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The protective role of intestinal alkaline phosphatase in necrotizing enterocolitis. J Surg Res 2010 Sep;163(1):79-85

Date

07/06/2010

Pubmed ID

20599220

DOI

10.1016/j.jss.2010.04.048

Scopus ID

2-s2.0-77955927943   32 Citations

Abstract

BACKGROUND: Enterocytes produce intestinal alkaline phosphatase (iAP), which detoxifies lipopolysaccharide (LPS), a mediator in necrotizing enterocolitis (NEC) pathogenesis. We hypothesize that aberrant expression or function of iAP contributes to the pathogenesis of NEC.

MATERIALS AND METHODS: Newborn Sprague Dawley rat pups were divided into three main groups. Control pups were breast fed, while two groups were exposed to intermittent hypoxia, LPS, and formula feeding for 4 d to induce NEC. Bovine iAP, with and without the presence of LPS, was administered orally to one of the NEC groups. The intestine was harvested and used to detect alkaline phosphatase (AP) activity and protein expression. Terminal ileum sections were used to grade intestinal injury and stained for AP. Comparisons were made with adult rat duodenum.

RESULTS: Compared with adult rats, control pups expressed significantly less AP protein but had 2-fold higher AP activity. NEC pup AP activity was significantly decreased compared to controls (P < or = 0.05), which paralleled both the AP protein expression and immunofluorescence assay results. Following iAP administration, immunofluorescence, protein expression, and activity of AP were significantly increased compared with NEC pups without iAP supplementation. All NEC pups had intestinal injury grades > or = 2 on a 4-point scale, while control and iAP-treated pups had grades < 0.25 (P < 0.001).

CONCLUSIONS: Enteral administration of iAP to rat pups with experimental NEC increased AP activity levels to that of controls, and appears to protect the intestine. This opens up a new area of study in NEC pathophysiology as well as a potential novel treatment strategy to prevent the development of NEC.

Author List

Whitehouse JS, Riggle KM, Purpi DP, Mayer AN, Pritchard KA Jr, Oldham KT, Gourlay DM

Authors

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




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

Alkaline Phosphatase
Animals
Animals, Newborn
Cattle
Enterocolitis, Necrotizing
Ileum
Isoenzymes
Rats
Rats, Sprague-Dawley
jenkins-FCD Prod-409 d1e206b0be345926047b0d9c353c78a4cce4058b