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2015 ; 196
(2
): 235-40
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Intestinal alkaline phosphatase to treat necrotizing enterocolitis
#MMPMID25840489
Biesterveld BE
; Koehler SM
; Heinzerling NP
; Rentea RM
; Fredrich K
; Welak SR
; Gourlay DM
J Surg Res
2015[Jun]; 196
(2
): 235-40
PMID25840489
show ga
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.
|Alkaline Phosphatase/metabolism/*therapeutic use
[MESH]