Xanthine oxidase and neutrophil infiltration in intestinal ischemia.
A growing body of experimental data indicates that reactive oxygen metabolites such as superoxide, hydrogen peroxide, and hydroxyl radical may mediate the mucosal injury produced by reperfusion of ischemic intestine. Xanthine oxidase has been proposed as the primary source of these reduced O2 species because pretreatment with xanthine oxidase inhibitors such as allopurinol or pterin aldehyde prevent postischemic mucosal injury. Another potential source of oxygen radicals is the inflammatory neutrophil. To ascertain whether neutrophils could play a role in the pathogenesis of ischemia-reperfusion injury in the small bowel we examined the effect of ischemia and reperfusion on neutrophil infiltration and tissue levels of reduced glutathione, superoxide dismutase, and catalase. Our studies demonstrate that reperfusion of ischemic intestines results in a dramatic increase (1,800%) in neutrophil infiltration and a concurrent loss of reduced glutathione and superoxide dismutase of 60 and 30%, respectively. Catalase activity was unaffected by ischemia-reperfusion. Pretreatment with allopurinol or administration of superoxide dismutase prevented the influx of neutrophils and retarded the drop in reduced glutathione levels. These results suggest a relationship among xanthine oxidase-generated oxy radicals, neutrophil extravasation, and mucosal damage. We propose that ischemia and reperfusion results in xanthine oxidase-generated, superoxide-dependent accumulation of inflammatory neutrophils in the mucosa where neutrophil-derived reactive oxygen metabolites mediate and/or exacerbate intestinal injury.
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002415:Cats; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000201:enzymology* / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D010100:Oxygen / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism*
D005609:Free Radicals; D000493:Allopurinol; D009195:Peroxidase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D005978:Glutathione; D010100:Oxygen