Skip to main content
Log in

Gastrointestinal damage induced by platelet-activating factor

Inhibition by the corticoid, dexamethasone

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Intravenous infusion of platelet-activating factor (PAF-acether) induces extensive vasocongestion and damage in the stomach and small intestine of the rat. The effect of pretreatment with the corticoid dexamethasone (2 mg/kg) on such gastrointestinal damage in the rat has now been investigated, using macroscopic observation and the release of acid phosphatase, as an enzyme marker of cell disruption. Administration of PAF-acether (100 ng/kg/min intravenously, for 10 min) induced focal, intense hyperemia and hemorrhage in all the regions of the gastrointestinal tract, with the exception of the distal colon. This damage was associated with an increase in the release of acid phosphatase into the lumen of the stomach, duodenum, jejunum, and ileum following incubation in vitro. Pretreatment with dexamethasone reduced the macroscopically apparent gastrointestinal damage following PAF-acether administration and abolished the intraluminal release of acid phosphatase. Dexamethasone also significantly suppressed the hemoconcentration, as determined by changes in platelet and erythrocyte count and hematocrit, 30 min after PAF-acether infusion. Thus, as in endotoxin shock, this glucocorticoid can reduce the gastrointestinal damage associated with PAF-acether administration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Whittle BJR, Kauffman GL, Moncada S: Vasoconstriction with thromboxane A2 induces ulceration of the gastric mucosa. Nature 292:472–474, 1981

    PubMed  Google Scholar 

  2. Whittle BJR, Oren-Wolman N, Guth PH: Gastric vasoconstrictor actions of leukotriene C4, PGF2α and thromboxane mimetic U-46619 on rat submucosal microcirculationin vivo. Am J Physiol 248:G580-G586, 1985

    PubMed  Google Scholar 

  3. Peskar BM, Lange K, Peskar BA: Ethanol stimulates formation of leukotriene C4 in rat gastric mucosa. Prostaglandins 31:283–293, 1986

    PubMed  Google Scholar 

  4. Benveniste J: PAF—a new mediator of anaphylaxis and immune complex deposition from rabbit and human basophils. Nature 249:581–582, 1974

    PubMed  Google Scholar 

  5. Vargaftig BB, Chignard M, Benveniste J, Lefort J, Wal F: Background and present studies of research on platelet-activating factor (PAF-acether). Ann NY Acad Sci 3710:119–137, 1981

    Google Scholar 

  6. Rosam A-C, Wallace JL, Whittle BJR: Potent ulcerogenic actions of platelet-activating factor on the stomach. Nature 319:54–56, 1986

    PubMed  Google Scholar 

  7. Wallace JL, Whittle BJR: Prevention of endotoxin-induced gastrointestinal damage by CV-3988, an antagonist of platelet-activating factor. Eur J Pharmacol 124:209–210, 1986

    PubMed  Google Scholar 

  8. Wallace JL, Whittle BJR: Picomole doses of platelet-activating factor predispose the gastric mucosa to damage by topical irritants. Prostaglandins 31:989–998, 1986

    PubMed  Google Scholar 

  9. Lagente V, Lidbury PS, Steel G, Vargaftig BB, Wallace JL, Whittle BJR: Role of PAF-acether as a mediator of endotoxin-induced gastrointestinal damage. Br J Pharmacol 90:114P, 1987

    Google Scholar 

  10. Mencia-Huerta JM, Benveniste J: Platelet-activating factor and macrophages. I. Evidence for the release from rat and mouse peritoneal macrophages and not from mastocytes. Eur J Immunol 9:409–415, 1979

    PubMed  Google Scholar 

  11. Humphrey DM, McManus LM, Satouchi K, Hanahan DJ, Pinckard RN: Vasoactive properties of acetyl glyceryl ether phosphorylcholine and analogues. Lab Invest 46:422–427, 1982

    PubMed  Google Scholar 

  12. Bessin P, Bonnet J, Thiboudeau D, Agier B, Beaudet Y, Gilet F: Pathophysiology of shock states caused by PAF-acether in dogs and rats.In Platelet-Activating Factor. INSERM Symposium No. 23. J Benveniste, B Arnoux (eds). Amsterdam, Elsevier, 1983, pp 343–356

    Google Scholar 

  13. Braquet P, Shen TY, Touqui L, Vargaftig BB: Perspectives in platelet activating factor research. Pharmacol Rev 39: 97–145

  14. Demopoulos CA, Pinckard RN, Hanahan DJ: Platelet-activating factor: Evidence for 1-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine as the active component (a new class of lipid chemical mediators). J Biol Chem 254:9355–9358

  15. Blackwell GJ, Carnuccio R, DiRosa M, Flower RJ, Parente L, Persico P: Macrocortin: A polypeptide causing the antiphospholipase effect of glucocorticoids. Nature 287:147–149, 1980

    PubMed  Google Scholar 

  16. Shumer W: Septic shock. JAMA 242:1906–1907, 1979

    PubMed  Google Scholar 

  17. Nicholson DP: Glucocorticoids in the treatment of shock and the adult respiratory distress syndrome. Clin Chest Med 3:121–132, 1982

