Xanthine oxidase and neutrophil infiltration in intestinal ischemia

Abstract

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.

Neutrophils Do Not Mediate the Pathophysiological Sequelae of Cryptosporidium parvum Infection in Neonatal Piglets

“…These chemokines are hypothesized to signal neutrophil influx into intestinal mucosa in C. parvum infection. Superoxide has been identified as a key mediator of neutrophil recruitment in intestinal injury induced by reperfusion, irradiation, dextran sodium sulfate, acetic acid, and trinitrobenzene sulfonic acid (13,19,27,37,40,42). Because neutrophil depletion did not attenuate lipid peroxidation of mucosae from C. parvum-infected piglets, we considered the possibility that neutrophil recruitment was mediated by superoxide.…”

Effect of taurine on ulcerogenic response and impaired ulcer healing induced by monochloramine in rat stomachs

“…[1][2][3] It is also known that NH 4 OH interacts with neutrophilderived HClO to generate cytotoxic NH 2 Cl, a powerful oxidant capable of destroying a variety of microorganisms as well as mammalian cell targets. [4][5][6][7][8] We previously reported that NH 4 OH, at a concentration that does not induce gross lesions, damages the mucosa when the stomach is subjected to ischaemia. 11,12 It is generally known that ischaemia activates xanthine oxidase, which is responsible for the production of reactive oxygen metabolites, such as H 2 O 2 , and that the generation of HClO by neutrophils is dependent on the quantity of H 2 O 2 produced.…”

Intra-abdominal hypertension and the abdominal compartment syndrome

“…In our study, we found that ACS resulted in significant increases of MPO, particularly in lung, liver and small intestine. MPO has been shown to be elevated in response to ischemia, but even more so in reperfusion (56). In addition, elevation of MPO has been suggested as a marker of organ damage rather than that of PMN aggregation (57).…”

“…Similar to other compartments, the pressure increases exponentially at a critical volume (55). Further, the pressures, but not the curve shape, are influenced by abdominal wall compliance, with low abdominal wall compliance leading to higher pressures at the same volume (56).…”