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Gastric cytoprotection: a critical appraisal of the concept, methodology, implications, mechanisms and future research prospects

  • Immunosuppression and Inflammation
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Abstract

Gastric cytoprotection is the property of certain substances, particularly prostaglandins, when used in non-antisecretory doses, to protect the gastric mucosa from becoming inflammed and necrotic on being exposed to noxious agents. An association between alterations in endogenous prostaglandins and gastric mucosal damage induced by a number of drugs has also been observed. The process of adaptive cytoprotection in which mild irritants protect the gastric mucosa against the damaging effects of various necrotizing agents has been shown to be prostaglandin mediated. However, the exact mechanisms underlying this cytoprotective activity have still not been elucidated although a number of hypotheses have been proposed. Recently, thromboxanes, leukotrienes and endogenous sulfhydryls have also been suggested to be involved in the pathogenesis of gastric mucosal damage induced by various necrotizing agents. This review attempts to provide an uptodate appraisal of the concept, methodology, mechanisms and implications of this phenomenon and suggests that prostaglandins and endogenous sulfhydryls may play a significant role in the pathogenesis of gastric ulceration and may serve an important function in maintaining normal gastric mucosal integrity.

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References

  1. A. Robert,Antisecretory, anti-ulcer, cytoprotective and diarrheogenic properties of prostaglandins. InAdvances in Prostaglandins and Thromboxane Research. Vol. 2, pp. 507–520 (Eds B. Samuelsson and R. Paoletti) Raven Press, New York 1976.

    Google Scholar 

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

    PubMed  Google Scholar 

  3. A. Robert, J. E. Nezamis, C. Lancaster and A. J. Hanchar,Cytoprotection by prostaglandins in rats. Gastroenterology77, 433–443 (1979).

    PubMed  Google Scholar 

  4. U. Valcavi, R. Caponi, A. Brambilla, M. Palmira, F. Minoja, F. Bernini, R. Mustani and R. Fumagalli,Gastric antisecretory, anti-ulcer and cytoprotective properties of 9-hydroxy-19, 20-bis-norprostanoic acid in experimental animals. Arzneim. Forsch.32, 657–663 (1982).

    Google Scholar 

  5. P. Del Soldato, S. Daniotti, D. Foschi, G. Toti and V. Rovati,Curative and preventive cytoprotection of PGE 2,pirenzepine and ranitidine in rat ulcers. Drugs Exptl. and Clin. Res.9, 243–247 (1983).

    Google Scholar 

  6. P. Schiantarelli, S. Cadel and G. C. Folco,Gastroprotective effects of morniflumate, an esterified anti-inflammatory drug. Arzneim. Forsch.34, 885–894 (1984).

    Google Scholar 

  7. L. Varin, P. Del Soldato, D. Foschi and M. De Rosa,Further evidences on gastric cytoprotection exerted by pirenzepine. Pharmacol. Res. Commun.16, 653–665 (1984).

    PubMed  Google Scholar 

  8. Y. Isobe, H. Hirose, M. Muramatsu and H. Aihara,Cytoprotective effect of sofalcone in the rat gastric mucosa. Arzneim. Forsch.35, 138–141 (1985).

    Google Scholar 

  9. F. Barzaghi, R. Cesana, F. Delevallee, R. Fournex, A. Nencioni, J. C. Vincent and R. Deraedt,Gastric cytoprotective, antisecretory and anti-ulcer activities of (E)-4-oxo-4-(3,4,5-trimethoxyphenyl)-2-butenoic acid (RU 38086). Arzneim. Forsch.78, 173–180 (1983).

    Google Scholar 

  10. A. Robert, J. R. Schultz, J. E. Nezamis and C. Lancaster,Gastric antisecretory and anti-ulcer properties of PGE 2,15-methyl PGE 2 and 16,16-dimethyl PGE 2:intravenous, oral and intrajejunal administration. Gastroenterology70, 359–370 (1976).

    PubMed  Google Scholar 

  11. A. Robert, J. E. Nezamis, C. Lancaster and A. I. Hanchar,Endogenous formation of prostaglandins prevents gastric necrosis produced by ethanol and thermal injury. Physiologist20, 79 (1977).

    Google Scholar 

  12. A. Robert, C. Lancaster, A. I. Hanchar and J. E. Nezamis,Mild irritants prevent gastric necrosis through prostaglandins formation: histological study. Gastroenterology74, 1086 (1978).

