title: The synthetic somatostatin analogue, octreotide, ameliorates acute and delayed intestinal radiation injury.
abstract: OBJECTIVE
  Reducing intraluminal proteolytic activity attenuates intestinal radiation toxicity. This study assessed whether pharmacological inhibition of exocrine pancreatic secretion protects against early and delayed radiation enteropathy in a preclinical rat model.
  
  
  METHODS
  Rat ileum was sham-irradiated or exposed to 16 once-daily 4.2 Gy fractions of X-radiation. Vehicle or somatostatin analogue (octreotide, 2 microg/kg/hr) were administered from 2 days prior to 10 days after the end of irradiation. Mucosal injury was monitored noninvasively by assessment of granulocyte transmigration. Radiation injury was assessed at 2 weeks (early phase) and 26 weeks (chronic phase) using quantitative histopathology, immunohistochemistry, and morphometry.
  
  
  RESULTS
  Octreotide decreased granulocyte transmigration (p<0.0006), reduced accumulation of myeloperoxidase-positive cells at 2 weeks (p = 0.0002), attenuated structural injury at 2 weeks (p = 0.04) and 26 weeks (p = 0.02), preserved mucosal surface area at 2 weeks (p = 0.0008) and 26 weeks p = 0.0008), and reduced intestinal wall thickening at 26 weeks (p = 0.002). Octreotide did not affect granulocyte transmigration, histology, or mucosal surface area in sham-irradiated controls.
  
  
  CONCLUSIONS
  These results demonstrate the importance of consequential mechanisms in the pathogenesis of chronic radiation enteropathy. Short-term octreotide administration ameliorates acute radiation-induced mucosal injury, as well as chronic structural changes, and should be subject to further preclinical and clinical testing.
authors.affiliation: Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Zheng
authors.forename: C C
authors.initials: CC
authors.lastname: Sung
authors.forename: M
authors.initials: M
authors.lastname: Hauer-Jensen
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000528:radiation effects; D004334:Drug Administration Schedule; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006098:Granulocytes / Q000528:radiation effects; D007410:Intestinal Diseases / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D015282:Octreotide / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005765:Gastrointestinal Agents; D011837:Radiation-Protective Agents; D009195:Peroxidase; D015282:Octreotide