title: Early indicators of survival following exposure to mustard gas: Protective role of 25(OH)D.
abstract: The use of sulfur mustard (SM) as a chemical weapon for warfare has once again assumed center stage, endangering civilian and the military safety. SM causes rapid local skin vesication and late-onset systemic toxicity. Most studies on SM rely on obtaining tissue and blood for characterizing burn pathogenesis and assessment of systemic pathology, respectively. However the present study focuses on developing a non-invasive method to predict mortality from high dose skin SM exposure. We demonstrate that exposure to SM leads to a dose dependent increase in wound area size on the dorsal surface of mice that is accompanied by a progressive loss in body weight loss, blood cytopenia, bone marrow destruction, and death. Thus our model utilizes local skin destruction and systemic outcome measures as variables to predict mortality in a novel skin-based model of tissue injury. Based on our recent work using vitamin D (25(OH)D) as an intervention to treat toxicity from SM-related compounds, we explored the use of 25(OH)D in mitigating the toxic effects of SM. Here we show that 25(OH)D offers protection against SM and is the first known demonstration of an intervention that prevents SM-induced mortality. Furthermore, 25(OH)D represents a safe, novel, and readily translatable potential countermeasure following mass toxic exposure.
authors.affiliation: Department of Dermatology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, United States.
authors.forename: Lopa M
authors.initials: LM
authors.lastname: Das
authors.affiliation: Department of Dermatology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, United States.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Binko
authors.affiliation: Department of Dermatology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, United States.
authors.forename: Zachary P
authors.initials: ZP
authors.lastname: Traylor
authors.affiliation: Department of Dermatology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, United States.
authors.forename: Lori R
authors.initials: LR
authors.lastname: Duesler
authors.affiliation: Department of Dermatology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, United States.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Dynda
authors.affiliation: Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, United States.
authors.forename: Sara
authors.initials: S
authors.lastname: Debanne
authors.affiliation: Department of Dermatology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, United States. Electronic address: Kurt.Lu@case.edu.
authors.forename: Kurt Q
authors.initials: KQ
authors.lastname: Lu
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001772:Blood Cell Count; D002112:Calcifediol / Q000008:administration & dosage / Q000627:therapeutic use*; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007274:Injections, Intraperitoneal; D053208:Kaplan-Meier Estimate; D008810:Mice, Inbred C57BL; D009151:Mustard Gas / Q000633:toxicity*; D012871:Skin Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016019:Survival Analysis; D014945:Wound Healing / Q000187:drug effects
chemical_list: D002619:Chemical Warfare Agents; D002112:Calcifediol; D009151:Mustard Gas
keywords: 25(OH)D; Inflammation; Intervention; Mortality model; Sulfur mustard