Gastroduodenal mucosal defense

Current Opinion in Gastroenterology

Volumn 12, Issue 6, 1996, Pages 503-511

  Wallace, John L ^a   Bell, Cameron J ^b  

^a UNIVERSITY OF CALGARY   (Canada)

^b ROYAL NORTH SHORE HOSPITAL   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

BICARBONATE; NONSTEROID ANTIINFLAMMATORY AGENT;

BLOOD FLOW; DUODENUM MUCOSA; HELICOBACTER PYLORI; MUCUS; PEPTIC ULCER; REVIEW; STOMACH MUCOSA;

EID: 0029842304     PISSN: 02671379     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001574-199611000-00003     Document Type: Review

References (44)

1. Engel E, Guth PH, Nishizaki Y, Kaunitz JD: Barrier function of the gastric mucus gel. Am J Physiol 1995, 269:G994-G999. Simultaneous physical measures offering circumstantial support for the concept that the mucus-bicarbonate layer acts as a barrier to luminal aggressive factors, with exhaustive theoretical modeling of the nature of the barrier.
2. Lichtenberger LM: The hydrophobic barrier properties of gastrointesti nal mucus. Ann Rev Physiol 1995, 57:565-583. A comprehensive review of the composition and properties of the mucus component of the pre-epithelial barrier.
3. Hogan DL, Rapier RC, Dreilinger A, Koss MA, Basuk PM, Weinstein WM, Nyberg LM, Isenberg JI: Duodenal bicarbonate secretion: eradication of Helicobacter pylori and duodenal structure and function in humans. Gastroenterology 1996, 110:705-716. Interesting human studies showing that duodenal bicarbonate secretion is impaired in H. pylori-positive patients with duodenal ulcers and that bicarbonate secretion can be normalized by eradication of H. pylori infection.
4. Ainsworth MA, Koss MA, Hogan DL, Isenberg JI: Higher proximal duode nal bicarbonate secretion is independent of Brunner's glands in rats and rabbits. Gastroenterology 1995, 109:1160-1166. Correlative studies in two species providing data that argue against Brunner's gland as a major source of secreted bicarbonate.
5. Mertz-Nielsen A, Hillingse J, Bukhave K, Rask-Madsen J: Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans. Gut 1996, 38:6-10. Human perfusion studies demonstrating an unexpected stimulatory effect of omeprazole on duodenal mucosal bicarbonate secretion.
6. McGowan CC, Cover TL, Blaser MJ: Helicobacter pylori and gastric acid: biological and therapeutic implications. Gastroenterology 1996, 110:926-938. Thorough review of the impact of H. pylori infection on acid secretion and mechanisms by which H. pylori survives the inhospitable gastric environment.
7. Weigert N, Schaffer K, Schusdziarra V, Classen M, Schepp W: Gastrin secretion from primary cultures of rabbit antrat G cells: stimulation by inflammatory cytokines. Gastroenterology 1996, 110:147-154. Cultured rabbit antrat cells were used to assess the possibility that H. pylori-induced cytokines might mediate the hypergastrinemia associated with the infection, demonstrating a likely role for interleukin-1β and TNF-α, but not interleukin-6 or interleukin-8.
8. Takeuchi K, Takehara K, Kaneko T, Okabe S: Nitric oxide and prostaglandins in regulation of acid secretory response in rat stomach following injury. J Pharmacol Exp Ther 1995, 272:357-363. Carefully designed studies in ex vivo preparations of rat stomach using several cyclooxygenase and NO synthase inhibitors to clarify the mechanism underlying the inhibition of gastric acid secretion seen in response to mucosal injury.
9. Heinemann A, Jocic M, Peskar BM, Holzer P: CCK-evoked hyperemia in rat gastric mucosa involves neural mechanisms and nitric oxide. Am J Physiol 1996, 270:G253-G258. Studies in the perfused stomachs of anaesthetized rats, elucidating the pathway involved in cholecystokinin-induced gastric mucosal hyperemia.
