Kinetics of tempol for prevention of xerostomia following head and neck irradiation in a mouse model
Kinetics of tempol for prevention of xerostomia following head and neck irradiation in a mouse model
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DOI：
10.1158/1078-0432.ccr-05-0958
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发表时间：
2005-10-15
影响因子：
11.5
通讯作者：
Baum, BJ
中科院分区：
文献类型：
--
作者：
Cotrim, AP;Sowers, AL;Baum, BJ
目的：放射治疗是治疗头颈部癌症的常用方法。辐射场中的唾液腺会受到这个过程的严重影响。本研究的目的是研究稳定的氮氧自由基4-羟基-2，2，6，6-四甲基哌啶-N-氧基（tempol）的药代动力学特征，相对于放射防护的唾液腺。实验设计：为了评估不同剂量和给药时间的效果，C3 H小鼠的头部暴露于15戈伊的单次照射剂量，与i. p. tempol注射。为了分析其他给药途径，我们通过肌内注射275 mg/kg tempol，静脉注射，或s.c.照射前10分钟。我们还测试了以局部形式（漱口水或凝胶）口服给予tempol是否提供任何唾液腺保护。照射前10分钟）显著降低了照射诱导的唾液功能减退（类似于50-60%）。l.v.或s.c.给予Tempol也显示出显著的辐射防护，而i.m.事实证明，管理是无效的。局部使用的tempol，无论是漱口水或凝胶，也是radioprotectic.Conclusions：我们的研究结果强烈表明，tempol是一个很有前途的候选人，为临床应用，以保护唾液腺接受放射治疗的头颈部癌症患者。
Purpose: Radiotherapy is commonly used to treat the majority of patients with head and neck cancers. Salivary glands in the radiation field are dramatically affected by this procedure. The purpose of this study was to examine pharmacokinetic characteristics of the stable nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) with respect to radioprotection of the salivary glands.Experimental Design: To evaluate the effect of different doses and times of administration, the heads of C3H mice were exposed to a single irradiation dose of 15 Gy, with i.p. tempol injection. To analyze other routes of administration, we injected 275 mg/kg tempol by an i.m., i.v., or s.c. route, 10 minutes before irradiation. We also tested whether oral administration of tempol in a topical form (either in a mouthwash or gel) provided any salivary gland protection.Results: Tempol treatment (137.5 or 275 mg/kg, i.p., 10 minutes before irradiation) significantly reduced irradiation-induced salivary hypofunction (similar to 50-60%). l.v. or s.c. administration of tempol also showed significant radioprotection, whereas i.m. administration proved to be ineffective. Topical use of tempol, either as a mouthwash or gel, also was radioprotective.Conclusions: Our results strongly suggest that tempol is a promising candidate for clinical application to protect salivary glands in patients undergoing radiotherapy for head and neck cancers.