The protective role of intestinal alkaline phosphatase in necrotizing enterocolitis. J Surg Res 2010 Sep;163(1):79-85
Date
07/06/2010Pubmed ID
20599220DOI
10.1016/j.jss.2010.04.048Scopus ID
2-s2.0-77955927943 36 CitationsAbstract
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 DMAuthors
David M. Gourlay MD Chief, Professor in the Surgery department at Medical College of WisconsinKeith 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 PhosphataseAnimals
Animals, Newborn
Cattle
Enterocolitis, Necrotizing
Ileum
Isoenzymes
Rats
Rats, Sprague-Dawley