10. Miyake H, Inaba N, Kato S, Takeuchi K: Increased susceptibility of rat gastric mucosa to ulcerogenic stimulation with aging: role of capsaicin-sensitive sensory neurons. Dig Dis Sci 1996, 41:339-345. Studies using rats of various ages assessing the impact of age on the hyperemic response in the chambered stomach to acidified taurocholate.
11. Nishizaki Y, Guth PH, Sternini C, Kaunitz JD: Impairment of the gastric hyperemic response to luminal acid in cirrhotic rats. Am J Physiol 1996, 270:G71-G78. These studies in carbon tetrachloride-induced cirrhosis showed that cirrhosis increased mucosal susceptibility to injurious agents and impaired the mucosal hyperemic response to ethanol and to luminal acid after pentagastrin administration.
12. Ferraz JGP, Wallace JL: Prostaglandins modulate the responsiveness of the gastric microcirculation to sodium nitroprusside in cirrhotic rats. Hepatology 1996, 23:123-129. Elegant studies illustrating the dysregulation of the gastric microcirculation in cirrhoitic rats and demonstrating the complex interactions between vasodilatory mechanisms dependent on cyclic AMP and cyclic GMP.
13. El-Newihi HM, Kanji VK, Mihas AA: Activity of gastric mucosal nitric oxide synthase in portal hypertensive gastropathy. Am J Gastroenterol 1996, 91:535-538. A straightforward clinical study assessing the likelihood that NO produces the gastric vascular lesion of portal hypertensive gastropathy.
14. Asako H, Kubes P, Wallace JL, Wolf RE, Granger DN: Modulation of leukocyte adhesion in rat mesenteric venules by aspirin and salicylate. Gastroenterology 1992, 103:146-152.
15. Asako H, Kubes P, Wallace JL, Gaginella T, Wolf RE, Granger DN: Indomethacin-induced leukocyte adhesion in mesenteric venules: role of lipoxygenase products. Am J Physiol 1992, 262:G903-G908.
16. Kurose I, Wolf R, Miyasaka M, Anderson DC, Granger DN: Microvascular dysfunction induced by nonsteroidal anti-inflammatory drugs: role of leukocytes. Am J Physiol 1996, 270:G363-G369. Aspirin or indomethacin administration resulted in endothelial barrier dysfunction (albumin leakage). This was prevented if leukocyte adherence to the endothelium was prevented by a variety of antibodies against adhesion molecules.
17. Yoshida N, Yoshikawa T, Nakamura Y, Arai M, Matsuyama K, Iinuma S, Yagi N, Naito Y, Miyasaka M, Kondo M: Role of neutrophil-mediated inflammation in aspirin-induced gastric mucosal injury. Dig Dis Sci 1995, 40:2300-2304. Aspirin-induced gastric damage can be prevented by pretreatment of rats with antibodies directed against the CD11/CD18 leukocyte adhesion molecule family or against the endothelial adhesion molecule ICAM-1. This study confirms previous reports using another NSAID (Wallace et al., Am J Physiol 1993; 265:G993-G998) and extends this group's work on aspirin-induced leukocyte adherence in vitro (Yoshida et al., Gastroenterology 1993, 105:715-724).
18. Low J, Grabow D, Sommers C, Wallace J, Lesch M, Finkel M, Schrier D, Metz A, Conroy MC: Cytoprotective effects of Cl-959 in the rat gastric mucosa: modulation of leukocyte adhesion. Gastroenterology 1995, 109:1224-1233. A new anti-inflammatory drug prevents damage to the gastric mucosa induced by NSAIDs or ethanol, apparently through its ability to prevent leukocyte adherence to the vascular endothelium.
19. McCafferty DM, Granger DN, Wallace JL: Indomethacin-induced gastric injury and leukocyte adherence in arthritic versus healthy rats. Gastroenterology 1995, 109:1173-1180. This paper demonstrates that, like humans, arthritic rats are significantly more susceptible to NSAID-induced gastric damage. Arthritic rats exhibited a marked elevation of basal leukocyte adherence in mesenteric venules, apparently due to high levels of ICAM-1 expression. Treatment with anti-ICAM-1 restored leukocyte adherence to normal and prevented NSAID-induced gastric damage.
20. Santucci L Fiorucci S, Giansanti M, Brunori PM, Di Matteo FM, Morelli A: Pentoxifylline prevents indomethacin induced acute gastric mucosal damage in rats: role of tumour necrosis factor alpha. Gut 1994, 35:909-915.