    Google Scholar 

  13. A. Robert, J. E. Nezamis, C. Lancaster, J. P. Davis, S. V. Field and A. Hanchar,Mild irritants prevent gastric necrosis through “adaptive cytoprotection” mediated by prostaglandins. Am. J. Physiol.245, G113-G121 (1983).

    PubMed  Google Scholar 

  14. T. K. Chaudhary and A. Robert,Prevention by mild irritants of gastric necrosis produced in rats by sodium taurocholate. Fed. Proc.37, 303 (1978).

    Google Scholar 

  15. S. J. Konturek, T. Brzozowski, J. Piastucki, T. Radecki, A. Dembinski and A. Dembinska-Kiec,Role of locally generated prostaglandins in adaptive gastric cytoprotection. Dig. Dis. Sc.27, 967–971 (1982).

    Article  Google Scholar 

  16. H. A. Caramichael, L. M. Nelson and R. I. Russel,Cimetidine and prostaglandin: evidence for different modes of action on the rat gastric mucosa. Gastroenterology74, 1229–1232 (1978).

    PubMed  Google Scholar 

  17. A. Robert,Prostaglandins and digestive diseases. InAdvances in Prostaglandins and Thromboxane Research, Vol. 8, pp. 1533–1541 (Eds B. Samuelsson, P. W. Ramwell and R. Paoletti). Raven Press, New York 1980.

    Google Scholar 

  18. S. Szabo, J. S. Trier, A. Brown, J. Schnoor, H. D. Homan and J. C. Bradford,A quantitative method for assessing the extent of experimental gastric erosions and ulcers. J. Pharm. Methods13, 59–66 (1985).

    Article  Google Scholar 

  19. F. Ueda, S. Aratani, K. Mimura, A. Nomura and H. Enomoto,Effect of 2,4-diamino-6-(2,5-dichlorophenyl)-S-triazine maleate (MN-1695) on gastric mucosal damage induced by various necrotizing agents in rats. Arzneim. Forsch.34, 478–484 (1984).

    Google Scholar 

  20. P. H. Guth, D. Aures and G. Paulsen,Topical aspirin plus HCl gastric lesions in the rat. Cytoprotective effect of prostaglandins, cimetidine and probanthine. Gastroenterology76, 88–93 (1979).

    PubMed  Google Scholar 

  21. S. J. Konturek, T. Radecki, T. Brzozowski, J. Piastucki, A. Dembinska-Kiec and A. Zmuda,Gastric cytoprotection by prostaglandins, ranitidine and probanthine in rats. Canad. J. Gastroenterol.16, 7–12 (1981).

    Google Scholar 

  22. J. Hagel, H. Renner, M. Hirsch, G. Weig, B. Kaduk, H. Ruppin and W. Domschke,Gastric cytoprotection by antacids and papavarine in rats. Hepato-Gastroenterol.29, 271–274 (1982).

    Google Scholar 

  23. S. J. Konturek, T. Brzozowski, T. Radecki and J. Piastucki,Gastric cytoprotection by pirenzepine. Role of endogenous prostaglandins. Scand. J. Gastroenterol.17 (Suppl. 72), 255–259 (1982).

    Google Scholar 

  24. A. Robert, C. Lancaster, J. P. Davis, S. O. Field and J. E. Nezamis,Distinction between anti-ulcer effect and cytoprotection. Scand. J. Gastroenterol.19 (Suppl. 101), 69–72 (1984).

    Google Scholar 

  25. J. Puurunen,Effect of prostaglandin E 2,cimetidine and atropine on ethanol induced gastric mucosal damage in the rat. Scand. J. Gastroenterol.15, 485–488 (1980).

    PubMed  Google Scholar 

  26. A. Tarnawski, D. Hollander, H. Gergely and J. Stachura,Comparison of antacids, sucralfate, cimetidine and ranitidine in protection of gastric mucosa against ethanol injury. Gastroenterology34, 1331 (1983).

    Google Scholar 

  27. S. Szabo and K. H. Usadel,Cytoprotection-organoprotection by somatostatin: gastric and hepatic lesions. Experientia38, 254–256 (1982).

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  29. R. K. H. Wong, B. Boedeker, T. M. Hickey, D. S. Wilkinson and L. F. Johnson,Lithium chloride: Protective and antisecretory properties in rats. Gastroenterology87, 362–371 (1984).

