Agents and Actions

, Volume 22, Issue 1–2, pp 114–122 | Cite as

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

  • Narayan S. Parmar
  • Mohammad Tariq
  • A. M. Ageel
Immunosuppression and Inflammation

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.

Keywords

Prostaglandin Gastric Mucosa Gastric Ulceration Critical Appraisal Sulfhydryl 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [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. [2]
    A. Robert,Cytoprotection by prostaglandins. Gastroenterology77, 761–767 (1979).PubMedGoogle Scholar
  3. [3]
    A. Robert, J. E. Nezamis, C. Lancaster and A. J. Hanchar,Cytoprotection by prostaglandins in rats. Gastroenterology77, 433–443 (1979).PubMedGoogle Scholar
  4. [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. [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. [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. [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).PubMedGoogle Scholar
  8. [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. [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. [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).PubMedGoogle Scholar
  11. [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. [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. [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).PubMedGoogle Scholar
  14. [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. [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).CrossRefGoogle Scholar
  16. [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).PubMedGoogle Scholar
  17. [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. [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).CrossRefGoogle Scholar
  19. [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. [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).PubMedGoogle Scholar
  21. [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. [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. [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. [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. [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).PubMedGoogle Scholar
  26. [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. [27]
    S. Szabo and K. H. Usadel,Cytoprotection-organoprotection by somatostatin: gastric and hepatic lesions. Experientia38, 254–256 (1982).PubMedGoogle Scholar
  28. [28]
    S. Szabo, J. S. Trier and P. W. Frankel,Sulfhydryl compounds may mediate gastric cytoprotection. Science214, 200–202 (1981).PubMedGoogle Scholar
  29. [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).PubMedGoogle Scholar
  30. [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).PubMedGoogle Scholar
  31. [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. [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).CrossRefGoogle Scholar
  33. [33]
    A. Robert,Gastric cytoprotection by sodium salicylate. Prostaglandins21 (Suppl.) 139–146 (1981).CrossRefPubMedGoogle Scholar
  34. [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. [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. [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).CrossRefGoogle Scholar
  37. [37]
    I. Szelenyi and K. Brune,Possible role of sulfhydryls in mucosal protection induced by aluminium hydroxide. Dig. Dis. Sci.31, 1207–1210 (1986).CrossRefPubMedGoogle Scholar
  38. [38]
    J. Singh,Prostaglandins release from rat stomach following vagal stimulation or administration of acetylcholine. Eur. J. Pharmac.65, 39–48 (1980).CrossRefGoogle Scholar
  39. [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. [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).PubMedGoogle Scholar
  41. [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).CrossRefGoogle Scholar
  42. [42]
    T. A. Miller,Protective effects of prostaglandins against gastric mucosal damage: current knowledge and proposed mechanisms. Am. J. Physiol.245, G601-G623 (1983).PubMedGoogle Scholar
  43. [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. [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).PubMedGoogle Scholar
  45. [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).CrossRefGoogle Scholar
  46. [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. [47]
    B. J. R. Whittle and S. Moncada,Pharmacological interactions between prostacyclin and thromboxanes. Br. Med. Bull.39, 232–238 (1983).PubMedGoogle Scholar
  48. [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).CrossRefPubMedGoogle Scholar
  49. [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. [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. [51]
    B. J. R. Whittle, N. Oren-Wolman and P. H. Guth,Gastric vasoconstrictor actions of leukotrienes C 4,PGF and the thromboxane mimetic U-46619 on rat submucosal microcirculation in vivo. Am. J. Physiol.248, G580-G586 (1985).PubMedGoogle Scholar
  52. [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).CrossRefPubMedGoogle Scholar
  53. [53]
    R. G. Pendleton and J. R. Stavorski,Evidence for different leukotriene receptors in gastric mucosa. Eur. J. Pharmac.125, 297–299 (1986).CrossRefGoogle Scholar
  54. [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).CrossRefGoogle Scholar
  55. [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).CrossRefPubMedGoogle Scholar
  56. [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. [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. [58]
    E. Ezer,Sodium salicylate is a unique gastrointestinal protective compound in rat. Digestion31, 168 (1985).Google Scholar
  59. [59]
    D. Dupuy and S. Szabo,Biochemical analysis of sulfhydryls in gastric mucosal protection. Digestion31, 165 (1985).Google Scholar
  60. [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).CrossRefPubMedGoogle Scholar
  61. [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).CrossRefPubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag 1987

Authors and Affiliations

  • Narayan S. Parmar
    • 1
  • Mohammad Tariq
    • 1
  • A. M. Ageel
    • 1
  1. 1.Dept. of Pharmacology & Research Centre, College of PharmacyKing Saud UniversityRiyadhSaudi Arabia

Personalised recommendations