Gruber Sylvia, Bozsaky Eva, Roitinger Eva, Schwarz Karoline, Schmidt Margret, Dörr Wolfgang
Applied and Translational Radiobiology, Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Medical University/AKH Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Dept. Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
Strahlenther Onkol. 2017 Jun;193(6):499-507. doi: 10.1007/s00066-017-1119-8. Epub 2017 Mar 3.
Early inflammation is a major factor of mucosal reactions to radiotherapy. Pentoxifylline administration resulted in a significant amelioration of radiation-induced oral mucositis in the mouse tongue model. The underlying mechanisms may be related to the immunomodulatory properties of the drug. The present study hence focuses on the manifestation of early inflammatory changes in mouse tongue during daily fractionated irradiation and their potential modulation by pentoxifylline.
Daily fractionated irradiation with 5 fractions of 3 Gy/week (days 0-4, 7-11) was given to the snouts of mice. Groups of 3 animals per day were euthanized every second day between day 0 and 14. Pentoxifylline (15 mg/kg, s. c.) was administered daily from day 5 to the day before sacrifice. The expression of the inflammatory proteins TNFα, NF-κB, and IL-1β were analysed.
Fractionated irradiation increased the expression of all inflammatory markers. Pentoxifylline significantly reduced the expression of TNFα and IL-1β, but not NF-κB.
Early inflammation, as indicated by the expression of the inflammatory markers TNFα, NF-κB, and IL-1β, is an essential component of early radiogenic oral mucositis. Pentoxifylline differentially modulated the expression of different inflammatory markers. The mucoprotective effect of pentoxifylline does not appear to be based on modulation of NF-κB-associated inflammation.
早期炎症是黏膜对放疗产生反应的主要因素。在小鼠舌部模型中，给予己酮可可碱可显著改善放射性口腔黏膜炎。其潜在机制可能与该药物的免疫调节特性有关。因此，本研究聚焦于小鼠舌部在每日分次照射期间早期炎症变化的表现以及己酮可可碱对其的潜在调节作用。
对小鼠口鼻部进行每日分次照射，每周5次，每次3 Gy（第0 - 4天、第7 - 11天）。在第0天至第14天期间，每隔一天对每组3只动物实施安乐死。从第5天至处死前一天，每天给予己酮可可碱（15毫克/千克，皮下注射）。分析炎症蛋白TNFα、NF - κB和IL - 1β的表达。
分次照射增加了所有炎症标志物的表达。己酮可可碱显著降低了TNFα和IL - 1β的表达，但未降低NF - κB的表达。
炎症标志物TNFα、NF - κB和IL - 1β的表达所表明的早期炎症是放射性口腔黏膜炎早期的一个重要组成部分。己酮可可碱对不同炎症标志物的表达有不同的调节作用。己酮可可碱的黏膜保护作用似乎并非基于对NF - κB相关炎症的调节。