    PubMed  Google Scholar 

  30. S. J. Konturek, T. Brzozowski and T. Radecki,Protective action of omeprazole, a benzimidazole derivative on gastric mucosal damage by aspirin and ethanol in rats. Digestion27, 159–164 (1983).

    PubMed  Google Scholar 

  31. B. Kollberg, J. I. Isenberg and C. Johansson,Cytoprotective effect of omeprazole on the rat gastric mucosa. InMechanisms of Mucosal Protection in the Upper Gastrointestinal Tract, pp. 351–355 (Eds A. Allen, G. Flemstrom, A. Garner, W. Silen and L. A. Twinberg) Raven Press, New York 1984.

    Google Scholar 

  32. A. A. Van Kolfschoten, P. Zandberg, L. P. Jager and J. Van Noordwijk,Protection by paracetamol against various gastric irritants in rat. Toxicol. and Appl. Pharmacol.69, 37–42 (1983).

    Article  Google Scholar 

  33. A. Robert,Gastric cytoprotection by sodium salicylate. Prostaglandins21 (Suppl.) 139–146 (1981).

    Article  PubMed  Google Scholar 

  34. S. Malandrino, G. Campagnoli, M. Borsa, R. Guidoboni and G. C. Tonon,Prevention of gastric mucosal lesions in rats by tripotassium dicitratobismuthate. Arzneim. Forsch.34, 30–31 (1984).

    Google Scholar 

  35. D. Hollander, A. Tarnawski, D. Cummings, W. J. Krause, H. Gergely and R. D. Zipser,Cytoprotective action of antacids against alocohol induced gastric mucosal injury. Morphologic, ultrastructural and functional time sequence analysis. Gastroenterology86, 1114 (1984).

    Google Scholar 

  36. A. Tarnawski, D. Hollaner, H. Gergely and J. Stachura,Comparison of antacid, sucralfate, cimetidine, and ranitidine in protection of the gastric mucosa against ethanol injury. Amer. J. Med.79, 19–23 (1985).

    Article  Google Scholar 

  37. 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 

  38. J. Singh,Prostaglandins release from rat stomach following vagal stimulation or administration of acetylcholine. Eur. J. Pharmac.65, 39–48 (1980).

    Article  Google Scholar 

  39. N. K. Boughton-Smith and B. J. R. Whittle,Stimulation and inhibition of prostaglandin formation in the rat gastric mucosa and ileum in vitro by anti-inflammatory agents. Br. J. Pharmac.78, 173–180 (1983).

    Google Scholar 

  40. S. J. Konturek, I. Piastucki, T. Brzozowski, T. Radecki, A. Dembinska-Kiec, A. Zmuda and R. Gryglewski,Role of prostaglandins in formation of aspirin-induced gastric ulcers. Gastroenterology80, 4–9 (1981).

    PubMed  Google Scholar 

  41. B. J. R. Whittle, G. A. Higgs, K. E. Eakins, S. Moncada and J. R. Vane,Selective inhibition of prostaglandin production on inflammatory exudates and gastric mucosa. Nature (London)284, 271–273 (1980).

    Article  Google Scholar 

  42. T. A. Miller,Protective effects of prostaglandins against gastric mucosal damage: current knowledge and proposed mechanisms. Am. J. Physiol.245, G601-G623 (1983).

    PubMed  Google Scholar 

  43. A. Robert,Mechanism of cytoprotection. InIUPHAR 9th International Congress of Pharmacology, London. Proceedings Vol. 4, pp 355–359 (Eds W. Paton, J. Mitchell and P. Turner). The Macmillan Press Ltd., London 1984.

    Google Scholar 

  44. G. L. Kauffman and B. J. R. Whittle,Gastric vascular actions of prostanoids and the dual effect of arachidonic acid. Am. J. Physiol.242, G582-G587 (1982).

    PubMed  Google Scholar 

  45. B. J. R. Whittle, G. L. Kauffman and S. Moncada,Vasoconstriction with thromboxane A 2 induces ulceration of the gastric mucosa. Nature (London)292, 472–474 (1981).

    Article  Google Scholar 

  46. B. J. R. Whittle and S. Moncada,Ulceration induced by an endoperoxide analogue and by indomethacin in the canine stomach. InAdvances in Prostaglandin, Thromboxane and Leukotriene Research, Vol. 12, pp. 373–378 (Eds B. Samuelsson, R. Paoletti and P. Ramwell). Raven Press, New York 1983.

