Xanthine oxidase contributes to lung leak in rats subjected to skin burn

Abstract

We found that rats subjected to thermal skin injury (skin burn) had increased serum xanthine oxidase (XO) activities, increased serum complement activation (decreased serum CH50 levels), increased erythrocyte (RBC) fragility, increased lung neutrophil accumulation, and increased lung leak compared to sham-treated rats. Treatment of rats with allopurinol (an XO inhibitor) not only decreased serum XO activity, but also decreased complement activation, RBC fragility, lung neutrophil accumulation, and lung leak abnormalities in rats subjected to skin burn. We conclude that XO may contribute to acute lung injury and a number of events associated with the development of acute lung leak following skin burn.

Gut-Derived Mesenteric Lymph

“…35 The observation that pulmonary MPO activity increased following thermal injury is consistent with the work of others using similar models of thermal injury. 36,37 Consistent with changes in lung permeability and alveolar apoptosis, lymphatic division prior to thermal injury failed to fully prevent the observed increase in pulmonary MPO accumulation seen with a 40% TBSA burn. One possible explanation for this observation may be that following an ischemic insult and mesenteric reperfusion, circulating neutrophils are primed either by direct interaction with the endothelium of the injured gut or by inflammatory mediators released from the gut into the mesenteric lymphatics or the portal circulation.…”

“…Specifically, increases in lung permeability developed progressively over a 6-hour period and paralleled changes in complement levels. Leff et al 3 and Burton et al 37 found that rats subjected to a 30% second-degree burn had increased serum catalase activity and xanthine oxidase activity, respectively. In a rat intestinal model of ischemia/reperfusion injury, Koike et al 42 demonstrated that following 45 minutes of mesenteric ischemia, intestinal phospholipase A 2 was activated, resulting in neutrophil priming and subsequent lung albumin leak.…”

Role of antioxidants in the treatment of burn lesions

“…25 In the case of allopurinol, it is clear that circulating XO activity has been detected during skin burn, and it represents the major source of free radicals in the serum of burn patients. 26 Allopurinol, and its principal metabolite, oxypurinol, inhibits the enzyme XO, which catalyses the sequential oxidation of hypoxanthine to xanthine and xanthine to uric acid, 27 suggesting the beneficial action of allopurinol in ischaemia reperfusion injury, as occurs in burns. 28 It has been reported that the pineal hormone melatonin may function as a powerful antioxidant, functioning as a scavenger of hydroxyl, peroxyl, and superoxide radicals, 29 in addition to hydrogen peroxide 30 and peroxynitrite -the ugly free radical.…”

Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol

“…Circulating XO activity has also been detected by other groups during thoracoabdominal surgery, intestinal ischemiareperfusion, skin burn, liver transplantation, and hind limb ischemia and reperfusion (Terada et al, 1992;Poggetti et al, 1992;Nielsen et al, 1994;Burton et al, 1995;Pesonen et al, 1998). Circulating XO has also been demonstrated in human ischemia-reperfusion injury, during an aortic cross-clamp procedure (Tan et al, 1995).…”