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Some of the factors that may mediate or modify the gastrointestinal mucosal damage induced by non-steroidal anti-inflammatory drugs

  • Papers Presented at the Joint Meeting of the European Inflammation Society and Hungarian Biochemical Society Balatonaliga, Hungary, 19–21 May, 1993
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Abstract

Numerous factors are involved in the gastro-intestinal mucosal damage induced by non-steroidal anti-inflammatory drugs. The physico-chemical — acidic — property of the drugs is responsible partly for the rapid absorption, mucosal accumulation and barrier breaking effect, partly for the topical irritant action. The drugs decrease the defensive mechanisms of the stomach at different level, destroy the mucosal barrier, decrease the surface hydrophobicity, the mucosal blood flow, and inhibit the prostaglandin synthesis. Exogenous sulfhydryls and interleukin-1 inhibit the NSAID-induced mucosal damage, whether they are also involved in the ulcerogenic action has not been clearly determined. On the other hand, injurious factors are also stimulated; enhanced gastric acid secretion, increased pepsin activity, enhanced formation of free radicals and leukotrienes, as well as activation of leukocyte can also contribute to the mucosal lesions induced by NSAIDs. Prior Campylobacter pylori infection may make the mucosa more susceptible to NSAID-associated injury.

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References

  1. K. Brune, P. Graf and K. D. Rainsford,A pharmacokinetic approach to the understanding of therapeutic effects and side-effects of salicylates. Agents and Actions Suppl. 1, 9–26 (1977).

    Google Scholar 

  2. H. W. Davenport,Salicylate damage to the gastric mucosal barrier. New. Engl. J. Med.276, 1307–1312 (1967).

    PubMed  Google Scholar 

  3. B. K. Martin,Accumulation of drug anions in gastric mucosal cells. Nature198, 896–897 (1963).

    Google Scholar 

  4. H. W. Davenport,Damage to the gastric mucosa: Effects of salicylates and stimulation. Gastroenterology49, 189–196 (1965).

    PubMed  Google Scholar 

  5. K. McCormack and K. Brune,Classical absorption theory and the development of gastric mucosal damage associated with the non-steroidal anti-inflammatory drugs. Arch. Toxicol.60, 261–269 (1987).

    Article  PubMed  Google Scholar 

  6. R. I. Takesue, J. W. Perrine and J. H. Trapold,The anti-inflammatory profile of proquazone. Arch. int. Pharmacodyn. Ther.221, 122–131 (1976).

    PubMed  Google Scholar 

  7. M. W. Whitehouse and K. D. Rainsford,Esterification of acidic anti-inflammatory drugs suppress their gastrotoxicity without adversely affecting their anti-inflammatory activity in rats. J. Pharm. Pharmacol.32, 795–796 (1980).

    PubMed  Google Scholar 

  8. J. L. A. Roth, A. Valdez-Depena, P. Pieses et al.,Topical action of salicylates in gastrointestinal erosion and heamorrhage. Gastroenterology44, 389–391 (1963).

    Google Scholar 

  9. K. Brune, B. Nurnberg, I. Szelenyi and H. Vergin,The enterohepatic circulation of some anti-inflammatory drugs may cause intestinal ulcers. InSide-Effects of Anti-Inflammatory Drugs. (Eds. K. D. Rainsford and G. P. Velo) pp. 29–39. MTP Press, Lancester 1986.

    Google Scholar 

  10. K. D. Rainsford,Mechanism of gastric contrasted with intestinal damage by non-steroidal anti-inflammatory drugs. InSide-Effects of Anti-Inflammatory Drugs (Eds. K. D. Rainsford and G. P. Velo) pp. 3–28, MTP Press, Lancester 1986.

    Google Scholar 

  11. M. W. Whithouse and K. D. Rainsford, Comparison of the ulcerogen action of different salicylates. (Ed. C. J. Pfeiffer) pp. 127–141, CRC Press Boca Raton, Florida 1982.

    Google Scholar 

  12. K. D. Rainsford and M. W. Whithouse,Biochemical gastro-protection from acute ulceration induced by aspirin and related drugs. Biochem. Pharmacol.29, 1281–1289 (1980).

    Article  PubMed  Google Scholar 

  13. R. Menguy and Y. F. Masters,Effect of aspirin on gastric mucous secretion. Surg. Gynecol. Obstet.120, 92–98 (1965).

    PubMed  Google Scholar 

  14. R. Menguy and L. Desbailetts,Influence of phenylbutazone on gastric secretion of mucus. Proc. Soc. Exp. Biol. Med.125, 1108–1111 (1967).

