Radiation-induced changes in intestinal and tissue-nonspecific alkaline phosphatase: implications for recovery after radiation therapy

Am J Surg. 2016 Oct;212(4):602-608. doi: 10.1016/j.amjsurg.2016.06.005. Epub 2016 Jul 18.


Background: Exogenous replacement of depleted enterocyte intestinal alkaline phosphatase (IAP) decreases intestinal injury in models of colitis. We determined whether radiation-induced intestinal injury could be mitigated by oral IAP supplementation and the impact on tissue-nonspecific AP.

Methods: WAG/RjjCmcr rats (n = 5 per group) received lower hemibody irradiation (13 Gy) followed by daily gavage with phosphate-buffered saline or IAP (40 U/kg/d) for 4 days. Real-time polymerase chain reaction, AP activity, and microbiota analysis were performed on intestine. Lipopolysaccharide and cytokine analysis was performed on serum. Data were expressed as a mean ± SEM with P greater than .05 considered significant.

Results: Intestine of irradiated animals demonstrates lower hemibody irradiation and is associated with upregulation of tissue-nonspecific AP, downregulation of IAP, decreased AP activity, and altered composition of the intestinal microbiome.

Conclusions: Supplemental IAP after radiation may be beneficial in mitigating intestinal radiation syndrome as evidenced by improved histologic injury, decreased acute intestinal inflammation, and normalization of intestinal microbiome.

Keywords: Enterocyte; Intestinal alkaline phosphatase; Lipopolysaccharide; Radiation enteritis.

MeSH terms

  • Alkaline Phosphatase / administration & dosage*
  • Alkaline Phosphatase / metabolism*
  • Animals
  • Cytokines / metabolism
  • Down-Regulation
  • Drug Evaluation, Preclinical
  • Gastrointestinal Microbiome*
  • Ileum / enzymology
  • Intestines / enzymology*
  • Intestines / radiation effects
  • Lipopolysaccharides / metabolism
  • Male
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism
  • RNA, Messenger / metabolism
  • Radiotherapy / adverse effects*
  • Radiotherapy Dosage
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation


  • Cytokines
  • Lipopolysaccharides
  • RNA, Messenger
  • Nitric Oxide Synthase
  • Alkaline Phosphatase