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Relationship between Drug Absorption, Inhibition of Cyclooxygenase and Lipoxygenase Pathways, and Development of Gastric Mucosal Damage by Nonsteroidal Antiinflammatory Drugs in Rats and Pigs

  • K. D. Rainsford
  • Sheila A. Fox
  • D. J. Osborne
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

Many authors have provided evidence for an association between inhibition of prostaglandin (PG) synthesis by the nonsteroidal and antiinflammatory (NSAI) drugs and their propensity to elicit gastric mucosal damage (Boughton-Smith and Whittle, 1983; Peskar et al., 1981, 1984; Rainsford and Willis, 1982; Rainsford, 1984; Rainsford et al., 1984). By comparison, relatively little is known about the relationship between the inhibition by NSAI drugs of the synthesis of various eicosanoids to (1) the time-dependent changes induced in the various mucosal cells by these drugs and (2) the pattern of drug uptake into the gastric mucosa. Furthermore, it is not known if the different NSAI drugs with varying potency as PG synthesis inhibitors have the capacity to elicit damage to the mucosal cells in the same way. These aspects are important in order to determine the precise role that inhibition of the synthesis of the different eicosanoids has in the induction of pathological changes in different cells by ulcerogenic NSAI drugs. The studies reported here are an attempt to provide some information in answer to these questions.

Keywords

Gastric Mucosa Parietal Cell Mucosal Cell Inhibit Platelet Aggregation Prostaglandin Production 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Boughton-Smith, N.K., and Whittle, B.J.R., 1983, Stimulation and inhibition of prostacyclin formation in the gastric mucosa and ileum in vitro by anti-inflammatory agents, Br. J. Pharmacol. 78:173–180.PubMedCrossRefGoogle Scholar
  2. Brune, K., Rainsford, K.D., Wagner, K., and Peskar, B.A., 1981, Inhibition by anti-inflammatory drugs of prostaglandin production in cultured macrophages. Factors influencing the apparent drug effects, Naunyn Schmiedebergs Arch. Pharmacol. 315:269–276.PubMedCrossRefGoogle Scholar
  3. Harding, R. K., and Morris, G. P., 1976, Pathological effects of aspirin and of haemorrhagic shock on the gastric mucosa of the rat, in: Scanning Electron Microscopy/1976, Part V, Proceedings of the Workshop on Advances in Biomedical Applications of the SEM, ITT Research Institute, Chicago, pp. 253-262.Google Scholar
  4. Peskar, B. A., Anhut, H., Kroner, E. E., and Peskar, B. M., 1978, Development, specificity and some applications of radioimmunoassays for prostaglandins and related compounds, in: Advances in Pharmacology and Therapeutics, Vol. 7, Biochemical Clinical Pharmacology (J. P. Tillement, ed.), Pergamon Press, Oxford, pp. 278-286.Google Scholar
  5. Peskar, B.M., Rainsford, K.D., Brune, K., and Gerok, K., 1981, Effekt nichsteroidartiger Antiphlogistika auf Plasma-und Magenmukosakonzentrationen von Prostaglandinen, Verh. Deut. Ges. Inn. Med.Verh. Deut. Ges. Inn. Med. 87:833–838.Google Scholar
  6. Peskar, B. M., Weiler, H., and Meyer, C., 1984, Inhibition of prostaglandin production in the gastrointestinal tract by antiinflammatory drugs, in: Side-Effects of Anti-Inflammatory/Analgesic Drugs (K. D. Rainsford and G. P. Velo, eds.), Raven Press, New York, pp. 39-50.Google Scholar
  7. Rainsford, K.D., 1975, Electron microscopic observations on the effects of orally-administered aspirin and aspirin-bicarbonate mixtures on the development of gastric mucosal damage in the rat, Gut 16:514–527.PubMedCrossRefGoogle Scholar
  8. Rainsford, K. D., 1981, Comparison of the gastric ulcerogenic activity of new non-steroidal antiinflammatory drugs in stressed rats, Br. J. Pharmacol. 73:226P–227P.Google Scholar
  9. Rainsford, K. D., 1984, Mechanisms of gastrointestinal ulceration by nonsteroidal anti-inflammatory/analgesic drugs, in: Side-effects of Anti-Inflammatory/Analgesic Drugs (K. D. Rainsford and G. P. Velo, eds.), Raven Press, New York, pp. 51-64.Google Scholar
  10. Rainsford, K.D., and Willis, C., 1982, Relationship of gastric mucosal damage induced in pigs by anti-inflammatory drugs to their effects on prostaglandin production, Dig. Dis. Sci. 27:624–635.PubMedCrossRefGoogle Scholar
  11. Rainsford, K. D., Fox, S. A., and Osborne, D. J., 1984, Comparative effects of some non-steroidal anti-inflammatory drugs on the ultrastructural integrity and prostaglandin levels in the rat gastric mucosa: Relationship to drug uptake, Scand. J. Gastroenterol. 19(Suppl. 101):55–68.Google Scholar
  12. Robins, P.G., 1981, Ultrastructural observations on the pathogenesis of aspirin-induced gastric erosions, Br. J. Exp. Pathol. 61:497–504.Google Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • K. D. Rainsford
    • 1
  • Sheila A. Fox
    • 1
  • D. J. Osborne
    • 2
  1. 1.Pharmacology DepartmentUniversity of CambridgeCambridgeUK
  2. 2.Lilly Research CentreErl Wood ManorWindleshamUK

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