    PubMed  Google Scholar 

  15. W. D. W. Rees, Mucus bicarbonate barrier — shield or sieve? Gut28, 1553–1556 (1987).

    PubMed  Google Scholar 

  16. J. L. Wallace and G. W. McKnight,The mucoid cap over superficial gastric damage in the rat. Gastroenterology99, 295–304 (1990).

    PubMed  Google Scholar 

  17. I. N. Ross and L. A. Turnberg,Studies on the mucus bicarbonate barrier on rat fundic mucosa: The effect of luminal pH and prostaglandin analogue. Gut24, 1030–1033 (1983).

    PubMed  Google Scholar 

  18. B. D. Buttler, L. M. Lichtenberger and B. A. Hills,Distribution of the surfactants in the canine gastrointestinal tract and their ability to lubricate. Am. J. Physiol.244, G645–651 (1983).

    PubMed  Google Scholar 

  19. A. Hills, B. D. Buttler and L. M. Lichtenberger,Gastric mucosal barrier: Hydrophobic lining to the lumen of the stomach. Am. J. Physiol.244, 567–568 (1983).

    Google Scholar 

  20. L. M. Lichtenberger, J. E. Richards and B. A. Hills,Effect of 16,-16-dimethyl prostaglandin E 2 on the surface hydrophobicity of aspirin-treated canine gastric mucosa. Gastroenterology88, 308–314 (1985).

    PubMed  Google Scholar 

  21. P. J. Goddard, Y. C. J. Kao and L. M. Lichtenberger,Aspirin (ASA) damages gastric surface mucus cells (SMC) despite maintenance of surface hydrophobicity by 16,-16-dimethyl-prostaglandin E 2 (PG) (Abstract). Gastroenterology92, 1800 (1987).

    Google Scholar 

  22. W. A. Mersereau and E. J. Hinchey,Effect of gastric acidity on gastric ulceration induced by heamorrhage in the rat, utilizing a gastric chamber technique Gastroenterology64, 1130–1135 (1973).

    PubMed  Google Scholar 

  23. W. P. Richtie and E. W. Shearburn,Influence of isoproterenol and cholestyramine on acute mucosal ulcerogenesis. Gastroenterology73, 62–65 (1977).

    PubMed  Google Scholar 

  24. P. H. Guth,Gastric mucosal blood flow and resistance to injury. InAdvances in Ulcer Diseases (Eds. K. H. Holzermuller and J. R. Malagelada) pp. 101–109, Excrepta Medica, Amsterdam 1980.

    Google Scholar 

  25. M. A. Perry, S. Wadahava, D. A. Parks, N. Pickard and D. N. Granger,Role of oxygen free radicals in ischemia induced lesions in the cat stomach. Gastroenterology90, 362–367 (1986).

    PubMed  Google Scholar 

  26. J. F. Gerkens, D. G. Shand, C. Flexner, A. S. Nies, J. A. Oates and J. L. Data,Effect of indomethacin and aspirin on gastric blood flow and acid secretion. J. Pharmacol. Exp. Ther.203, 246–652 (1977).

    Google Scholar 

  27. L. R. Johnson and B. F. Overholt,Release of histamine into gastric venous blood following injury by acetic or salicylic acid. Gastroenterology52, 505–509 (1967).

    PubMed  Google Scholar 

  28. H. Hirose, K. Takeuch and S. Okabe,Effect of indomethacin on gastric mucosal blood flow around acetic acid-induced gastric ulcers in rats. Gastroenterology100, 1259–1265 (1991).

    PubMed  Google Scholar 

  29. A. Robert,Cytoprotection by prostaglandins. Gastroenterology77, 761–767 (1979).

    PubMed  Google Scholar 

  30. G. Pihan, D. Majzoubi, C. Haudenschield, S. J. Trier and S. Szabo,Early microcirculatory stasis in acute gastric mucosal injury in the rat and prevention by 16,-16-dimethyl prostaglandin E 2 or sodium thiosulfate. Gastroenterology,91, 1415–1426 (1986).

    PubMed  Google Scholar 

  31. J. M. Henagan, K. L. Schmidt and T. A. Miller,Prostaglandin prevents aspirin injury in the canine stomach under in vivo but not in vitro conditions. Gastroenterology97, 649–659 (1989).

