title: Radiation-induced changes in intestinal and tissue-nonspecific alkaline phosphatase: implications for recovery after radiation therapy.
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.
authors: Department of Surgery, Children's Mercy Hospital, 2401 Gillham Road, Kansas City, MO 64108, USA. Electronic address: rrentea@cmh.edu.
authors: Rebecca M
authors: RM
authors: Rentea
authors: Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Vy
authors: V
authors: Lam
authors: Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
authors: Ben
authors: B
authors: Biesterveld
authors: Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Katherine M
authors: KM
authors: Fredrich
authors: Department of Surgery, Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI, USA.
authors: Jennifer
authors: J
authors: Callison
authors: Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Brian L
authors: BL
authors: Fish
authors: Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: John E
authors: JE
authors: Baker
authors: Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Richard
authors: R
authors: Komorowski
authors: Division of Pediatric Surgery, Medical College of Wisconsin, Children's Hospital of Wisconsin, Children's Research Institute, Milwaukee, WI, USA.
authors: David M
authors: DM
authors: Gourlay
authors: Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Mary F
authors: MF
authors: Otterson
mesh_terms: D000469:Alkaline Phosphatase / Q000008:administration & dosage* / Q000378:metabolism*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D004353:Drug Evaluation, Preclinical; D000069196:Gastrointestinal Microbiome; D007082:Ileum / Q000201:enzymology; D007422:Intestines / Q000201:enzymology* / Q000528:radiation effects; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011878:Radiotherapy / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D000469:Alkaline Phosphatase
keywords: Enterocyte; Intestinal alkaline phosphatase; Lipopolysaccharide; Radiation enteritis