title: 2-Chloroethyl ethyl sulfide causes microvesication and inflammation-related histopathological changes in male hairless mouse skin.
abstract: Sulfur mustard (HD) is a vesicating agent that has been used as a chemical warfare agent in a number of conflicts, posing a major threat in both military conflict and chemical terrorism situations. Currently, we lack effective therapies to rescue skin injuries by HD, in part, due to the lack of appropriate animal models, which are required for conducting laboratory studies to evaluate the therapeutic efficacy of promising agents that could potentially be translated in to real HD-caused skin injury. To address this challenge, the present study was designed to assess whether microvesication could be achieved in mouse skin by an HD analog 2-chloroethyl ethyl sulfide (CEES) exposure; notably, microvesication is a key component of HD skin injury in humans. We found that skin exposure of male SKH-1 hairless mice to CEES caused epidermal-dermal separation indicating microvesication. In other studies, CEES exposure also caused an increase in skin bi-fold thickness, wet/dry weight ratio, epidermal thickness, apoptotic cell death, cell proliferation, and infiltration of macrophages, mast cells and neutrophils in male SKH-1 hairless mouse skin. Taken together, these results establish CEES-induced microvesication and inflammation-related histopathological changes in mouse skin, providing a potentially relevant laboratory model for developing effective countermeasures against HD skin injury in humans.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, 12700 East 19th Avenue, Box C238 P-15 Research 2, Aurora, CO 80045, USA. Anil.Jain@ucdenver.edu
authors.forename: Anil K
authors.initials: AK
authors.lastname: Jain
authors.forename: Neera
authors.initials: N
authors.lastname: Tewari-Singh
authors.forename: David J
authors.initials: DJ
authors.lastname: Orlicky
authors.forename: Carl W
authors.initials: CW
authors.lastname: White
authors.forename: Rajesh
authors.initials: R
authors.lastname: Agarwal
mesh_terms: D000818:Animals; D001768:Blister / Q000139:chemically induced / Q000473:pathology*; D002619:Chemical Warfare Agents / Q000633:toxicity*; D003877:Dermatitis, Contact / Q000209:etiology / Q000473:pathology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008812:Mice, Hairless; D009151:Mustard Gas / Q000031:analogs & derivatives* / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000293:injuries / Q000473:pathology
chemical_list: D002619:Chemical Warfare Agents; C031278:2-chloroethyl ethyl sulfide; D009195:Peroxidase; D009151:Mustard Gas