    PubMed  Google Scholar 

  32. H. Asako, P. Kubes, J. Wallace, T. Gaginella, R. E. Wolf and D. N. Granger,Indomethacin-induced leukocyte adhesion in mesenteric venules: Role of lipoxygenase products. Am. J. Physiol.262, G903–908 (1992).

    PubMed  Google Scholar 

  33. H. Asako, P. Kubes, J. Wallace, R. E. Wolf and D. N. Granger,Modulation of leukcyta adherence in rat mesenteric venules by aspirin and salicylates. Gastroenterology103, 146–152 (1992).

    PubMed  Google Scholar 

  34. M. I. Grossman, K. K. Matsumoto and R. J. Lichter,Fecal blood loss produced by oral and intravenous administration of various salicylates. Gastroenterology40, 383–388 (1961).

    PubMed  Google Scholar 

  35. B. J. R. Whittle, G. A. Higgs, K. E. Eakins, S. Moncada and J. R. Vane,Selective inhibition of prostaglandin production in inflammatory exudate and gastric mucosa. Nature284, 271–273 (1980).

    Article  Google Scholar 

  36. K. D. Rainsford and C. Willis,Relationship of gastric mucosal damage induced in pigs by anti-inflammatory drugs to their effects on prostaglandin production. Dig. Dis. Sci.27, 624–635 (1982).

    Article  PubMed  Google Scholar 

  37. M. Ligumsky, E. M. Golanska and D. L. Kauffman,Aspirin can inhibit gastric mucosal cyclo-oxygenase without causing lesions in rat Gastroenterology84, 756–761 (1983).

    PubMed  Google Scholar 

  38. T. Shea-Donohue, L. Steel, E. Montcalm-Mazzilli and A. Dubois,Aspirin-induced changes in gastric function: role of endogenous prostaglandins and mucosal damage. Gastroenterology98, 284–292 (1990).

    PubMed  Google Scholar 

  39. S. Szabo, J. S. Trier and P. W. Frankel,Sulfhydryl compounds may mediate gastric cytoprotection. Science214, 200–202 (1981).

    PubMed  Google Scholar 

  40. O. Strubelt and R. Hoppenkamps,Relations between gastric glutathione and the ulcerogenic action of non-steroidal anti-inflammatory drugs. Arch. int Pharmacodyn. Ther.262, 268 (1983).

    PubMed  Google Scholar 

  41. K. Gyires,Influence of different anti-inflammatory substances on ethanol- and indomethacin-induced gastrointestinal mucosal damage. InInflammation and Drug Therapy Series, Vol. 5.Side-Effects of Anti-Inflammatory Drugs, Vol. 3 (Eds. K. D. Rainsford and G. P. Velo) pp. 350–358, Kluwer, Dordrecht 1992.

    Google Scholar 

  42. N. S. Kosower and E. M. Kosower,The glutathion status of cells. Int. Rev. Cytol.54, 109–160 (1978).

    PubMed  Google Scholar 

  43. S. Szabo, J. S. Trier, A. Brown and J. Schonoar,Early vascular injury and increased permeability in gastric mucosal injury caused by ethanol in the rat. Gastroenterology88, 228–236 (1985).

    PubMed  Google Scholar 

  44. A. Allen,Structure of gastrointestinal mucus glycoproteins and the viscous and gel-forming property of mucus. Br. Med. Bull.34, 28–33 (1978).

    PubMed  Google Scholar 

  45. K. Gyires,Morphine inhibits the ethanol-induced gastric damage in rats. Arch. Int. Pharmacodyn. Ther.35/1–2, 170–181 (1990).

    Google Scholar 

  46. K. Gyires, I. Hermecz and J. Knoll,Recent data on inhibition of mucosal damage by pyrido-pyrimidines. InUlcer Disease: New Aspects of Pathogenesis and Pharmacology (Eds., S. Szabo and C. J. Pfeiffer) pp. 381–392, CRC Press, Boca Raton, Florida 1989.

    Google Scholar 

  47. I. Szelenyi and K. Brune, Possible role of sulfhydryls in mucosal protection induced by aluminium hydroxide. Dig. Dis. Sci.31, 1207–1210 (1986).

    Article  PubMed  Google Scholar 

  48. S. Konturek, T. Brzozowski, I. Piastucki, T. Radecki and S. Szabo,Gastric cytoprotection by agents altering gastric mucosal sulfhydryl compounds: Role of endogenous prostaglandins. InAdvances in Prostaglandin and Thromboxane Research. Vol. 12. (Eds. B. Samuelsson, R. Paoletti and P. Ramwell) pp. 411–416, Raven Press, New York 1983.

