Intestinal alkaline phosphatase to treat necrotizing enterocolitis. J Surg Res 2015 Jun 15;196(2):235-40
Date
04/05/2015Pubmed ID
25840489Pubmed Central ID
PMC4578817DOI
10.1016/j.jss.2015.02.030Scopus ID
2-s2.0-84930384574 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
BACKGROUND: Intestinal alkaline phosphatase (IAP) activity is decreased in necrotizing enterocolitis (NEC), and IAP supplementation prevents NEC development. It is not known if IAP given after NEC onset can reverse the course of the disease. We hypothesized that enteral IAP given after NEC induction would not reverse intestinal injury.
MATERIALS AND METHODS: NEC was induced in Sprague-Dawley pups by delivery preterm followed by formula feedings with lipopolysaccharide (LPS) and hypoxia exposure and continued up to 4 d. IAP was added to feeds on day 2 until being sacrificed on day 4. NEC severity was scored based on hematoxylin and eosin-stained terminal ileum sections, and AP activity was measured using a colorimetric assay. IAP and interleukin-6 expression were measured using real time polymerase chain reaction.
RESULTS: NEC pups' alkaline phosphatase (AP) activity was decreased to 0.18 U/mg compared with controls of 0.57 U/mg (P < 0.01). Discontinuation of LPS and hypoxia after 2 d increased AP activity to 0.36 U/mg (P < 0.01). IAP supplementation in matched groups did not impact total AP activity or expression. Discontinuing LPS and hypoxia after NEC onset improved intestinal injury scores to 1.14 compared with continued stressors, score 2.25 (P < 0.01). IAP supplementation decreased interleukin-6 expression two-fold (P < 0.05), though did not reverse NEC intestinal damage (P = 0.5).
CONCLUSIONS: This is the first work to demonstrate that removing the source of NEC improves intestinal damage and increases AP activity. When used as a rescue treatment, IAP decreased intestinal inflammation though did not impact injury making it likely that IAP is best used preventatively to those neonates at risk.
Author List
Biesterveld BE, Koehler SM, Heinzerling NP, Rentea RM, Fredrich K, Welak SR, Gourlay DMAuthors
David M. Gourlay MD Chief, Professor in the Surgery department at Medical College of WisconsinScott R. Welak MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Alkaline PhosphataseAnimals
Animals, Newborn
Drug Evaluation, Preclinical
Enterocolitis, Necrotizing
Female
Interleukin-6
Intestines
Polymerase Chain Reaction
Pregnancy
Rats, Sprague-Dawley
