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 language | English (US) |
---|---|
Pages (from-to) | 1135-1142 |
Number of pages | 8 |
Journal | Journal of Pediatric Surgery |
Volume | 47 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2012 |
Keywords
- Dose response
- Gut barrier
- Intestinal alkaline phosphatase
- Necrotizing enterocolitis
- Tight junction
ASJC Scopus subject areas
- Surgery
- Pediatrics, Perinatology, and Child Health