Abstract
Cytoprotection is the term originally introduced into gastrointestinal (GI) pa-thophysiology by Robert to describe the unique feature of prostaglandins (PG) to prevent acute necrotic lesions of the GI mucosa at nonantisecretory doses. This phenomenon has been studied extensively, primarily in experimental animals, and two major categories of cytoprotection have been identified: direct cytoprotection induced by PG administered exogenously, and adaptive cytoprotection elicited by mild irritants and probably mediated by endogenous PG. Since histologic examination of the PG-protected mucosa reveals that only deep hem-orrhagic necrosis is prevented — the surface epithelium becomes damaged — the term cytoprotection has been questioned. Although the surface epithelium cells are lost, the prevention by PG of deep hemorrhagic necrosis and of damage to the cells around the mucous neck allows for rapid cell migration and restitution of the integrity of surface epithelium and almost complete preservation of organ functions. The use of organoprotection (e. g., gastroprotection) is now recommended and is reviewed in this chapter.
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Braquet P, Etienne A, Mencia-Muerta J-M, et al: The role of platelet activating factor in gastrointestinal ulcerations. Eur J. Pharmacol 1988. Study indicating that PAF may contribute to gastric damage in endotoxine shock and restraint stress and that PAF antagonists prevent PAF-and endotoxin-induced mucosal damage.
Gregory H: Isolation and structure of urogastrone and its relationship to epidermal growth factor. Nature (Lond) 257:325–328, 1975. Early review describing the structure, origin, and biological action of EGF and urogastrone.
Guth PH: Mucosal coating agents and other nonantisecretory agents. Are they cytoprotective? Dig Dis Sci 32:647–654, 1987. Recent review of gastroprotective drugs and substances and their mechanisms of action.
Hollander D, Tarnawski A, Gergely H, Zipser RD: Sucralfate protection of the gastric mucosa against ethanol-induced injury: A prostaglandin mediated process? Scan. J. Gastroenterol. 19(Suppl 101):97–102, 1984. First demonstration that protective action of sucralfate is dependent (at least in part) on release of endogenous mucosal prostaglandins.
Hollander D, Tarnawski A: Protection against alcohol-induced gastric mucosal injury by aluminum-containing compounds — sucralfate, antacids and aluminum sulfate. Scand J. Gastroenterol. 21(Suppl 125):165–169, 1986. Paper discussing the role of aluminum-containing compounds in protection of the gastric mucosa against injury.
Konturek SJ: Gastroprotection by antisecretory and non-antisecretory agents. Klin Wochenschr 64: 24–27, 1986. Review of gastroprotection induced by agents inhibiting and noninhibiting gastric acid secretion.
Konturek SJ: Role of epidermal growth factor in gastroprotection and ulcer healing. Scand J Gastroenterol 23:249–254, 1988. Review article on the involvement of EGF in gastroprotection and ulcer healing.
Konturek SJ, Brzozowski T, Drozdowicz D, et al: Role of leukotrienes in acute gastric lesions induced by ethanol, taurocholate, aspirin, platelet-activating factor and stress in rats. Dig Dis Sci 33:806–813, 1988. Study showing deleterious effects of LTC4 and PAF on the gastric mucosa and their prevention by LTC4 receptor antagonists.
Konturek SJ, Brzozowski T, Piastucki I, et al: Role of prostaglandin and thromboxane biosynthesis in gastric necrosis produced by taurocholate and ethanol. Dig Dis Sci 28:154–160, 1983. Study showing that gastric mucosa generates Tx and that Specific Tx synthesis inhibitor (OKY 1581) prevent taurocholate-induced mucosal damage.
Konturek SJ, Brzozowski T, Radecki T et al: Cytoprotective effects of gastrointestinal hormones, in Miyoshi A (ed): Gut Peptides and hormones, Tokyo, Biomed Res Found 1982, p. 411.
Konturek SJ, Dembinski A, Warzecha Z et al: Role of epidermal growth factor in healing of chronic gastroduodenal ulcers in rats. Gastroenterology 94:1300–1307, 1988. Study showing that endogenous EGF secreted by salivary and duodenal glands plays an important role in healing of chronic gastroduodenal ulcers via stimulating mucosal growth.
Konturek SJ, Kitler ME, Brzozowski T, et al: Gastric protection by meciadanol. A new synthetic flavonoid-inhibiting histidine decarboxylase. Dig Dis Sci 31:847–852, 1986. This paper provides an evidence that the inhibition of histamine formation by suppressing histidine decarboxylase activity in gastric mucosa prevents acute gastric lesions induced by ethanol or aspirin.
Konturek SJ, Pawlik W: Physiology and pharmacology of prostaglandins. Dig Dis Sci 31(suppl):6S–19S, 1986. Review of physiological role and pharmacological effects of prostaglandins.
Konturek SJ, Radecki T, Brzozowski T, et al: Antiulcer and gastroprotective effects of Solon, a synthetic flavonoid derivative of sophoradin. Role of endogenous prostaglandins. Eur J Pharmacol 125:185–192, 1986. Study on the gastroprotection induced by Solon and its mechanisms.
Konturek SJ, Radecki T, Brzozowski T, et al: Gastric cytoprotection by epidermal growth factor. Role of endogenous prostaglandins and DNA synthesis. Gastroenterology 81:438–443, 1981. First study showing that EGF protects gastric mucosa against aspirin damage via PG-indepen-dent mechanism.
