Use of the mouse ear vesicant model to evaluate the effectiveness of ebselen as a countermeasure to the nitrogen mustard mechlorethamine. Issue 12 (17th December 2013)

• Record Type: Journal Article
• Authors: Lulla, Anju; Reznik, Sandra; Trombetta, Louis; Billack, Blase
• Is Part Of: Journal of applied toxicology. Volume 34:Issue 12(2014)
• Page Start: 1373
• Page End: 1378
• Publication Date: 2013-12-17
• Subjects: Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.2969
• Languages: English
• ISSNs: 0260-437X

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>Previous studies in this and other laboratories have demonstrated that ebselen (EB‐1), an organoselenium compound, spares cells from mechlorethamine (HN2) toxicity <italic>in vitro</italic>. In the present study, the hypothesis that EB‐1 will reduce dermal toxicity of HN2 <italic>in vivo</italic> 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 <italic>in vivo</italic> model. Copyright © 2013 John Wiley &amp; Sons, Ltd.</p> </abstract>