XO may be important in tissue injury mediated by reactive oxygen species. Here we studied the role of XO in a rat model of PAF-induced intestinal necrosis. Anesthetized young S.D. rats were injected with PAF (1.5 or 2.8 μg/kg, iv), and the activities of XD and XO in intestinal epithelia as well as whole intestinal tissue were assayed. XO is localized by histochemistry. Intestinal myeloperoxidase (an index of PMN influx) and nitric oxide synthase (NOS) activities were also assayed. We found: (1) PAF dose dependently elevated XO activity, particularly in the ileum, as early as 15-30 min. The total intestinal XD+XO activity was not changed. XO/(XO+XD) (20% in controls), more than tripled at 60 min after high dose PAF. (2) XO is localized mainly in the epithelial cells, except the crypts. Activation occurred predominantly in the ileal epithelia. (3) Allopurinol (XO inhibitor) did not reduce PAF-induced PMN sequestration, but reversed PAF-induced constitutive NOS (cNOS) suppression, and alleviated PAF-induced intestinal necrosis. (4) PAF induced-XO activation was abolished by PMN depletion. Thus, PAF induces XD to XO conversion in ileal epithelia, which is mediated via PMN activation, and XO plays a major role in PAF-induced tissue injury.
|Original language||English (US)|
|State||Published - 1997|
ASJC Scopus subject areas
- Molecular Biology