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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

Date

08/10/2016

Pubmed ID

27501776

DOI

10.1016/j.amjsurg.2016.06.005

Scopus ID

2-s2.0-84991709365 (requires institutional sign-in at Scopus site)   9 Citations

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.

Author List

Rentea RM, Lam V, Biesterveld B, Fredrich KM, Callison J, Fish BL, Baker JE, Komorowski R, Gourlay DM, Otterson MF

Authors

John E. Baker PhD Professor in the Surgery department at Medical College of Wisconsin
David M. Gourlay MD Chief, Professor in the Surgery department at Medical College of Wisconsin
Mary F. Otterson MD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

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