The stable nitroxide tempol facilitates salivary gland protection during head and neck irradiation in a mouse model
The stable nitroxide tempol facilitates salivary gland protection during head and neck irradiation in a mouse model
复制标题
DOI：
10.1158/1078-0432.ccr-03-0194
复制
发表时间：
2004-03-01
影响因子：
11.5
通讯作者：
Baum, BJ
中科院分区：
文献类型：
--
作者：
Vitolo, JM;Cotrim, AP;Baum, BJ
目的：放射治疗是治疗大多数头颈部癌症的常用方法。长期放射引起的唾液输出减少是这些患者治疗后发病率的重要原因。本研究的目的是测试已建立的辐射保护剂--稳定自由基Tempol(4-hydroxy-2，2，6，6-tetramethylpiperidine-N-oxyl)，预防辐射引起的小鼠唾液功能减退的能力。实验设计：C3H小鼠头部暴露于一定范围的单一辐射剂量，并有或没有ip。治疗前10min静脉注射坦波尔275 mg/kg。8周后评估唾液腺输出量。结果：在该模型中，放疗引起唾液流量呈剂量依赖性减少。单用坦波尔治疗可显著减少辐射引起的唾液功能减退。Tempoll与口鼻屏蔽剂的组合在15Gy时显示出基本完全的辐射防护，在17.5Gy时显示出类似于75%的防护。结论：本研究首次证明了Tempoll对C3H小鼠唾液腺的显著辐射防护作用。
Purpose: Radiotherapy is commonly used to treat a majority of patients with head and neck cancers. The long-term radiation-induced reduction of saliva output significantly contributes to the posttreatment morbidity experienced by these patients. The purpose of this study was to test the ability of the stable-free radical Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), an established radioprotector, to prevent radiation-induced salivary hypofunction in mice.Experimental Design: The heads of C3H mice were exposed to a range of single radiation doses with or without an i.p. injection of 275 mg/kg Tempol 10 min before treatment. Salivary gland output was assessed 8 weeks postirradiation.Results: Radiation caused a dose-dependent reduction in salivary flow in this model. Tempol treatment alone significantly reduced radiation-induced salivary hypofunction. The combination of Tempol with mouth/nose shielding showed essentially complete radiation protection at 15 Gy and similar to75% protection at 17.5 Gy.Conclusions: This study demonstrates for the first time that significant radioprotection of the salivary glands is possible with Tempol in C3H mice.