    Google Scholar 

  49. D. Dupuy, A. Raza and S. Szabo,The role of endogenous nonprotein and protein sulfhydryls in gastric mucosal injury and protection. InUlcer Disease: New Aspects of Pathogenesis and Pharmacology (Eds. S. Szabo, C. J. Pfeiffer) pp. 421–434, CRC Press, Boca Raton, Florida 1989.

    Google Scholar 

  50. J. L. Wallace, C. M. Keenan, K. G. Mugridge and L. Parenete,Reduction of the severity of experimental gastric and duodenal ulceration by interleukin-1β. Eur. J. Pharmacol.86, 279–284 (1990).

    Article  Google Scholar 

  51. A. Robert, A. S. Olaffson, C. Lancaster and W. R. Zhang,Interleukin-1 is cytoprotective, stimulates PGE 2 synthesis by the stomach, and retards gastric emptying. Life Sci.48, 123–134 (1991).

    Article  PubMed  Google Scholar 

  52. A. Uehara, T. Okumura, C. Sekiya, K. Okumura, Y. Takasugi and M. Namika,Interleukin-1 inhibits the secretion of gastric acid in rats: Possible involvement of prostaglandins. Biochem. Biophys. Res. Commun.162, 1578–1584 (1989).

    Article  PubMed  Google Scholar 

  53. K. G. Mugridge, M. Peretti, J. L. Wallace and L. Parente,Possible factors involved in the protective effect of interleukin-1 in aspirin and indomethacin-induced gastric damage. InInflammation and Drug Therapy Series. Vol. V.Side-Effects of Anti-Inflammatory Drugs (Eds. K. D. Rainsford and G. P. Velo) pp. 135–144 Kluwer, Dordrecht 1992.

    Google Scholar 

  54. R. J. Smith, S. C. Speciale and B. J. Bowman,Properties of interleukin-1 as a complete secretagogue for human neutrophils. Biochem. Biophys. Res. Commun.130, 1233–1240 (1985).

    Article  PubMed  Google Scholar 

  55. K. D. Rainsford,Prevention of indomethacin-induced gastro-intestinal ulceration in rats by glucose-citrate formulations: Role of ATP in mucosal defense. Br. J. Rheumatol.26 (Abst Suppl. 2), 81 (1987).

    PubMed  Google Scholar 

  56. H. W. Davenport,Fluid produced by gastric mucosa during damage by acetic acid and salicylic acid. Gastroenterology50, 487–499 (1966).

    PubMed  Google Scholar 

  57. T. H. Chavasta and A. R. Cook,The effect of several ulcerogenic drugs on the canine mucosal barrier. J. Lab. Clin. Med.79, 302–315 (1972).

    PubMed  Google Scholar 

  58. E. D. Jacobson,Circulatory mechanisms of gastric mucosal damage and protection. Gastroenterology102, 1788–1800 (1992).

    PubMed  Google Scholar 

  59. K. J. Ivey,Drugs, gastritis and peptic ulcers. Clin. Gastroenterol.3 (Suppl. 2), 29–34 (1981).

    Google Scholar 

  60. K. J. Ivey, W. N. Baskin, W. J. Krause and B. Terry,The effect of aspirin and acid on human gastric jejunal mucosa: An ultrastructural study. Gastroenterology76, 50–56 (1979).

    PubMed  Google Scholar 

  61. R. A. Levine, J. Nandi and R. L. King,Nonsalicylate nonsteroidal anti-inflammatory drugs augment prestimulated acid secretion in rabbit parietal cells. Gastroenterology101, 756–765 (1991).

    PubMed  Google Scholar 

  62. U. K. Murthy and R. A. Levine,Aspirin induces morphological transformation to the secretory state in isolated rabbit parietal cells. Gastroenterology101, 404–409 (1991).

    PubMed  Google Scholar 

  63. P. H. Rowe, M. J. Starlinger, E. Kasdon, G. Marrone and W. Silen,Effect of stimulated systemic administration of aspirin, salicylate and indomethacin on amphibian gastric mucosa. Gastroenterology90, 559–569 (1986).

    PubMed  Google Scholar 

  64. G. Kaufman,Aspirin-induced gastric mucosal injury: lessons learned from animal models. Gastroenterology96, 606–614 (1989).

    PubMed  Google Scholar 

  65. K. D. Rainsford,The effect of 5-lipoxygenase inhibition and leukotriene antagonists on the development of gastric lesions induced by non-steroidal anti-inflammatory drugs in mice. Agents and Actions21, 316–319 (1987).

