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1991 | 42 | 2 |

Tytuł artykułu

Leukotrienes in mucosal damage and protection

Autorzy

Treść / Zawartość

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
Exposure of the rat gastric mucosa to ethanol stimulates the generation of leukotriene (LTC₄) and 15-hydroxyeicosatetraenoic acid, hut not of thromboxanes and prostaglandins. Lipoxygenase activation is not found with other topical irritants or nonsteroidal anti-inflammatory drugs. A number of gastroprotective drugs dose-dependently inhibit the stimulatory action of ethanol on mucosal LTC₄ formation closely parallel to their protective activity suggesting that ethanol-induced damage and activation of lipoxygenases may involve common targets which are simultaneously counteracted by certain types of protective agents. Selective inhibition of 5-lip- oxygenase, however, does not confer protection against gastric mucosal damage caused by topical irritants or non-steroidal anti-inflammatory drugs. Thus, although leukotrienes may mediate certain reactions elicited by gastric ulcerogens such as submucosal venular constriction and mucosal micro vascular engorgement, they do not appear to be major mediators of ulcerogen-induced tissue necrosis. The contribution of other products of the various pathways of arachidonic acid metabolism to gastric mucosal injury and the mechanism underlying the close interrelationship between protection and inhibiton of LTC₄ formation observed with certain compounds remains to be investigated.

Wydawca

-

Rocznik

Tom

42

Numer

2

Opis fizyczny

p.135-145,fig.,ref.

Twórcy

autor
  • Departament of Experimental Clinical Medicine, Ruhr-University of Bochum, Universitalsstresse 150, D-4630 Bochum, Germany