21. Appleyard CB, McCafferty DM, Tigley AW, Swain MG, Wallace JL: Tumor necrosis factor mediation of NSAID-induced gastric damage: role of leukocyte adherence. Am J Physiol 1996, 270:G42-G48. An extension of the work of Santucci et al. (Gut 1994, 35:909-915) demonstrating that TNF-α is released into serum within 30 minutes of NSAID administration and that NSAID-induced gastric injury can be prevented by a variety of inhibitors of TNF-α synthesis or release. This paper also demonstrates that TNF-α may contribute to NSAID-induced mucosal injury independent of effects on leukocyte adherence.
22. Takemura T, Granger DN, Evans DJ, Evans DG, Graham DY, Anderson DC, Wolf RE, Cepinskas G, Kvietys PR: Extract of Helicobacter pylori induces neutrophils to injure endothelial cells and contains antielastase activity. Gastroenterology 1996, 110:21-29. A water extract of H. pylori activates human neutrophils such that when they are added to cultured endothelial cells they injure the latter. This damage is produced through a reactive oxygen metabolite- and elastase-dependent mechanism and requires the adherence of the neutrophils to the endothelium.
23. Wershil BK, Furuta GT, Wang Z-S, Galli SJ: Mast cell-dependent neutrophil and mononuclear cell recruitment in immunoglobulin E-induced gastric reactions. Gastroenterology 1996, 110:1482-1490. Injection of an antibody into the anterior wall of the stomach, followed a day later by systemic administration of the antigen, resulted in significant recruitment into the tissue of neutrophils and mononuclear cells as well as mast cell degranulation. When similar studies were performed in mast cell-deficient mice, the neutrophil-monocyte response was not observed.
24. Rioux KP, Wallace JL: Mast cells do not contribute to nonsteroidal anti- inflammatory drug-induced gastric mucosal injury in rodents. Aliment Pharmacol 1996, 10:173-180. Demonstrates that depletion of mucosal mast cells or increasing mucosal mast cell numbers within the rat stomach did not alter the susceptibility to NSAID-induced gastric damage, nor interfered with the ability of a prostaglandin to protect the stomach. Mast cell-deficient mice showed similar susceptibility to NSAID-induced gastric injury as compared with normal littermates.
25. Kubes P, Wallace JL: Nitric oxide as a mediator of gastrointestinal injury: say it ain't so. Mediators Inflamm 1995, 4:397-405. Comprehensive review of the evidence suggesting that NO primarily functions as a mediator of mucosal defense and challenging the theory that NO causes damage in the gastrointestinal tract.
26. Miller MJS, Grisham MB: Nitric oxide as a mediator of inflammation? You had better better believe itl Mediators Inflamm 1995, 4:387-396. Comprehensive review of the evidence suggesting that NO primarily functions as a mediator of damage and inflammation in the gastrointestinal tract.
27. 2+-mediated damage to rabbit gastric mucosal cells: modulation by nitric oxide. Eur J Pharmacol Environ Toxicol Pharmacol 1995, 293:259-266. Inhibition of NO synthesis results in exacerbation of damage to gastric epithelial cells in vitro caused by calcium ionophore, whereas a NO donor was protective. However, these effects were not attributable to changes in oxidative stress within the cells.
28. McAlindon ME, Muller AF, Filipowicz B, Hawkey CJ: Effect of allopurinol, sulphasalazine, and vitamin C on aspirin induced gastroduodenal injury in human volunteers. Gut 1996, 38:518-524. Aspirin administration increased free radical production by the human gastric mucosa, as measured by chemiluminescence. However, significant reduction of free radical production by allopurinol or sulphasalazine had no significant effect on the extent of gastroduodenal damage. On the other hand, vitamin C had no effect on free radical production but significantly reduced the severity of duodenal damage caused by aspirin.
