Gastroenterology

Gastroenterology

Volume 98, Issue 4, April 1990, Pages 909-920
Gastroenterology

Ethanol-induced injury to the rat gastric mucosa: Role of neutrophils and xanthine oxidase-derived radicals

https://doi.org/10.1016/0016-5085(90)90015-SGet rights and content

Abstract

Ethanol-induced gastric mucosal injury closely resembles an inflammatory response. Thus, in vivo and in vitro experimental models were used to assess whether ethanol is proinflammatory in concentrations likely to be encountered by the gastric mucosa during acute intoxication. Perfusing the rat gastric lumen with progressively increasing concentrations of ethanol (10%, 20%, and 30%) resulted in a dose-dependent increase in 51Cr-ethylenediaminetetraacetic acid clearance from blood-to-gastric lumen. Rendering the animals neutropenic (with antineutrophil serum) ameliorated the ethanol-induced mucosal injury; the degree of protection was directly related to the severity of neutropenia. Neither superoxide dismutase, catalase, nor sodium benzoate offered any protection against ethanol-induced injury, indicating that neither superoxide anion, hydrogen peroxide, nor the hydroxyl radical is involved. To assess further whether ethanol could exert proinflammatory effects an in vitro model consisting of cultured bovine microvascular endothelial cells and isolated human neutrophils was used. Ethanol at concentrations of 1.0%–4.0% (but not at 0.1%–0.5%) increased neutrophil adherence to endothelial cells and enhanced neutrophil-mediated endothelial cell injury. We conclude that ethanol is proinflammatory at concentrations that may be achieved in the gastric mucosa during acute intoxication. The ethanol-induced, neutrophil-mediated cell injury does not appear to involve oxy radicals.

References (43)

  • MB Grisham et al.

    A comparative study of neutrophil purification and function

    J Immunol Methods

    (1985)
  • SM Smith et al.

    Gastric mucosal injury in the rat. Role of iron and xanthine oxidase

    Gastroenterology

    (1987)
  • M Itoh et al.

    Role of oxygen-derived free radicals in hemorrhagic shock-induced gastric lesions in the rat

    Gastroenterology

    (1985)
  • FA Green et al.

    Ethanol enhanced transmembrane generation of arachidonic acid and activation of the 5-lipoxygenase pathway in human leukocytes

    Biochem Biophys Res Comm

    (1986)
  • SJ Gluckman et al.

    Effect of acute alcohol intoxication on granulocyte mobilization and kinetics

    Blood

    (1978)
  • JM Harlan

    Leukocyte-endothelial interactions

    Blood

    (1985)
  • MS Smith et al.

    Gastric ulcers: role of oxygen radicals

    Crit Care Med

    (1988)
  • M Guslandi

    Effect of ethanol on the gastric mucosa

    Dig Dis

    (1987)
  • WY Chey

    Alcohol and gastric mucosa

    Digestion

    (1972)
  • VP Dinoso et al.

    Ultrastructural changes of the canine gastric mucosa after topical application of graded concentrations of ethanol

    Dig Dis

    (1976)
  • HM Maling et al.

    Blood alcohol levels, triglyceride fatty livers, and pathologic changes in rats after single large doses of alcohol

  • Cited by (186)

    • Activation of AMPK/mTOR-driven autophagy and inhibition of NLRP3 inflammasome by saxagliptin ameliorate ethanol-induced gastric mucosal damage

      2021, Life Sciences
      Citation Excerpt :

      The present set of experiments concur with the regimen characterized in previous studies of ethanol-induced gastric injury [21,22]. Notably, the 70% ethanol dose has been selected for the induction of gastric mucosal damage since it provokes reliable induction of gastric mucosal injury and histopathological changes in rats [28]. The aforementioned dose also allows the monitoring of the in vivo cellular and molecular changes such as apoptosis, inflammation, and autophagy [29].

    • ANKRD22 Drives Rapid Proliferation of Lgr5<sup>+</sup> Cells and Acts as a Promising Therapeutic Target in Gastric Mucosal Injury

      2021, Cellular and Molecular Gastroenterology and Hepatology
      Citation Excerpt :

      Therefore, ANKRD22 may be an ideal target for the development of novel gastric mucosal repair agents owing to its effects in promoting the proliferation of EPCs and reducing inflammation. Neutrophil infiltration represents the acute inflammatory response in ethanol-induced gastric mucosal injury.37 Furthermore, we identified both in vivo and in vitro conditions in which AV023 promotes the proliferation of the Lgr5+ gastric EPCs and exerts anti-inflammatory effects, particularly aiding in the reduction of neutrophilic infiltration.

    View all citing articles on Scopus

    This work was supported by a Biomedical Research Support Grant, 2 507 RR05822-09, from the National Institutes of Health.

    View full text