Use of the mouse ear vesicant model to evaluate the effectiveness of ebselen as a countermeasure to the nitrogen mustard mechlorethamine
Use of the mouse ear vesicant model to evaluate the effectiveness of ebselen as a countermeasure to the nitrogen mustard mechlorethamine
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DOI：
10.1002/jat.2969
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发表时间：
2014-12-01
影响因子：
3.3
通讯作者：
Billack, Blase
中科院分区：
文献类型：
--
作者：
Lulla, Anju;Reznik, Sandra;Billack, Blase
该实验室和其他实验室之前的研究表明，依布硒啉 (EB-1)（一种有机硒化合物）在体外可以使细胞免受氮芥 (HN2) 毒性。在本研究中，提出了EB-1会降低HN2体内皮肤毒性的假设，并发现该假设是有价值的。使用小鼠耳部出疱模型 (MEVM)，局部应用 HN2，在治疗 24 小时后对耳部肿胀和厚度显示出剂量依赖性效应；而在较高的 HN2 测试剂量（每耳 0.250 μmol）下观察到与起泡一致的组织损伤。为了使用 MEVM 检查 HN2 对策活性，在 HN2 暴露后 15 分钟、4 小时和 8 小时，将氢化可的松 (HC)（作为阳性对照）或 EB-1（测试对策）作为三种局部治疗进行给药。使用这种方法，发现 HC 和 EB-1 在暴露于起泡剂 24 小时后可减少与 HN2 毒性相关的组织肿胀。总而言之，这些数据首次证明了 EB-1 在相关体内模型中作为发泡对策的有效性。版权所有 (c) 2013 John Wiley & Sons, Ltd。本研究的目的是首次在体内模型中证明依布硒啉 (EB-1) 作为发泡对策的有效性。使用小鼠耳起泡模型 (MEVM)，局部应用 HN2 显示出剂量依赖性损伤。为了检查 HN2 对抗活性，在 HN2 暴露后使用氢化可的松 (HC) 或 EB-1 作为三种局部治疗。 HC 和 EB-1 均被发现可减少暴露于发泡剂 24 小时后与 HN2 毒性相关的组织肿胀。
Previous studies in this and other laboratories have demonstrated that ebselen (EB-1), an organoselenium compound, spares cells from mechlorethamine (HN2) toxicity in vitro. In the present study, the hypothesis that EB-1 will reduce dermal toxicity of HN2 in vivo is put forward and found to have merit. Using the mouse ear vesicant model (MEVM), HN2, applied topically, showed a dose-dependent effect upon ear swelling and thickness 24h after treatment; whereas tissue injury consistent with vesication was observed at the higher test doses of HN2 ( 0.250 mu mol per ear). To examine HN2 countermeasure activity using the MEVM, either hydrocortisone (HC), as a positive control, or EB-1, the test countermeasure, was administered as three topical treatments 15min, 4 and 8h after HN2 exposure. Using this approach, both HC and EB-1 were found to reduce tissue swelling associated with HN2 toxicity 24h after exposure to the vesicant. Taken together, these data demonstrate for the first time the effectiveness of EB-1 as a vesicant countermeasure in a relevant in vivo model. Copyright (c) 2013 John Wiley & Sons, Ltd.The goal of the present study was to demonstrate for the first time the effectiveness of ebselen (EB-1) as a vesicant countermeasure in an in vivo model. Using the mouse ear vesicant model (MEVM), HN2, applied topically, showed a dose-dependent injury. To examine HN2 countermeasure activity, either hydrocortisone (HC) or EB-1 was administered as three topical treatments after HN2 exposure. Both HC and EB-1 were found to reduce tissue swelling associated with HN2 toxicity 24 h after vesicant exposure.