    PubMed  Google Scholar 

  18. Wallace JL, Whittle BJR: Effects of inhibitors of arachidonic acid metabolism on PAF-acether-induced gastric mucosal necrosis and haemoconcentration. Br J Pharmacol 89:415–422, 1986

    PubMed  Google Scholar 

  19. 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, 1985

    PubMed  Google Scholar 

  20. Whittle BJR, Morishita T, Ohya Y, Leung FW, Guth PH: Microvascular actions of platelet-activating factor on the rat gastric mucosa and submucosa. Am J Physiol 251:G772-G778, 1986

    PubMed  Google Scholar 

  21. Wallace JL, Whittle BJR: Profile of gastrointestinal damage by platelet-activating factor. Prostaglandins 32:137–141, 1986

    PubMed  Google Scholar 

  22. Gonzalez-Crussi F, Hsueh W: Experimental model of ischaemic bowel necrosis. The role of platelet-activating factor and endotoxin. Am J Pathol 112:127–136, 1983

    PubMed  Google Scholar 

  23. Whittle BJR, Kauffman GL, Wallace JL: Gastric vascular and mucosal damaging actions of platelet activating factor in the canine stomach.In Adv Prostaglandin, Thromboxane, Leukotriene Res 17:285–292, 1987

    Google Scholar 

  24. Wallace JL, Whittle BJR, Boughton-Smith NK: Prostaglandin protection of rat colonic mucosa from damage induced by ethanol. Dig Dis Sci 30:866–876, 1985

    PubMed  Google Scholar 

  25. Hsueh W, Gonzalez-Crussi F, Arroyaue JL: Platelet-activating factor-induced ischaemic bowel necrosis. An investigation of secondary mediators in its pathogenesis. Am J Pathol 122:231–239, 1986

    PubMed  Google Scholar 

  26. Hsueh W, Gonzalez-Crussi F, Arroyaue JL: Release of leukotriene C4 by isolated, perfused rat small intestine in response to platelet-activating factor. J Clin Invest 78:108–114, 1986

    PubMed  Google Scholar 

  27. Salmon JA, Simmons PM, Moncada S: The effects of BW755C and other anti-inflammatory drugs on eicosanoid concentrations and leukocyte accumulation in experimentally induced acute inflammation. J Pharm Pharmacol 35:808–813, 1983

    PubMed  Google Scholar 

  28. Wallace JL, Whittle BJR: Role of prostaglandins in the protective actions of BW755C on the gastric mucosa. Eur J Pharmacol 115:45–52, 1985

    PubMed  Google Scholar 

  29. Dahlen SE, Bjork J, Hedqvist P, Arfors K-E, Hammarstrom S, Lindgren JA, Samuelsson B: Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules:In vivo effects with relevance to the acute inflammatory response. Proc Natl Acad Sci USA 78:3887–3891, 1981

    PubMed  Google Scholar 

  30. Bourgain RH, Maes L, Braquet P, Anduis R, Touqui L, Braquet M: The effect of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF-acether) on the arterial wall. Prostaglandins 30:185–187, 1985

    PubMed  Google Scholar 

  31. Parente L, Flower RJ: Hydrocortisone and ‘'macrocortin’' inhibit zymosan-induced release of lyso-PAF from rat peritoneal leukocytes. Life Sci 36:1225–1231, 1985

    PubMed  Google Scholar 

  32. Ferguson WW, Starling JR, Wangensteen SL: Role of lysosomal enzyme release in the pathogenesis of stress-induced gastric ulceration. Surg Forum 23:380–382, 1972

    PubMed  Google Scholar 

  33. Pfeiffer CJ, Cho CI, Cheema A, Saltman D: Reserpine-induced gastric ulcers: Protection by lysosomal stabilization due to zinc. Eur J Pharmacol 60:347–353, 1980

    Google Scholar 

  34. Polson H, Mowat C, Himal HS: Increased mucosal lysosomal enzyme activity in sepsis-associated gastric lesions. Am J Gastroenterol 77:457–460, 1982

    PubMed  Google Scholar 

  35. Mowat CE, Himal HS: The effect of methylprednisolone on bile-treated gastric mucosal lysosomes. Am J Gastroenterol 78:554–556, 1983

    PubMed  Google Scholar 

  36. Doebber JW, Wu WS, Shen TY: Platelet activating factor intravenous infusion in rats stimulates vascular lysosomal hydrolase secretion independent of blood neutrophils. Biochem Biophys Res Commun 125:980–987, 1984

    PubMed  Google Scholar 

  37. Doebber TW, Wu MS, Robbins JC, Choy M, Chang MN, Shen TY: Platelet activating factor (PAF) involvement in endotoxin-induced hypotension in rats. Studies with PAF-receptor antagonist kadsurenone. Biochem Biophys Res Commun 127:799–808

  38. Terashita Z, Imura Y, Nishikawa K, Sumida S: Is platelet activating factor (PAF) a mediator of endotoxin shock? Eur J Pharmacol 109:257–261

Download references

Author information

Authors and Affiliations

Authors

Additional information

Dr. J.L. Wallace is the recipient of a scholarship from the Medical Research Council of Canada.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wallace, J.L., Whittle, B.J.R. Gastrointestinal damage induced by platelet-activating factor. Digest Dis Sci 33, 225–232 (1988). https://doi.org/10.1007/BF01535737

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01535737

Key words

Navigation