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

Abstract

Purpose: 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 and Materials: Rat ileum was sham-irradiated or exposed to 16 once-daily 4.2 Gy fractions of X-radiation. Vehicle or somatostatin analogue (octreotide, 2 μg/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. Conclusion: 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.