title: Use of the mouse ear vesicant model to evaluate the effectiveness of ebselen as a countermeasure to the nitrogen mustard mechlorethamine.
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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY, 11439, USA.
authors.forename: Anju
authors.initials: A
authors.lastname: Lulla
authors.forename: Sandra
authors.initials: S
authors.lastname: Reznik
authors.forename: Louis
authors.initials: L
authors.lastname: Trombetta
authors.forename: Blase
authors.initials: B
authors.lastname: Billack
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001393:Azoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004423:Ear; D004487:Edema / Q000473:pathology / Q000517:prevention & control; D007509:Irritants / Q000633:toxicity*; D054833:Isoindoles; D008297:Male; D008466:Mechlorethamine / Q000633:toxicity*; D051379:Mice; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D023422:Skin Irritancy Tests
chemical_list: D001393:Azoles; D007509:Irritants; D054833:Isoindoles; D016566:Organoselenium Compounds; D020011:Protective Agents; C042986:ebselen; D008466:Mechlorethamine
keywords: countermeasure; ebselen; mechlorethamine; mouse ear; nitrogen mustard; organoselenium