Oxygen radicals mediate the final exacerbation of endothelin-1-induced gastric ulcer in rat

We investigated the role of xanthine oxidase-derived oxygen radicals in the development of endothelin-1-induced gastric: ulcer. Mucosal lipid peroxida tion showed a peak 24 h after injection, while gastric mucosal haemodynamic s were fully restored 26 h after endothelin-1 injection. Allopurinol and ox ypurinol, but not superoxide dismutase or catalase, protected the gastric m ucosa 24 h after endothelin-1 injection. Oxypurinol antagonized both the va soconstrictor effect of endothelin-1 and the decrease in gastric ATP. All t reatments on the second day after endothelin-1 injection significantly redu ced gastric mucosal damage. Xanthine oxidase-derived oxygen radicals contri buted largely to the exacerbation but they did not mediate the onset of end othelin-1-induced gastric ulcer. Pretreatment with probucol (500 mg/kg, p.o .) also protected the gastric mucosa from endothelin-1-induced mucosal inju ry by its antioxidant activity. Oxypurinol was gastroprotective through its vasoactive and energy saving actions. The haemodynamic background of endot helin-1-induced gastric ulcer consists of long lasting ischaemia and subseq uent "reperfusion" which may be responsible for the late burst of oxygen ra dicals. (C) 2001 Elsevier Science B.V. All rights reserved.