Enteral intestinal alkaline phosphatase administration in newborns decreases iNOS expression in a neonatal necrotizing enterocolitis rat model. J Pediatr Surg 2013 Jan;48(1):124-8
Date
01/22/2013Pubmed ID
23331804Pubmed Central ID
PMC5664149DOI
10.1016/j.jpedsurg.2012.10.026Scopus ID
2-s2.0-84872391628 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
PURPOSE: 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.
METHODS: 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-1β, IL-6, and TNF-α mRNA and immunofluorescence for 3-nitrotyrosine (3-NT).
RESULTS: 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-α mRNA expression. In addition, IAP decreased LSP translocation into the serum in the treated pups.
CONCLUSIONS: 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.
Author List
Rentea RM, Liedel JL, Fredrich K, Pritchard K Jr, Oldham KT, Simpson PM, Gourlay DMAuthors
David M. Gourlay MD Chief, Professor in the Surgery department at Medical College of WisconsinKirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Alkaline PhosphataseAnimals
Anti-Inflammatory Agents
Biomarkers
Dose-Response Relationship, Drug
Drug Administration Schedule
Enteral Nutrition
Enterocolitis, Necrotizing
Fluorescent Antibody Technique
Ileum
Lipopolysaccharides
Nitric Oxide Synthase Type II
Rats
Rats, Sprague-Dawley
Real-Time Polymerase Chain Reaction
Tumor Necrosis Factor-alpha