Enteral intestinal alkaline phosphatase administration in newborns decreases iNOS expression in a neonatal necrotizing enterocolitis rat model.

ABSTRACT: To determine if intestinal alkaline phosphatase (IAP) decreases intestinal injury resulting from experimentally induced necrotizing enterocolitis (NEC). We hypothesized that IAP administration prevents the initial development of NEC related intestinal inflammation.Pre- and full-term newborn Sprague-Dawley rat pups were sacrificed on day 1 of life. Pre-term pups were exposed to intermittent hypoxia and formula containing LPS to induce NEC. Select NEC pups were given 40, 4 or 0.4 units/kg of bovine IAP (NEC+IAP40u, IAP4u or IAP0.4u) enterally, once daily. Ileal sections were evaluated by real-time PCR (qRT-PCR) for IAP, iNOS, IL-1?, IL-6, and TNF-? mRNA and immunofluorescence for 3-nitrotyrosine (3-NT).Experimentally induced NEC decreased IAP mRNA expression by 66% (p ? 0.001). IAP supplementation increased IAP mRNA expression to control. Supplemental enteral IAP decreased nitrosative stress as measured by iNOS mRNA expression and 3-NT staining in the NEC stressed pups (p ? 0.01), as well as decreased intestinal TNF-? mRNA expression. In addition, IAP decreased LSP translocation into the serum in the treated pups.We conclude that enterally administered IAP prevents NEC-related intestinal injury and inflammation. Enteral IAP may prove a useful strategy in the prevention of NEC in preterm neonates.

SUBMITTER: Rentea RM 

PROVIDER: S-EPMC5664149 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature