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

Document Type

Article

Publication Date

10-1-2016

Identifier

DOI: 10.1016/j.amjsurg.2016.06.005

Abstract

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.

Journal Title

American journal of surgery

Volume

212

Issue

4

First Page

602

Last Page

608

MeSH Keywords

Alkaline Phosphatase; Animals; Cytokines; Down-Regulation; Drug Evaluation, Preclinical; Gastrointestinal Microbiome; Ileum; Intestines; Lipopolysaccharides; Male; Nitric Oxide Synthase; RNA, Messenger; Radiotherapy; Radiotherapy Dosage; Rats; Real-Time Polymerase Chain Reaction; Up-Regulation

Keywords

Enterocyte; Intestinal alkaline phosphatase; Lipopolysaccharide; Radiation enteritis

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