Bibliografia

  • 1. Piper PJ. Formation and actions of leukotrienes. Physiol Rev 1984; 64: 744-61.
  • 2. Dembinska-Kieć A, Peskar BA, Müller MK, Peskar BM. The effects of platelet-activating factor on flow rate and eicosanoid release in the isolated perfused rat gastric vascular bed. Prostaglandins 1989; 37: 69-91.
  • 3. Peskar BM. Role of cysteinyl leukotrienes in gastric mucosal damage in rats. Adv Prostaglandin Thromboxane Leukotriene Res 1989; 19: 552-555.
  • 4. Whittle ВJR, Oren-Wolman N, Guth PH. Gastric vasoconstrictor actions of leuko- triene C₄, PGE₂, and thromboxane mimetic U-46619 on rat submucosal microcirculation in vivo. Am J Physiol 1985; 248: G580-586.
  • 5. Dahlén SE, Björk J, Hedquist P, et al. Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: In vivo effects with relevance to the acute inflammatory response. Proc Natl Acad Sci 1981; 78: 3887-3891.
  • 6. Pihan G, Rogers C, Szabo S. Vascular injury in acute gastric mucosal damage. Mediatory role of leukotrienes. Dig Dis Sci 1988; 33: 625-632.
  • 7. Konturek SJ, Brzozowski T, Drozdowicz D, Beck G. Role of leukotrienes in acute gastric lesions induced by ethanol, taurocholate, aspirin, platelet activating factor and stress in rats. Dig Dis Sci 1988; 33: 806-813.
  • 8. Guth PH, Paulsen G, Nagata H. Histologic and microcirculatory changes in alcohol-induced gastric lesions in the rat: Effect of prostaglandin cytoprotection. Gastroenterology 1984; 87: 1083-1090.
  • 9. Szabo S, Trier JS, Brown A, Schnoor J. Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat. Gastroenterology 1985; 88: 228-236.
  • 10. Oates PJ, Hakkinen JP. Studies on the mechanism of ethanol-induced gastric damage in rats. Gastroenterology 1988; 94: 10-21.
  • 11. Peskar BM, Lange K, Hoppe U, Peskar BA. Ethanol stimulates formation of leuko- triene C₄ in rat gastric mucosa. Prostaglandins 1986; 31: 283-293.
  • 12. Summers JB, Gunn BP, Martin JG, et al. Orally active hydroxyamic acid inhibitors of leukotriene biosynthesis. J Med Chem 1988; 31: 3-5.
  • 13. Peskar BM. Lipoxygenase products in gastric damage and protection. Adv Prostaglandin Thromboxane Leukotriene Res 1990; 21: 753-760.
  • 14. Wallace JL, Whittle В JR. Role of prostanoids in the protective actions of BW755C on the gastric mucosa. Eur J Pharmacol 1985; 115: 45-52.
  • 15. Peskar BM. Role of leukotriene C₄ in mucosal damage caused by necrotizing agents and indomethacin in the rat stomach. Gastroenterology 1991; 100: 619-626
  • 16. Trautmann M, Peskar BM, Peskar BA. Gastroprotection by non-steroidal antiinflammatory drugs in rats: lack of correlation to effects on the gastric mucosal prostaglandin and leukotriene system. Gastroenterology 1989; 96: A514.
  • 17. Peskar BM, Hoppe U, Lange K, Peskar BA. Effects of non-steroidal anti-inflammatory drugs on rat gastric mucosal leukotriene C₄ and prostanoid release: relation to ethanol-induced injury. Br J Pharmacol 1988; 93: 937-943.
  • 18. Kröner EE, Peskar BA, Fischer H, Ferber E. Control of arachidonic acid accumulation in bone marrow-derived macrophages by асуltransferases. J. Biol Chem 1981; 256: 3690-3697
  • 19. Lange K, Peskar BA, Peskar BM. Stimulation of rat gastric mucosal leukotriene C₄ formation by ethanol and effect of gastric protective drugs. Adv Prostaglandin Thromboxane Leukotriene Res 1987; 17: 299-302.
  • 20. Trautmann M, Peskar BM. Gastroprotection in rats by the antacids hydrotalcit and maalox does not involve the endogenous prostaglandin and leukotriene system. Gastroenterology 1990; 98: A139.
  • 21. Holzer P, Pabst MA, Lippe ITh, et al. Afferent nerve-mediated protection against deep mucosal damage in the rat stomach. Gastroenterology, 1990; 98: 838-48.
  • 22. Yonei Y, Wayland H, Guth PH. Role of arachidonic acid metabolites in ethanol vasoaction in rat gastric submucosa. Am J Physiol 1988; 255: G731-737.
  • 23. Yonei Y, Guth PH. Lipoxygenase metabolites in the rat gastric microvascular response to intragastric ethanol. Gastroenterology 1989; 97: 304-312.
  • 24. Beck IT, Boyd AJ, Dinda PK. Evidence for the involvement of 5-lipoxygenase products in ethanol-induced intestinal plasma protein loss. Am J Physiol 1988; 254: G483-488.
  • 25. Wallace JL, Beck PL, Morris GP. Is there a role for leukotrienes as mediators of ethanol-induced gastric mucosal damage? Am J Physiol 1988; 254: G117-23.
  • 26. Boughton-Smith NK, Whittle BJR. Failure of the inhibition of the rat gastric mucosal 5-lipoxygenase by novel acetohydroxamic acids to prevent ethanol-induced damage. Br J Pharmacol 1988; 95: 155-162
  • 27. Konturek SJ, Brzozowski T, Drozdowicz D, Garlicki J, Beck G. Role of leukotrienes and platelet activating factor in acute gastric mucosal lesions in rats. Eur J Pharmacol 1989; 164: 285-292.
  • 28. Peskar BM. Cysteinyl-leukotriene receptor antagonists protect against ethanol- and indomethacin-induced gastric mucosal damage in rats. Gastroenterology 1988; 94: A351.
  • 29. Nielsen ST, Beninati L, Chang J. REV 5901 and LY 171, 883 protect rat gastric mucosa against ethanol-induced damage. Agents Actions 1987; 21: 320-322.
  • 30. Foster SJ, Aked DM, McCormick ME, Potts HC. Cytoprotective properties of ICI 207968, a selective 5-lipoxygenase inhibitor, on the rat gastrointestinal mucosa. Br J Pharmacol 1989; 96: 38P
  • 31. Aehringhaus U, Dembinska-Kiéc A, Peskar BA. Effects of exogenous prostaglandins on the release of leukotriene C₄-like immunoreactivity and on coronary flow inindomethacin-treated anaphylactic guinea-pig hearts. Naunyn-Schmiedeberg’s Arch Pharmacol 1984; 326: 368-374.
  • 32. Ham EA, Soderman DD, Zanetti ME, Dougherty HW, McCauley E, Kuehl FA. Inhibition by prostaglandins of leukotriene B₄ release from activated neutrophils. Proc Natl Acad Sci 1983; 80: 4349-4353.
  • 33. Rainsford KD. The effects of 5-lipoxygenase inhibitors and leukotrienes antagonists on the development of gastric lesions induced by nonsteroidal antiinflammatory drugs in mice. Agents Actions 1987; 21: 316-319.

Typ dokumentu

Bibliografia

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