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.

c_2">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 m>Pm> greater than .05 considered significant.

c_3">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.

c_4">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.