    Google Scholar 

  47. B. J. R. Whittle and S. Moncada,Pharmacological interactions between prostacyclin and thromboxanes. Br. Med. Bull.39, 232–238 (1983).

    PubMed  Google Scholar 

  48. S. J. Konturek, T. Brzozowski, I. Piastucki, T. Radecki and A. Dembinska-Kiec,Role of prostaglandin and thromboxane biosynthesis in gastric necrosis produced by taurocholate and ethanol. Dig. Dis. Sci.28, 154–160 (1983).

    Article  PubMed  Google Scholar 

  49. B. J. R. Whittle,The potentiation of taurocholate induced rat gastric erosions following parenteral administration of cyclooxygenase inhibitors. Br. J. Pharmac.80, 545–551 (1983).

    Google Scholar 

  50. B. J. R. Whittle,Cellular mediators in gastric damage: actions of thromboxane A 2 and its inhibitors. InMechanism of Mucosal Protection in the Upper Gastrointestinal Tract, pp. 295–301 (Eds A. Allen, A. Garner, G. Flemstrom, W. Silen and L. A. Turnberg). Raven Press, New York 1984.

    Google Scholar 

  51. B. J. R. Whittle, N. Oren-Wolman and P. H. Guth,Gastric vasoconstrictor actions of leukotrienes C 4,PGF 2α and the thromboxane mimetic U-46619 on rat submucosal microcirculation in vivo. Am. J. Physiol.248, G580-G586 (1985).

    PubMed  Google Scholar 

  52. B. M. Peskar, K. Lange, U. Hoppe and B. A. Peskar,Ethanol stimulates formation of leukotriene C 4 in rat gastric mucosa. Prostaglandins31, 283–293 (1986).

    Article  PubMed  Google Scholar 

  53. R. G. Pendleton and J. R. Stavorski,Evidence for different leukotriene receptors in gastric mucosa. Eur. J. Pharmac.125, 297–299 (1986).

    Article  Google Scholar 

  54. A. Rosam, J. L. Wallace and B. J. R. Whittle,Potent ulcerogenic actions of platelet activating factor on the stomach. Nature (London)319, 54–56 (1986).

    Article  Google Scholar 

  55. J. L. Wallace and B. J. R. Whittle,Picomole doses of platelet activating factor predispose the gastric mucosa to damage by topical irritants. Prostaglandins31, 989–998 (1986).

    Article  PubMed  Google Scholar 

  56. J. L. Wallace and B. J. R. Whittle,Effects of inhibitors of arachidonic acid metabolism on Paf-induced gastric mucosal necrosis and haemoconcentration. Br. J. Pharmac.89, 415–422 (1986).

    Google Scholar 

  57. T. Mizui and M. Doteuchi,Effect of polyamines on acidified ethanol-induced gastric lesions in rats. Japan J. Pharmacol.33, 939–945 (1983).

    Google Scholar 

  58. E. Ezer,Sodium salicylate is a unique gastrointestinal protective compound in rat. Digestion31, 168 (1985).

    Google Scholar 

  59. D. Dupuy and S. Szabo,Biochemical analysis of sulfhydryls in gastric mucosal protection. Digestion31, 165 (1985).

    Google Scholar 

  60. R. Fumagalli, R. Caponi, A. Corsini, A. Brambilla, M. Palmira, F. Bernini and U. Valcavi,Nonprotein sulfhydryls as possible components of the protective effect of Rosaprostol on the rat gastric mucosa. Prostaglandins29, 467–474 (1985).

    Article  PubMed  Google Scholar 

  61. T. Mizui and M. Doteuchi,Lipid peroxidation: A possible role in gastric damage induced by ethanol in rats. Life. Sci.38, 2163–2167 (1986).

    Article  PubMed  Google Scholar 

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  1. Dept. of Pharmacology & Research Centre, College of Pharmacy, King Saud University, P.O. Box 2457, 11451, Riyadh, Saudi Arabia

    Narayan S. Parmar, Mohammad Tariq & A. M. Ageel

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Parmar, N.S., Tariq, M. & Ageel, A.M. Gastric cytoprotection: a critical appraisal of the concept, methodology, implications, mechanisms and future research prospects. Agents and Actions 22, 114–122 (1987). https://doi.org/10.1007/BF01968826

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