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

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• 作者：Rebecca M. Rentea ; M.D.^a ; ^{rrentea@cmh.edu" class="auth_mail" title="E-mail the corresponding author} ; 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 ; ^d
• 关键词：Intestinal alkaline phosphatase ; Radiation enteritis ; Enterocyte ; Lipopolysaccharide
• 刊名：The American Journal of Surgery
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：212
• 期：4
• 页码：602-608
• 全文大小：886 K

文摘

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.