    Article  PubMed  Google Scholar 

  66. S. J. Konturek, T. Brzozowski, D. Drodowicz and G. Beck,Role of leukotrienes in acute gastric lesions induced by ethanol, taurocholate, aspirin, platelet activating factor and stress in rats. Dig. Dis. Sci.33/7, 806–813 (1988).

    Article  Google Scholar 

  67. B. J. R. Whittle,Arachidonic acid metabolities and the gastro-intestinal toxicity of anti-inflammatory agents. Prostaglandins21, 113–118 (1981).

    Article  Google Scholar 

  68. B. M. Peskar,Role of leukotriene C 4 in mucosal damage caused by necrotizing agents and indomethacin in the rat stomach. Gastroenterology100, 619–626 (1991).

    PubMed  Google Scholar 

  69. B. M. Peskar, U. Hoppe, K. Lange and B. A. Peskar,Effects of non-steroidal anti-inflammatory drugs on rat gastric mucosal leukotriene C 4and prostanoid release — relation to ethanol-induced injury. Br. J. Pharmacol.93, 937–943 (1988).

    PubMed  Google Scholar 

  70. K. D. Rainsford,Mechanism of gastrointestinal toxicity of non-steroidal anti-inflammatory drugs. Scand. J. Gastroenterol.24 (Suppl. 163), 9–16 (1989).

    PubMed  Google Scholar 

  71. B. J. R. Whittle, N. Oren-Wolman and P. H. Guth,Gastric vasoconstrictor action of leukotriene C 4 PGF2α,and thromboxane mimetic U-46619 on rat submucosal microcirculation in vivo. Am. J. Physiol.248, G850–856 (1985).

    Google Scholar 

  72. G. Pihan, C. Rogers and S. Szabo,Vascular injury in acute gastric vascular damage. Mediatory role of leukotrienes. Dig. Dis. Sci.33, 625–632 (1988).

    Article  PubMed  Google Scholar 

  73. B. A. Freeman and J. D. Crapo,Biology of disease. Free radicals and tissue injury. Lab. Invest.47, 412–426 (1982).

    PubMed  Google Scholar 

  74. M. Suematsu, M. Suzuki, H. Nagato, S. Miura, S. Houzawa, T. Morishita and M. Tsuchiya,Role of neutrophil-mediated oxidative stress in acute gastric mucosal injury, induced by microvascular derrangement. InFree Radicals in Digestive Diseases (Ed. M. Tsuchiya) pp. 67–72, Elsevier Science, Amsterdam 1988.

    Google Scholar 

  75. R. J. Gryglewski, R. M. J. Palmer and S. Moncada,Superoxide anion is involved in the breakdown of, endothelium derived vascular relaxing factor. Nature320, 454–456 (1986).

    PubMed  Google Scholar 

  76. P. Del Soldato, D. Foschi, G. Benoni, C. Scarpignato,Oxygen free radicals interact with indomethacin to, cause gastrointestinal injury. Agents and Actions17, 484–488 (1985).

    Article  Google Scholar 

  77. J. Krupinska, H. Sobanski, J. Piotrowicz, B. Cebo and J. Mazur,Antioxidant agents reducing the toxicity of indomethacin. Acta Biol. Med. Ger.39, 717–721 (1980).

    PubMed  Google Scholar 

  78. G. Pihan, C. Regillo and S. Szabo,Free radicals and lipid peroxidation in ethanol- and aspirin-induced gastric mucosal injury. Dig. Dis. Sci.32/12, 1395–1401 (1987).

    Article  Google Scholar 

  79. T. Kitahora and P. H. Guth,Effect of aspirin plus hydrochloric acid on the gastric mucosal microcirculation. Gastroenterology93, 810–817 (1987).

    PubMed  Google Scholar 

  80. J. L. Wallace, C. M. Keenan and D. N. Granger,Gastric ulceration induced by non-steroidal anti-inflammatory drugs is a neutrophil dependent process. Am. J. Physiol.259, G462–467 (1990).

    PubMed  Google Scholar 

  81. E. A. Ham, D. D. Soderman, M. E. Zanetti, H. W. Dougherty, E. McCauley and F. A. Kuehl,Inhibition of prostaglandins of leukotriene B 4 release from activated neutrophils. Proc. Natl. Acad. Sci. USA80, 4349–4353 (1983).

    PubMed  Google Scholar 

  82. D. A. Parks, D. N. Granger, G. B. Bulkley and A. K. Shan,Soyabean trypsin inhibitor attenuates ischemic injury to the feline small intestine. Gastroenterology89, 6–12, (1985).

