The Effect of Allopurinol via Breast-Feeding Route on the Intestinal Ischemia-Reperfusion Injury of Neonatal Rats

Hypoxia is one of the most common major stress to which a neonate exposed, and subclinical ischemic/hypoxic insults to the intestine has been implicated as playing a major role in the development of NEC. The exact mechanism leading to mucosal injury due to mesenteric ischemia-reperfusion have not been fully elucidated, yet there is an increasing body of evidence to suggest a role for xanthine oxidase(XO)- derived reactive oxygen metabolites. Allopurinol has repeatedly been demonstrated to be effctive in decreasing reperfusion injury.

This study was designed to evaluate the protective effects of allopurinol via breast-feeding to suckling rats, in the setting of ischemia and reperfusion.

One-hundred forty Sprague-Dawley rat pups(one-week-old) received breast-feeding whose lactating mothers were bred on standard chow with allopurinol(2mg/100g) suspension water(expermental group) or tap water(control group) for 1 week. Eight rats(each 4 of experimentals and controls) were used to identify histologic finding of small bowel mucosa. Twelve rats(each 6 of experimentals and controls) were used to measure serum uric acid levels. Ninety-six rats (each 48 of experimentals and controls) were subjected to superior mesenteric vessels occlusion for 5, 10 or 20 min. to produce ischemic injury to the intestine. Segmental small bowel resections were performed in each 24 rats of control group and experimental group before and after reperfusiort to histopathologic evidence of reperfusion injury. And the remaining 72 rats(each 36 of experimentals and controls) were observed for mortality after IRI for 1 month.

Serum uric acid 1.93±0.64mg/dl of experimentals was significantly lower than 7.32±1.18mg/dl of controls(p<0.005). Bowel injury severity was more severe on longer period of mesenteric vascular occlusion in experimentals and controls. Mucosal injury severity was not different significantly between experimentals and controls with same period of mesenteric vascular occlusion, but after 30 min of reperfusion, severity of mucosal injury in experimentals was attenuated than in controls, especially in the 5 min and 10 min occlusion of mesenteric vessels. All of death occurred in 3 days after IRI, and mortality was decreased from 69.4% in controls to 52.8% in experimental groups. Mortality was increased in case of longer period occlusion of mesenteric vessels but not significant statistically.

These results indicate that it is ability to transfer the effect of allopurinol to suckling rats via breast-feeding routes and the protective effects of allopurinol increases the survival rate after IRI.