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.

• Authors: Sylvia Gruber, Daniel Hamedinger, Eva Bozsaky, Margret Schmidt, Kathrin Wolfram, Julia Haagen, Bettina Habelt, Martin Puttrich, Wolfgang Dörr
• Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology (Radiother Oncol) Vol. 116 Issue 3 Pg. 404-8 (Sep 2015) ISSN: 1879-0887 [Electronic] Ireland
• PMID: 25890574 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Demulcents
• Hypoxia-Inducible Factor 1, alpha Subunit
• Radiation-Protective Agents
• Pentoxifylline

Topics

• Analysis of Variance
• Animals
• Cell Count
• Demulcents (pharmacology)
• Disease Models, Animal
• Dose Fractionation, Radiation
• Hypoxia (etiology)
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Male
• Mice, Inbred C3H
• Mouth Mucosa (radiation effects)
• Pentoxifylline (pharmacology)
• Radiation-Protective Agents (pharmacology)
• Stomatitis (complications, prevention & control)
• Tongue (radiation effects)