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      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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          Abstract

          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 24 h after treatment; whereas tissue injury consistent with vesication was observed at the higher test doses of HN2 (≥ 0.250 µmol 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 15 min, 4 and 8 h after HN2 exposure. Using this approach, both HC and EB-1 were found to reduce tissue swelling associated with HN2 toxicity 24 h 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.

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          Author and article information

          Journal
          J Appl Toxicol
          Journal of applied toxicology : JAT
          Wiley
          1099-1263
          0260-437X
          Dec 2014
          : 34
          : 12
          Affiliations
          [1 ] Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY, 11439, USA.
          Article
          10.1002/jat.2969
          24347431
          09937863-f8dc-46da-a593-ed96ca8a8000
          History

          ebselen,mouse ear,nitrogen mustard,mechlorethamine,organoselenium,countermeasure

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