title: Enteral intestinal alkaline phosphatase administration in newborns decreases iNOS expression in a neonatal necrotizing enterocolitis rat model.
abstract: OBJECTIVE
  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.
authors: Medical College of Wisconsin, Children's Hospital of Wisconsin/Children's Research Institute, Milwaukee, WI 53226, USA. rrentea@mcw.edu
authors: Rebecca M
authors: RM
authors: Rentea
authors: Jennifer L
authors: JL
authors: Liedel
authors: Katherine
authors: K
authors: Fredrich
authors: Kirkwood
authors: K
authors: Pritchard
authors: Keith T
authors: KT
authors: Oldham
authors: Pippa M
authors: PM
authors: Simpson
authors: David M
authors: DM
authors: Gourlay
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004750:Enteral Nutrition; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy* / Q000201:enzymology; D005455:Fluorescent Antibody Technique; D007082:Ileum / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000469:Alkaline Phosphatase