29. Rutten MJ, Dempsey PJ, Luttropp CA, Hawkey MA, Sheppard BC, Crass RA, Deveney CW, Coffey RJ: Identification of an EGFor TGF-α receptor in primary cultures of guinea pig gastric mucous epithelial cells. Am J Physiol 1996, 270:G604-G612. Demonstration in binding studies of a common EGF or TGF-α receptor in cultured guinea pig gastric epithelial cells, supporting the concept that EGF and TGF-α play a physiologic role in acting as mitogens in these cells.
30. Murayama Y, Miyagawa J-I, Higashiyama S, Kondo S, Yabu M, Isozaki K, Kayanoki Y, Kanayama S, Shinomura Y, Taniguchi N, Matsuzawa Y: Localization of heparin-binding epidermal growth factor-like growth factor in human gastric mucosa. Gastroenterology 1995, 109:1051-1059. In immunohistochemical studies, the recently identified member of the EGF family, HB-EGF, was identified within specific cells within fundic and antral glands, raising the possibility that HB-EGF acts on adjacent gastric epithelial cells as a regulator of proliferation and differentiation.
31. Nakamura M, Oda M, Inoue J, Ito T, Akiba Y, Kitajima M, Tsuchiya M, Ishii H: Effect of basic fibroblast growth factor on reinnervation of gastric microvessels-possible relevance to ulcer recurrence. Dig Dis Sci 1995, 40:1451-1458. In studies of acetic acid-induced ulcers in rat stomachs, treatment with recombinant bFGF hastened ulcer healing and appeared to enhance reinnervation of new vessels within the granulation tissue surrounding the ulcer crater.
32. Hull MA, Cullen DJE, Hudson N, Hawkey CJ: Basic fibroblast growth factor treatment for non-steroidal anti-inflammatory drug associated gastric ulceration. Gut 1995, 37:610-612. Straightforward interventional human pilot study suggesting that treatment with a form of bFGF leads to healing of NSAID-associated gastric ulcers.
33. Kinoshita Y, Nakata H, Hassan S, Asahara M, Kawanami C, Matsushima Y, Naribayashi-Inomoto Y, Ping CY, Min D, Nakamura A, Chiba T: Gene expression of keratinocyte and hepatocyte growth factors during the healing of rat gastric mucosal lesions. Gastroenterology 1995, 109:1068-1077. Hepatocyte growth factor and keratinocyte growth factor mRNA was sought using Northern blot analysis and reverse transcriptase polymerase chain reaction after induction of acute and chronic epithelial injury. Hepatocyte growth factor gene expression was enhanced and keratinocyte growth factor was constantly produced during the process of gastric mucosal healing.
34. Romano M, Meise KS, Suozzo R, Sessa G, Persico M, Coffey RJ: Regional distribution of transforming growth factor-alpha and epidermal growth factor in normal and portal hypertensive gastric mucosa in humans. Dig Dis Sci 1995, 40:263-267. In this clinical study, gastroduodenal mucosal concentrations of EGF and TNF-α were measured in patients with chronic hepatitis and in cirrhotic patients with and without portal hypertensive gastropathy. The authors speculated about the significance of the relative concentrations of the two growth factors and of the lower EGF levels in cirrhotic duodenal mucosa.
35. Tripp MA, Tepperman BL: Effect of nitric oxide on integrity, blood flow and cyclic GMP levels in the rat gastric mucosa: modulation by sialoadenectomy. Br J Pharmacol 1995, 115:344-348. This complex study examined the interrelationships between NO synthase activity, mucosal damage, blood flow, and cyclic GMP levels in control and sialoadenectomized rat stomachs exposed to ethanol. Although EGF reduced mucosal damage, it did not restore depleted NO synthase activity in ethanol-treated, sialoadenectomized rats.
