Rebecca M Rentea1, Vy Lam2, Ben Biesterveld3, Katherine M Fredrich2, Jennifer Callison4, Brian L Fish5, John E Baker2, Richard Komorowski6, David M Gourlay7, Mary F Otterson8. 1. Department of Surgery, Children's Mercy Hospital, 2401 Gillham Road, Kansas City, MO 64108, USA. Electronic address: rrentea@cmh.edu. 2. Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA. 3. Department of Surgery, University of Michigan, Ann Arbor, MI, USA. 4. Department of Surgery, Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI, USA. 5. Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA. 6. Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI, USA. 7. Division of Pediatric Surgery, Medical College of Wisconsin, Children's Hospital of Wisconsin, Children's Research Institute, Milwaukee, WI, USA. 8. Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
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.
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.