Konturek SJ, Radecki T, Piastucki I, et al: Gastroprotection by colloidal bismuth subcitrate (De-Nol) and sucralfate. Role of endogenous prostaglandins. Gut 28:201–205, 1987. Study showing that both De-Nol and Sucralfate prevent the formation of acute gastric lesions induced by various irritants and that it may be attributable, at least in part, to an increase in the mucosal generation of PGs.
Kusterer K, Rohr G, Schwedes V: Gastric mucosal protection by somatostatin. Klin Wochenschr 64 (suppl VII):97–99, 1986. Study showing that somatostatin protects the gastric mucosa against various irritants.
Lacy ER, Itoh S: Microscopic analysis of ethanol damage to rat gastric mucosa after treatment with a prostaglandin. Gastroenterology 83:619–625, 1982. Study showing that prostaglandins do not prevent the destruction of surface epithelial cells by absolute ethanol, questioning the concept of the cytoprotection.
Olsen PS, Poulsen SS, Kirkegaard P, et al: Role of submandibular saliva and epidermal growth factor in gastric cytoprotection. Gastroenterology 87:103–108, 1984. Study demonstrating gastroprotective effect of endogenous and exogenous EGF against cysteamine-induced mucosal injury.
Peskar BM, Lange K, Hoppe U, et al: Ethanol stimulates formation of leukotriene C4 in rat gastric mucosa. Prostaglandins 31:283–293, 1986. Study showing deleterious effect of LTC4 generated in ethanol-treated gastric mucosa and possible prevention of this damage by LT inhibitors.
Robert A: Cytoprotection by prostaglandins. Gastroenterology 77:761–767, 1979. Proposition of the concept of direct cytoprotection induced by exogenous PG and adaptive cytoprotection by mild irritants acting via releasing endogenous PG.
Robert A, Nezamis JE, Lancaster C, et al: Cytoprotection by prostaglandins in rats: prevention of gastric necrosis produced by alcohol, HC1, NaOH, hypertonic NaCl and thermal injury. Gastroenterology 83:619–625, 1982. First study showing macroscopic prevention by prostaglandins of acute gastric mucosal damage by various necrotizing substances.
Silen W: Gastric mucosal defense and repair, in Johnson LR (ed): Physiology of the Gastrointestinal Tract, ed. 2. New York, Raven, 1987, p. 1055. Review chapter on the mucosal defense mechanism against various noxious agents, emphasizing the importance of rapid restitution of mucosal cells in the recovery of the mucosa from the damage.
Szabo S, Trier JS, Frankel PW: Sulfhydryl compounds may mediate gastric cytoprotection. Science 214:200–202, 1981. Study showing that endogenous and exogenous sulfhydryl compounds may be initiators of gastroprotection.
Takeuchi K, Johnson LR: Effect of cell proliferation and loss on aspirin-induced gastric damage in the rat. Am J Physiol 243:G468–G643, 1982. Study indicating that gastrin may contribute to the gastroprotection against aspirin-induced mucosal damage by a mechanism involving stimulation of mucosal growth and epithelium proliferation.
Takeuchi K, Johnson LR: Pentagastrin protects against stress ulcerations in rats. Gastroenterology 76:324–327, 1979. First study demonstrating that pentagastrin protects against stress ulceration, possibly through stimulation of growth of gastric mucosa.
Tarnawski A, Hollander D, Gergely H, Stachura J: Comparison of antacid, sucralfate, cimetidine and ranitidine in protection of the gastric mucosa against ethanol injury. Am. J. hied. 79(2C): 19–23, 1985. Study demonstrating that sucralfate and antacid protect the gastric mucosa against alcohol injury while H2 blockers, cimetidine and ranitidine not only do not offer protection but in fact may increase alcohol-induced damage.
Tarnawski A, Hollander D, Krause WJ, Stachura J, Gergely H: Does sucralfate affect the normal gastric mucosa? Histologic, ultrastructural and functional assessment in the rat. Gastroenterology 90:893–906, 1986. Experimental study demonstrating interaction of sucralfate with normal gastric mucosa in rats in a manner increasing its defensive capabilities.
Tarnawski A, Hollander D, Stachura J, Mach T, Bogdal J: Effect of sucralfate on the normal human gastric mucosa. Endoscopic, histologie and ultrastructural assessment. Scand. J. Gastroenterol. 22(suppl 127):111–123, 1987. First endoscopie, histologie and ultrastructural study demonstrating interaction of sucralfate with normal human gastric mucosa.
Wallace JL, Whittle BJR: Profile of gastrointestinal damage induced by platelet activating factor. Prostaglandins 32:137–141, 1986. Study describing the deleterious effects of PAF on the gastrointestinal mucosa.
Whittle BJR, Vane JR: Prostanoids as regulators of gastrointestinal function, in Johnson LR (ed): Physiology of the Gastrointestinal Tract, ed 2. New York, Raven, 1987, p. 143. Extensive review of endogenous arachidonate products involved in gastric damage (Tx, LT) and protection (PG).
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© 1989 Plenum Publishing Corporation
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Konturek, S.J., Konturek, J.W. (1989). Gastroprotection by Nonprostaglandin Substances. In: Hollander, D., Tarnawski, A.S. (eds) Gastric Cytoprotection. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5697-4_11
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DOI: https://doi.org/10.1007/978-1-4684-5697-4_11
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