Early indicators of survival following exposure to mustard gas: Protective role of 25(OH)D

Lopa M. Das; Amy M. Binko; Zachary P. Traylor; Lori R. Duesler; Scott M. Dynda; Sara Debanne; Kurt Q. Lu

doi:10.1016/j.toxlet.2016.02.013

Early indicators of survival following exposure to mustard gas: Protective role of 25(OH)D

Lopa M. Das, Amy M. Binko, Zachary P. Traylor, Lori R. Duesler, Scott M. Dynda, Sara Debanne, Kurt Q. Lu^*

^*Corresponding author for this work

Dermatology

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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.

Original language	English (US)
Pages (from-to)	9-15
Number of pages	7
Journal	Toxicology Letters
Volume	248
DOIs	https://doi.org/10.1016/j.toxlet.2016.02.013
State	Published - Apr 25 2016

Funding

The authors would like to thank K.D. Cooper and T.S. McCormick for critical discussions and reading of the manuscript; K. Honda, G. Jacobs, L. Sandhaus, M. Cohens, and T. Bonfield for H&E tissue slide analysis; Skin Disease Research Center at Case Western Reserve University. The authors would like to thank Battelle Organization for conducting all experiments with sulfur mustard. This work was supported by the CounterACT Efficacy Research Facility (CERF) through the NIH Office of the Director via an interagency agreement between the NIAID and Department of Defense (DoD) and prepared under the auspices of both the NIH and the DoD Defense Technical Information Center (DTIC) under the Chemical, Biological, Radiological & Nuclear Defense Information Analysis Center (CBRNIAC) program, Contract No. SP0700-00-D-3180, Delivery Order Number 0687, CBRNIAC Task 832/CB-I O-OOI2. This work was funded by National Institute of Health (U01-AR064144), National Institute of Arthritis Musculoskeletal and Skin Diseases (NIAMS) (P30-AR039750).

Keywords

25(OH)D
Inflammation
Intervention
Mortality model
Sulfur mustard

ASJC Scopus subject areas

Toxicology

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10.1016/j.toxlet.2016.02.013

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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.",

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AU - Das, Lopa M.

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AU - Dynda, Scott M.

AU - Debanne, Sara

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AB - 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.

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Early indicators of survival following exposure to mustard gas: Protective role of 25(OH)D

Abstract

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Keywords

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