Local hypoxia in oral mucosa (mouse) during daily fractionated irradiation - Effect of pentoxifylline.

Abstract

PURPOSE: A significant reduction of radiation-induced oral mucositis by systemic application of pentoxifylline has been demonstrated in a mouse tongue model. However, the underlying mechanisms remain unclear. The present study focuses on the development of local hypoxia in mouse tongue during daily fractionated irradiation and a potential modulation by pentoxifylline. MATERIALS AND METHODS: Daily fractionated irradiation with 5×3Gy/week (days 0-4, 7-11) was given to the snouts of mice. Groups of 3 animals per day were sacrificed between day 0 and 14. Pentoxifylline (15mg/kg, s.c.) was administered daily from day -5 to the day before the mice were sacrificed. The expression of intrinsic hypoxia markers HIF-1α and GLUT1 in the epithelium of the lower tongue surface was analysed by immunohistochemistry in 3 animals per day; the percentage of positive epithelial cells and the staining intensity were analysed as endpoints. RESULTS: Compared to untreated control tissue, fractionated irradiation resulted in a progressive increase in the expression of both hypoxia markers. This effect was significantly reduced by pentoxifylline. CONCLUSION: An early onset of local hypoxia occurs during fractionated irradiation in mouse tongue epithelium. The effect is markedly reduced by the mucoprotective agent pentoxifylline, suggesting a mucositis-promoting role of hypoxia; this, however, deserves further investigation.