    PubMed  Google Scholar 

  83. D. Y. Graham, P. D. Klein, A. R. Opekun and T. W. Boutton,Effect of age on the frequency of active Campylobacter infection diagnosed by the (13C) urea breath test in normal subjects and patients with peptic ulcer disease. J. Infect. Dis.157, 777–780 (1988).

    PubMed  Google Scholar 

  84. B. L. Slomiany, J. Biliski, J. Sarosiek, L. Murty, B. Dworkin, K. Van Horn, J. Zielenski and A. Slomiany,Campylobacter pylorides degrades mucin and undermines gastric mucosal integrity. Biochem. Biophys. Res. Commun.144, 307–314 (1987).

    Article  PubMed  Google Scholar 

  85. D. Y. Graham, M. D. Lidsky, A. M. Cox, D. J. Evans, D. G. Evans, L. Alpert, P. D. Klein, S. L. Sessoms, P. A. Michaletz and Z. A. Saeed,Long-term nonsteroidal anti-inflammatory drug use and Heliobacter pylori infection. Gastroenterology100, 1653–1657 (1991).

    PubMed  Google Scholar 

  86. I. Bjarson and A. Macpherson,The changing gastrointestinal side-effect profile of non-steroidal anti-inflammatory drugs. Scand. J. Gastroenterol.24 (Suppl. 163), 56–64 (1989).

    Google Scholar 

  87. M. J. S. Langman, L. Morgen and A. Worral,Use of anti-inflammatory drugs by patients admitted with small or large bowel perforation and heamorrhage. Br. Med. J.290, 347–349 (1985).

    Google Scholar 

  88. P. Del Soldato, A. Meli and G. Volterra,Influence of fasting and cimetidine on the relationship between ulcerogenic and anti-inflammatory property of indomethacin. Br. J. Pharmacol.67, 33–37 (1979).

    PubMed  Google Scholar 

  89. P. Del Soldato and A. Meli,Studies of fat free diet (FFD) protection against indomethacin-induced intestinal lesions. Proc. Soc. Exp. Biol. Med.158, 19–22 (1978).

    PubMed  Google Scholar 

  90. A. Robert and T. Asano,Resistence of germ-free rats to indomethacin-induced intestinal lesions. Prostaglandins14, 333–341 (1977).

    Article  PubMed  Google Scholar 

  91. T. H. Kent, R. M. Cardelli and F. W. Stamler,Small intestinal ulcers and intestinal flora in rats given indomethacin. Am. J. Pathol.54, 237–245 (1969).

    PubMed  Google Scholar 

  92. A. Robert,An intestinal disease produced by prostaglandin deficiency. Gastroenterology69, 1045–1047 (1975).

    PubMed  Google Scholar 

  93. B. J. R. Whittle,Temporal relationship between cyclooxygenase inhibition, as measured by prostacyclin biosynthesis, and gastrointestinal damage by indomethacin in the rat. Gastroenterology80, 94–98 (1981).

    PubMed  Google Scholar 

  94. S. Miura, M. Suematsu and S. Tanaka et al.,Microcirculatory disturbance in indomethacin-induced intestinal ulcer. Am. J. Physiol.262, G213–219 (1991).

    Google Scholar 

  95. I. Bjarnason, P. Smethurst, A. Machperson, F. Walker, J. C. McElnay, A. P. Passmore and I. S. Menzies,Glucose and citrate reduce the permeability changes caused by indomethacin in humans. Gastroenterology102, 1546–1550 (1992).

    PubMed  Google Scholar 

  96. P. Del Soldato, D. Foschi, G. Benoni and G. P. Velo,Eazrly and late phases in the formation by anti-inflammatory drugs of intestinal lesions in rats InSide-effects of Anti-inflammatory Drugs Part 2 (Eds. K. D. Rainsford and G. P. Velo) pp. 67–81, MTP Press, Lancaster, Boston, The Hague, London, Dordrecht 1987.

    Google Scholar 

  97. R. T. Schoen and R. J. Vender,Mechanism of non-steroidal anti-inflammatory drug-induced gastric damage. Am. J. Med.86, 449–485 (1989).

    Article  PubMed  Google Scholar 

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Gyires, K. Some of the factors that may mediate or modify the gastrointestinal mucosal damage induced by non-steroidal anti-inflammatory drugs. Agents and Actions 41, 71–79 (1994). https://doi.org/10.1007/BF01986397

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