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

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. administered 51Cr-ethylenediaminetetraacetate (51Cr-EDTA) and 125I-bovine serum albumin (125I-BSA), and mast cell histamine release was estimated from the histamine concentration of the gut effluent. Ethanol increased 51Cr-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 increased 51Cr-EDTA and 125I-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.

Effect of Alcohol Consumption on the Gut

“…This is supported by the observation that this damage could be prevented by the administration of inhibitors of the adhesion of leukocytes and/or by free radical scavengers [17] .…”

“…Perfusion of segments of jejunum with 6% ethanol suggested that ethanol mediated some of the effects on the mucosa and GI permeability through promoting leukocyte infi ltration and release of reactive oxygen species and histamine from mast cells [10,17] . This is supported by the observation that this damage could be prevented by the administration of inhibitors of the adhesion of leukocytes and/or by free radical scavengers [17] .…”

Epidermal growth factor increases tissue antioxidant enzyme activities in ethanol-induced gastric injury in rat

“…Recent studies suggest that oxidative tissue damage could be a key mechanism in the deleterious effect of ethanol on GI tract (6,10). Rapid and strong venoconstriction occurs within a few minutes of ethanol application, followed by vigorous arteriolar dilatation (14).…”

Ethanol-Related Gastric Mucosal Damage: Evidence of a Free Radical-Mediated Mechanism and Beneficial Effect of Oral Supplementation with Bionormalizer, a Novel Natural Antioxidant

“…Although on an experimental basis, Bionormalizer seems to be able to suppress oxygen radicals in cell-free systems such as the Fenton reaction, hydrogen peroxide hypochloride or horseradish peroxidase system as well as the xanthine-xanthine oxidase system [24, 25]. On the other hand, the toxic effect of ethanol may partly involve synthesis of reactive oxygen species independent of the xanthine oxidase activation, such as occurs in neutrophil recruitment [11, 26]. Accordingly, mucosal inflammatory infiltrate was significantly reduced in Bionormalizer-treated subjects.…”