the rat. Digestion 6:35–45, 1972

    Google Scholar 

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

    Google Scholar 

  16. Robert A, Nezamis JE, Lancaster C, Badalamenti JN: Cysteamine-induced duodenal, ulcers: A new model to test antiulcer agents. Digestion 11:199–214, 1974

    Google Scholar 

  17. Groves WG, Schlosser JH, Mead FD: Acid hypersecretion and duodenal ulcers produced by cysteamine in rats. Res Commun Chem Pathol Pharmacol 9:523–534, 1974

    Google Scholar 

  18. Ishii Y, Fujii Y, Homma M: Gastric acid stimulating action of cysteamine in the rat. Eur J Pharmacol 36:331–336, 1976

    Google Scholar 

  19. Tamaki H, Onoda Y, Kashida T: Gastric secretion and duodenal ulcer formation induced by cysteamine in rats. Jpn J Pharmacol 28:647–649, 1978

    Google Scholar 

  20. Fujii Y, Ishii Y: Influence of various factors and drugs on cysteamine-induced duodenal ulcers in the rat. Jpn J Pharmacol 25:663–670, 1975

    Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Okabe, S., Ishihara, Y., Inoo, H. et al. Mepirizole-induced duodenal ulcers in rats and their pathogenesis. Digest Dis Sci 27, 242–249 (1982). https://doi.org/10.1007/BF01296923

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01296923

Keywords

  • Public Health
  • Histamine
  • Perforation
  • Duodenal Ulcer
  • Antiinflammatory Agent