Role of xanthine oxidase-derived oxidants and leukocytes in ethanol-induced jejunal mucosal injury.
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.
Dinda
P K
PK
Gastrointestinal Disease Research Unit, Department of Medicine, Queen's University, Hotel Dieu Hospital, Ontario, Canada.
Kossev
P
P
Beck
I T
IT
Buell
M G
MG
D000222:Adaptation, Physiological; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000431:Ethanol / Q000009:adverse effects*; D006636:Histamine Release / Q000502:physiology; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000503:physiopathology; D007583:Jejunum / Q000187:drug effects* / Q000503:physiopathology; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D010117:Oxypurinol / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000502:physiology; D014969:Xanthine Oxidase / Q000378:metabolism*
D017382:Reactive Oxygen Species; D000431:Ethanol; D000493:Allopurinol; D014969:Xanthine Oxidase; D010117:Oxypurinol