Ethanol-induced injury to the rat gastric mucosa. Role of neutrophils and xanthine oxidase-derived radicals.
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.
Kvietys
P R
PR
Department of Physiology, Louisiana State University Medical Center, Shreveport.
Twohig
B
B
Danzell
J
J
Specian
R D
RD
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D019817:Benzoic Acid; D002374:Catalase / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology; D000431:Ethanol / Q000633:toxicity*; D005609:Free Radicals; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism*
D001565:Benzoates; D005609:Free Radicals; D000431:Ethanol; D019817:Benzoic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase