Cytoprotection Historical Perspective

  • André Robert


Traditionally, the aim of antiulcer therapy has been either to inhibit secretion of gastric acid by parietal cells or neutralize acid that has already been secreted. To this effect, the use of antacids has been, and continues to be, an effective form of treatment, especially for duodenal ulcer. Anticholinergic agents, by inhibiting the action of acetylcholine (ACh), had been used until the mid-1970s, although the occurrence of side effects always prevented administration of adequate doses. The advent of histamine H2-antagonists, first metiamide, and later cimetidine, ranitidine, and famotidine, led to the administration of strongly antisecretory doses with only minimal side effects and accelerated the healing of peptic ulcer. More recently, omeprazole, a substituted benzimidazole that inhibits (H+-K+)-ATPase within the parietal cell canaliculi, was shown to inhibit acid secretion totally and to induce duodenal ulcer healing in 2 weeks.


Gastric Mucosa Acid Secretion Intestinal Lesion Gastric Mucosal Injury Gastric Mucosal Cell 
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Annotated Bibliography

  1. Guth PH, Paulsen G, Nagata H: Histologic and microcirculatory changes in alcohol-induced gastric lesions in the rat: Effect of prostaglandin cytoprotection. Gastroenterology 87: 1083–1090, 1984. These studies show that cytoprotective prostaglandins maintain the microcirculation of the gastric mucosa, even after exposure to ethanol.PubMedGoogle Scholar
  2. Lacy ER, Ito S: Microscopic analysis of ethanol damage to rat gastric mucosa after treatment with a prostaglandin, Gastroenterology 83:619–625, 1982. Prostaglandin protects the gastric mucosa from necrosis after exposure to ethanol, while the surface epithelium is not protected; rapid mucosal restitution by cell migration is described.PubMedGoogle Scholar
  3. Robert A: Antisecretory, antiulcer, cytoprotective, and diarrheogenic properties of prostaglandins. Adv Prostaglandins Thromboxane Res 507-520, 1976. This is the first report on the gastric and intestinal cytoprotective effect of prostaglandins.Google Scholar
  4. Robert A: Cytoprotection by prostaglandins. Gastroenterology 77:761–67, 1979. This paper reviews the various types of cytoprotection, gastric and intestinal.PubMedGoogle Scholar
  5. Robert A, Nezamis JE, Lancaster C, et al: Mild irritants prevent gastric necrosis through “adaptive cytoprotection” mediated by prostaglandins. Am J Physiol 245:G113–121, 1983. These studies show that adaptive cytoprotection can be produced by mild irritants, via stimulation of endogenous formation of prostaglandins by the stomach.PubMedGoogle Scholar
  6. Schmidt KL, Henagan JM, Hilburn PJ, et al: Prostaglandin cytoprotection against ethanol-induced gastric injury in the rat: A histologic and cytologie study of the surface epithelium. Gastroenterology 88:649–659, 1985. This light and electron microscopic study describes gastric mucosal lesions produced by ethanol, as well as the extent of protection by a prostaglandin.PubMedGoogle Scholar
  7. Szabo S, Trier JS, Frankel PW: Sulfhydryl compounds may mediate gastric cytoprotection. Science 214:200–202, 1981. This article presents studies on the role of sulfhydryl compounds in the mechanism of gastric cytoprotection.PubMedCrossRefGoogle Scholar
  8. Tarnawski A, Hollander D, Stachura J, et al: Prostaglandin protection of the gastric mucosa against alcohol injury — A dynamic time-related process. Role of the mucosal proliferative zone. Gastroenterology 88:344–352, 1985. This article describes a light and electron microscopic study of gastric mucosal cytoprotection by a prostaglandin in function of time, showing that the mucosal proliferative zone is protected.Google Scholar
  9. Terano A, Mach T, Stachura J, et al: Effect of 16, 16-dimethyl prostaglandin E2 on aspirin-induced damage to gastric epithelial cells in tissue culture. Gut 25:19–25, 1984. This study shows that a prostaglandin applied in vitro to cultured gastric cells reduces damage produced by aspirin.PubMedCrossRefGoogle Scholar
  10. Whittle BJR, Steel G: Evaluation of the protection of rat gastric mucosa by a prostaglandin analogue using cellular enzyme marker and histologic techniques. Gastroenterology 88:315–327, 1984. A cytoprotective prostaglandin protects gastric mucosal cells against ethanol, as shown by the prevention of release of cellular enzymes and by histology.Google Scholar

Copyright information

© Plenum Publishing Corporation 1989

Authors and Affiliations

  • André Robert
    • 1
  1. 1.Drug Metabolism ResearchThe Upjohn CompanyKalamazooUSA

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