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Intestinal alkaline phosphatase administration in newborns is protective of gut barrier function in a neonatal necrotizing enterocolitis rat model. J Pediatr Surg 2012 Jun;47(6):1135-42

Date

06/19/2012

Pubmed ID

22703783

DOI

10.1016/j.jpedsurg.2012.03.018

Abstract

BACKGROUND: Previously, we have shown that supplementation of intestinal alkaline phosphatase (IAP) decreased severity of necrotizing enterocolitis (NEC)-associated intestinal injury. We hypothesized that IAP administration is protective of intestinal epithelial barrier function in a dose-dependent manner.

METHODS: Control rat pups were vaginally delivered and breast-fed. Premature rats were divided into 4 groups: formula fed with lipopolysaccharide and hypoxia (NEC) or additional daily bovine IAP 40, 4, or 0.4 U/kg (NEC + IAP 40 U, IAP 4 U, or IAP 0.4 U).

RESULTS: Necrotizing enterocolitis is associated with decreased IAP protein expression and activity. Supplemental IAP increases IAP activity in intestinal homogenates and decreased NEC injury score in a dose-dependent manner. Intestinal injury as measured by fluorescein isothiocyanate-dextran flux from ileal loops showed increased permeability vs control, but supplemental IAP reversed this. Tight junction proteins claudin-1, claudin-3, occludin, and zonula occludin 1 were elevated in the NEC and IAP-treated groups with differences in expression patterns. No differences in messenger RNA levels were observed on postinjury day 3. Intestinal alkaline phosphatase administration decreases intestinal NEC injury in a dose-dependent manner.

CONCLUSION: Early enteral supplemental IAP may reduce NEC-related injury and may be useful for preserving the intestinal epithelial barrier function.

Author List

Rentea RM, Liedel JL, Welak SR, Cassidy LD, Mayer AN, Pritchard KA Jr, Oldham KT, Gourlay DM

Authors

Laura Cassidy PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin
David M. Gourlay MD Chief, Professor in the Surgery department at Medical College of Wisconsin
Keith T. Oldham MD Professor in the Surgery department at Medical College of Wisconsin
Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin
Scott R. Welak MD Assistant Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Administration, Oral
Alkaline Phosphatase
Animals
Animals, Newborn
Claudin-1
Claudin-3
Claudins
Dextrans
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Enterocolitis, Necrotizing
Fluorescein-5-isothiocyanate
Gene Expression Regulation
Ileum
Intestinal Absorption
Intestinal Mucosa
Lipopolysaccharides
Membrane Proteins
Models, Animal
Permeability
Rats
Rats, Sprague-Dawley
Real-Time Polymerase Chain Reaction
Tight Junctions
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a