Intestinal alkaline phosphatase administration in newborns is protective of gut barrier function in a neonatal necrotizing enterocolitis rat model

Rebecca M. Rentea, Jennifer L. Liedel, Scott R. Welak, Laura D. Cassidy, Alan N. Mayer, Kirkwood A. Pritchard, Keith T. Oldham, David M. Gourlay

Research output: Contribution to journalArticle

30 Scopus citations

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 4U, 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.

Original languageEnglish (US)
Pages (from-to)1135-1142
Number of pages8
JournalJournal of Pediatric Surgery
Volume47
Issue number6
DOIs
StatePublished - Jun 2012

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Keywords

  • Dose response
  • Gut barrier
  • Intestinal alkaline phosphatase
  • Necrotizing enterocolitis
  • Tight junction

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

Cite this

Rentea, R. M., Liedel, J. L., Welak, S. R., Cassidy, L. D., Mayer, A. N., Pritchard, K. A., Oldham, K. T., & Gourlay, D. M. (2012). Intestinal alkaline phosphatase administration in newborns is protective of gut barrier function in a neonatal necrotizing enterocolitis rat model. Journal of Pediatric Surgery, 47(6), 1135-1142. https://doi.org/10.1016/j.jpedsurg.2012.03.018