Enteral glutamine supplementation and dexamethasone attenuate the local intestinal damage in rats with experimental necrotizing enterocolitis

The pathogenesis of necrotizing enterocolitis (NEC) presumptively is due to an inappropriate intestinal epithelial immunologic response of immature gut to luminal stimuli. Glutamine is essential for intestinal crypt cell proliferation and enhances the cellular response to growth factors. We aimed to test the hypothesis that the supplementation of enteral feedings with glutamine may stimulate an immature intestine and decrease the intestinal inflammatory change in NEC. Immediately after birth, the neonatal rats were weighed and randomized into one of four treatment groups. Group 1 consisted of rats whom were breast-fed. Group 2 (NEC group) consisted of neonates whom were fed with a special rodent formula. Rats in groups 3 and 4 were fed in a similar fashion to those in group 2, and glutamine 0.3 mg/kg per day and dexamethasone 0.5 mg/kg per day were added to their formula, respectively. The neonatal rats were weighed and killed on day 4: the last 4 cm of terminal ileum was harvested for morphological studies and detection of nitrite and nitrate levels in tissue. The animals in the NEC group showed various degrees of inflammatory changes similar to clinical NEC. The inflammatory changes of the intestine appeared to be attenuated in both glutamine- and steroid-treated animals compared to those in the NEC group. Only steroid treatment decreased the tissue levels of these nitrogen oxides that were increased in rats in the NEC group. We herein provide evidence that maturational agents such as glutamine and dexametasone can attenuate the local intestinal inflammatory damage in experimental NEC. These findings support the hypothesis that the gut immaturity in premature infants represents a risk factor for NEC.