The synthetic somatostatin analogue, octreotide, ameliorates acute and delayed intestinal radiation injury

Purpose: Reducing intraluminal proteolytic activity attenuates intestinal r adiation toxicity. This study assessed whether pharmacological inhibition o f exocrine pancreatic secretion protects against early and delayed radiatio n enteropathy in a preclinical rat model. Methods and Materials: Rat ileum was sham-irradiated or exposed to 16 once- daily 4.2 Gy fractions of X-radiation. Vehicle or somatostatin analogue (oc treotide, 2 mu g/kg/hr) were administered from 2 days prior to 10 days afte r the end of irradiation. Mucosal injury was monitored noninvasively by ass essment of granulocyte transmigration. Radiation injury was assessed at 2 w eeks (early phase) and 26 weeks (chronic phase) using quantitative histopat hology, immunohistochemistry, and morphometry. Results: Octreotide decreased granulocyte transmigration (p < 0.0006), redu ced 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), O ctreotide did not affect granulocyte transmigration, histology, or mucosal surface area in sham-irradiated controls. Conclusion: These results demonstrate the importance of consequential mecha nisms in the pathogenesis of chronic radiation enteropathy. Short-term octr eotide administration ameliorates acute radiation-induced mucosal injury, a s well as chronic structural changes, and should be subject to further prec linical and clinical testing. (C) 1999 Elsevier Science Inc.