36. Babyatsky MW, Debeaumont M, Thim L, Podolsky DK: Oral trefoil peptides protect against ethanol- and indomethacin-induced gastric injury in rats. Gastroenterology 1996, 110:489-497. Gastric injury induced in rats by either ethanol or indomethacin was significantly attenuated by oral pretreatment with two trefoil peptides, without any effect on gastric pH. This study thus suggested that endogenous trefoil peptides contribute to gastrointestinal mucosal defense.
37. Brzozowski T, Konturek PC, Konturek SJ, Ernst H, Stachura J, Hahn EG: Gastric adaptation to injury by repeated doses of aspirin strengthens mucosal defense against subsequent exposure to various strong irritants in rats. Gut 1995, 37:749-757. This article confirms and extends the findings of a previous report (Wallace et al., Am J Physiol 1995, 268:G134-G138) that repeated administration of aspirin to rats increases the resistance of the gastric mucosa to damage induced by aspirin and also to damage induced by a variety of other ulcerogens. Moreover, this report demonstrates that adaptation to aspirin is accompanied by increased mucosal blood flow and production of EGF and its receptor within the gastric mucosa.
38. Wallace JL, McKnight GW, Bell CJ: Adaptation of rat gastric mucosa to aspirin requires mucosal contact Am J Physiol 1995, 268:G134-G138.
39. Skeljo MV, Cook GA, Elliott SL, Giraud AS, Yeomans ND: Gastric mucosal adaptation to diclofenac injury. Dig Dis Sci 1996, 41:32-39. Adaptation of the rat stomach to repeated diclofenac administration is demonstrated. Resistance develops not only to the damaging effects of this NSAID, but also to other NSAIDs and ethanol. In contrast to a previous report in which adaptation to aspirin was only observed when it was given orally (Wallace et al., Am J Physiol 1995, 268:G134-G138), these authors report that adaptation to diclofenac also occurred when it was administered parenterally.
40. Peskar BM, Lambrecht N, Stroff T, Respondek M, Müller KM: Functional ablation of sensory neurons impairs healing of acute gastric mucosal damage in rats. Dig Dis Sci 1995, 40:2460-2464. Prior ablation of sensory afferent nerves, using systemic capsaicin administration, significantly retarded the healing of ethanol-induced gastric damage in rats. Interestingly, capsaicin treatment had no effect on the extent of acute damage in the corpus but caused a profound increase in damage in the antrum.
41. Conn HO, Poynard T: Corticosteroids and peptic ulcer: meta-analysis of adverse events during steroid therapy. J Intern Med 1994, 236:619-632.
42. Carpani de Kaski M, Rentsch R, Levi S, Hodgson HJF: Corticosteroids reduce regenerative repair of epithelium in experimental gastric ulcers. Gut 1995, 37:613-616. Gastric ulcers in rats treated with indomethacin or prednisone were found to be larger than those in rats treated with the vehicle. However, it is impossible to determine if the drugs delayed gastric ulcer healing, increased the size of the initial ulcer, or both, because the rats were given the drugs prior to as well as after ulcer induction.
43. Elliott SN, McKnight W, Cirino G, Wallace JL: A nitric oxide-releasing nonsteroidal anti-inflammatory drug accelerates gastric ulcer healing in rats. Gastroenterology 1995, 109:524-530. This paper demonstrates the ability of a NO-releasing NSAID derivative to accelerate healing of gastric ulcers in the rat. This effect appeared to be attributable to the NO released from this compound, because healing of ulcers could also be observed, in a dose-dependent manner, with another NO donor (glyceryl trinitrate).
44. Penney AG, Malcontenti-Wilson C, O'Brien PE, Andrews FJ: NSAID-induced delay in gastric ulcer healing is not associated with decreased epithelial cell proliferation in rats. Dig Dis Sci 1995, 40:2684-2693. In rats with acetic acid-induced gastric ulcers, mucosal regeneration was measured and epithelial cell proliferation assessed in animals treated for 2 weeks with aspirin or indomethacin. Both agents delayed ulcer healing and impaired mucosal regeneration but did not retard epithelial cell proliferation.