Radiation-induced changes in intestinal and tissue-nonspecific alkaline phosphatase: implications for recovery after radiation therapy - 12/10/16
, Vy Lam, Ph.D. b, Ben Biesterveld, M.D. c, Katherine M. Fredrich, B.S. d, Jennifer Callison, B.S. e, Brian L. Fish, B.S. f, John E. Baker, M.D. b, Richard Komorowski, M.D. g, David M. Gourlay, M.D. h, Mary F. Otterson, M.D. b, dAbstract |
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.
Le texte complet de cet article est disponible en PDF.Keywords : Intestinal alkaline phosphatase, Radiation enteritis, Enterocyte, Lipopolysaccharide
Plan
| Contributions: R.M.R., J.E.B., D.M.G., and M.F.O are responsible for conception and design of the research; R.M.R., V.Y., B.B., K.M.F., J.C., and B.L.F. performed the experiments; R.M.R. and M.F.O. analyzed the data; R.M.R., J.E.B., D.M.G., and M.F.O. interpreted the results of the experiments; R.M.R. prepared the figures; R.M.R., V.L., J.E.B., D.M.G., and M.F.O. drafted the manuscript; R.M.R., J.E.B., R.K., D.M.G., and M.F.O. edited and revised the manuscript; and R.M.R., J.E.B., D.M.G., and M.F.O. approved the final version of the manuscript. |
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| Supported by the Clinical and Translational Science Institute of Southeast Wisconsin Award 1-UL1-RR031973 and Clinical and Translational Science Award Grant 8UL1TR00005 and the Digestive Disease Center of the Medical College of Wisconsin. |
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| The authors declare no conflicts of interest. |
Vol 212 - N° 4
P. 602-608 - octobre 2016 Retour au numéro
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