Advertisement

Agents and Actions

, Volume 21, Issue 3–4, pp 316–319 | Cite as

The effects of 5-lipoxygenase inhibitors and leukotriene antagonists on the development of gastric lesions induced by nonsteroidal antiinflammatory drugs in mice

  • K. D. Rainsford
Ulcerogenicity

Conclusions

The findings presented in this report show that: (1) 5-lipoxygenase inhibitors and some leukotriene antagonists protect the gastric mucosa against lesions induced by oral or parenteral administration of most NSAIDs, with the possibility of some variation in effects with aspirin.

(2) These observations suggest that overproduction of leukotrienes and other products of 5-lipoxygenase activity may play a role in the development of acute gastric mucosal damage induced by NSAIDs.

Keywords

Aspirin Antiinflammatory Drug Nonsteroidal Antiinflammatory Drug Gastric Mucosa Mucosal Damage 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [1]
    B. J. R. Whittle,Arachidonic acid metabolites and the gastrointestinal toxicity of antiinflammatory agents. Prostaglandins21, (Suppl.), 113–118 (1981).CrossRefGoogle Scholar
  2. [2]
    K. D. Rainsford,Mechanisms of gastric contrasted with intestinal damage by nonsteroidal antiinflammatory drugs. In:Side Effects of Antiinflammatory Drugs. Vol. II (Eds.: K. D. Rainsford and G. P. Velo) pp. 3–26. MIP Press, Lancaster 1987.Google Scholar
  3. [3]
    J. R. Walker and J. Harvey,Actions of antiinflammatory drugs on leukotriene and prostaglandin metabolism: relationships to asthma and other hypersensitivity reactions. Inside effects of antiinflammatory/analgesic drugs. (Eds. K. D. Rainsford and G. P. Velo) pp. 227–238 Raven Press, New York 1984.Google Scholar
  4. [4]
    R. G. Pendleton and J. R. Stavorski,Evidence for differing leukotriene receptors in gastric musosa. Europ. J. Pharmacol.125, 297–299 (1986).CrossRefGoogle Scholar
  5. [5]
    P. Salvati and B. J. R. Whittle,Investigation of the vascular actions of arachodonate lipoxygenase and cyclooxygenase products of the perfused stomach of rat and rabbit. Prostaglandin22, 141–156 (1981).CrossRefGoogle Scholar
  6. [6]
    K. D. Rainsford,An economical and highly sensitive assay for the gastrotoxicity of antiinflammatory drugs and anti-ulcer agents, in cholinomimetically-sensitized mice. Dig. Dis. Sci.30, A32 (1985).CrossRefGoogle Scholar
  7. [7]
    D. F. Magee, S. Naruse and A. Pap,Comparison of the actions of cholinomimetics and pentagastrin on gastric secretion in dogs. Br. J. Pharmacol.84, 347–355 (1985).PubMedGoogle Scholar
  8. [8]
    S. M. Coutts, A. Khandwala, R. Van Inwegen, U. Chakraborty, J. Musser, J. Bruens, N. Jariwala, V. Dally-Meade, R. Ingram, T. Puss, H. Jones, E. Neiss and I. Weinryb,Arylmethyl phenyl ethers. A new class of specific inhibitors of 5-lipoxygenase. InProstaglandins, leukotrienes, and lipoxins. (Ed. J. M. Bailey) pp. 627–637 Plenum Press, New York 1985.Google Scholar
  9. [9]
    Y. Guindon, Y. Girard, A. Maycock, A. W. Ford-Hutchinson, J. G. Atkinson, P. C. Belanger, A. Dallob, D. DeSousa, H. Dougherty, R. Egan, M. M. Goldenberg, E. Ham, R. Fortin, P. Hamel, R. Hamel, C. K. Lau, Y. Leblanc, C. S. McFarlane, H. Piechuta, M. Thérien, C. Yoakim and J. Rokach, L-651,392 a novel, potent and selective 5-lipoxygenase inhibitor. InAdvances in prostaglandins, thromboxane and leukotriene research. (Eds. B. Samuelsson et al.) pp. 554–557. Raven Press, New York 1987.Google Scholar
  10. [10]
    K. H. Leung,Selective inhibition of leukotriene C 4 synthesis in human neutrophils by ethacrynic acid. Biochem. Biophys. Res. Commun.137, 195–200 (1986).CrossRefPubMedGoogle Scholar
  11. [11]
    J. Augstein, J. B. Farmer, T. B. Lee, P. Sheard and M. L. Tattersall,Selective inhibitor of slow reacting substance of anaphylaxis. Nature New Biol.245, 215–217 (1973).PubMedGoogle Scholar
  12. [12]
    T. R. Jones, R. Young, E. Champion, L. Charette, D. Denis, A. W. Ford-Hutchinson, R. Frenette, J.-Y. Gauthier, Y. Guindon, M. Kakushima, P. Masson, A. Maycock, C. McFarlane, H. Piechuta, J. Rokach and R. Zamboni,L-649,923, sodium (βS *,γR *)-4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl-thio)-γ-hydroxy-β-methylbenzenebutanoate, a selective, orally active leukotriene acceptor antagonist. Can. J. Physiol. Pharmacol.64, 1068–1075 (1986).PubMedGoogle Scholar
  13. [13]
    J. H. Musser, D. M. Kubrak, J. Chang and A. J. Lewis,Synthesis of ((Naphthalenylmethoxy)- and ((quinolinylmethoxy)phenyl)amino)oxoalkanoic acid esters, A novel series of leukotriene D 4 antagonists and 5-lipoxygenase inhibitors. J. Med. Chem.29, 1429–1435 (1986).CrossRefPubMedGoogle Scholar
  14. [14]
    J. H. Fleisch, L. E. Rinkema, K. D. Haisch, D. Swanson-Bean, T. Goodson, P. P. K. Ho and W. S. Marshall,LY-171883, 1-(2-hydroxy-3-propyl-4-(4-(1H-tetrazol-5-yl) butoxyphenyl) ethanone, an orally active leukotriene D 4 antagonist. J. Pharmacol. Exp. Ther.233, 148–157 (1985).PubMedGoogle Scholar
  15. [15]
    G. Feuerstein,Autonomic pharmacology of leukotrienes. J. Auton. Pharmacol.5, 149–168 (1985).PubMedGoogle Scholar
  16. [16]
    J. Chang, personal communication.Google Scholar
  17. [17]
    K. D. Rainsford,Gastric ulcerogenicity of non-steroidal anti-inflammatory drugs in mice with mucosa sensitized by cholinomimetic treatment. J. Pharm. Pharmacol., in press (1987).Google Scholar

Copyright information

© Birkhäuser Verlag 1987

Authors and Affiliations

  • K. D. Rainsford
    • 1
  1. 1.Department of PharmacologyUniversity of CambridgeCambridgeEngland

Personalised recommendations