The Effect of Enteral Allopurinol Suspension on the Intestinal Mucosal Injury and Survival Rate in the Induced Mesenteric Ischemia of White Rats

The sequelae of ischemic injury to the intestine are potentially devastating to the patient. And it has also been implicated as playing a major role in the development of necrotizing enterocolitis, a major cause of morbidity and mortality in the newborn.

Many studies have demonstrated that allopurinol can reduce reperfusion injury after ischemia. But they have limited clinical significance because the data in those studies were produced using parenteral allopurinol unavailable for use in patients or enteral allopurinol at high-doses that is not tolerated and has prohibitive side effects.

This study evaluated the protective effects of clinically used doses of enteral allopurinol in rats with intestinal ischemia. One-hundred sixteen Sprague-Dawley rats(180~250g) received allopurinol(1mg/100g) suspensin water(experimental group) or tap water(controls) for 1 week. Four rats(2 treated with allopurinol and 2 controls) were used to identify histologic finding of small bowel mucosa. Sixteen rats(each 8 of allopurinol-treated and control) were used to measure serum uric acid levels to document systemic effects of allopurinol. Ninty-six rats were subjected to superior mesenteric vessels occlusion for 20, 30 or 40 min to produce ischemic injury to the intestine. Segmental small bowel resections were performed in 12 control rats and 12 allopurinol-treated rats before and after reperfusion to identify histopathologic evidence of reperfusion injury. And the remaining seventy-two rats(each 36 of allopurinol-treated and control) were observed for mortality(death within 7 days) after reperfusion.

Serum uric acid was decreased from 3.70±1.62mg/dl in controls to 2.41±0.75mg/dl in allopurinol-treated group. Mucosal injury severity was not different significantly among the periods of mesenteric vascular occlusion. But after 30 min of reperfusion, severity of mucosal injury in controls was significantly aggrevated and in allopurinol-treated groups was not different from injury severity of ischemic period. The lethal time 50% (LT5O) in controls was between 30 and 40 min of ischemia. There was reduction in mortality after allopurinol pretreatment in the presently available form and dose with 20, 30 or 40 min of ischemia. And the reduction of mortality in allopurinol-treated groups was distinguishable with LT5O of ischemic period.

This study has demonstrated that protective effects of allopurinol to mucosal injury caused by mesenteric ischemia can be achieved with enteral doses that are not likely to cause intolerable side effects and agonizing stress with daily gastric lavage chronically.