Intestinal alkaline phosphatase to treat necrotizing enterocolitis

Area of Science:

• Neonatal research
• Gastroenterology
• Biochemistry

Background:

• Necrotizing enterocolitis (NEC) is associated with decreased intestinal alkaline phosphatase (IAP) activity.
• IAP supplementation is known to prevent NEC development.
• The efficacy of IAP as a rescue therapy after NEC onset remains unknown.

Purpose of the Study:

• To investigate if enteral IAP administration after NEC induction can reverse intestinal injury in a neonatal model.
• To determine the impact of IAP supplementation on intestinal damage, alkaline phosphatase activity, and inflammatory markers in NEC.

Main Methods:

• NEC was induced in preterm Sprague-Dawley rat pups via formula, lipopolysaccharide (LPS), and hypoxia.
• Enteral IAP was administered from day 2 of NEC induction until sacrifice on day 4.
• Intestinal injury was scored, and alkaline phosphatase (AP) activity, IAP, and interleukin-6 expression were quantified.

Main Results:

• NEC pups exhibited significantly reduced AP activity compared to controls.
• Discontinuing LPS and hypoxia post-NEC onset improved intestinal injury scores and increased AP activity.
• IAP supplementation did not alter total AP activity but decreased interleukin-6 expression, without reversing intestinal damage.

Conclusions:

• Removing NEC stressors post-onset improves intestinal damage and increases AP activity.
• Enteral IAP as a rescue treatment reduces intestinal inflammation but does not reverse established NEC injury.
• IAP is likely most effective as a preventative measure for neonates at risk of NEC.