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
08/10/2016Pubmed ID
27501776DOI
10.1016/j.amjsurg.2016.06.005Scopus ID
2-s2.0-84991709365 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
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 MFAuthors
John E. Baker PhD Professor in the Surgery department at Medical College of WisconsinDavid 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 PhosphataseAnimals
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