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Role of xanthine oxidase-derived oxidants and leukocytes in ethanol-induced jejunal mucosal injury

  • Intestinal Disorders, Inflammatory Bowel Disease, And Irritable Bowel Syndrome
  • Published:
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Abstract

Previous reports indicate that intestinal intraluminal ethanol increases mucosal permeability (an index of mucosal injury) and histamine release by mast cells, and that the released histamine plays a role in mediating the increased permeability. In the present study, we investigated whether reactive oxygen metabolites and their major sources (xanthine oxidase and leukocytes) were involved in these ethanol effects. In rabbits, segments of the jejunum were perfused with a control solution or with 6% ethanol. In these segments, mucosal permeability was assessed by determining jejunal clearance of i.v. administered51Cr-ethylenediaminetetraacetate (51Cr-EDTA) and125I-bovine serum albumin (125I-BSA), and mast cell histamine release was estimated from the histamine concentration of the gut effluent. Ethanol increased51Cr-EDTA clearance,125I-BSA clearance, and histamine release. These ethanol effects decreased when the animals were given superoxide dismutase plus catalase (scavenger of O2− and H2O2, respectively), allopurinol, or oxypurinol (xanthine oxidase inhibitors). Administration of a monoclonal antibody (R15.7) against leukocyte adhesion molecule, CD18, inhibited completely the ethanol-induced increased51Cr-EDTA and125I-BSA clearances and histamine release. These and supplementary data suggest that (a) ethanol-induced mucosal injury and mast cell histamine release are mediated primarily by leukocytes, and (b) oxy radicals, especially those generated by xanthine oxidase, mediate these ethanol effects mainly by promoting leukocyte infiltration.

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Authors and Affiliations

  1. From the Gastrointestinal Disease Research Unit, Departments of Medicine and Physiology, Queen's University, Hotel Dieu Hospital, K7L 5G2, Ontario, Canada

    P. K. Dinda PhD, P. Kossev MD, I. T. Beck MD, PhD & M. G. Buell MD, PhD

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  1. P. K. Dinda PhD
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  2. P. Kossev MD
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  3. I. T. Beck MD, PhD
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  4. M. G. Buell MD, PhD
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Dinda, P.K., Kossev, P., Beck, I.T. et al. Role of xanthine oxidase-derived oxidants and leukocytes in ethanol-induced jejunal mucosal injury. Digest Dis Sci 41, 2461–2470 (1996). https://doi.org/10.1007/BF02100144

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  • DOI: https://doi.org/10.1007/BF02100144

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