The synthetic somatostatin analogue, octreotide, ameliorates acute and delayed intestinal radiation injury.
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.
Wang
J
J
Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, USA.
Zheng
H
H
Sung
C C
CC
Hauer-Jensen
M
M
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
D005765:Gastrointestinal Agents; D011837:Radiation-Protective Agents; D009195:Peroxidase; D015282:Octreotide