Sulfur mustard-induced skin burns in weanling swine evaluated clinically and histopathologically†

Reid, Frances M.; Graham, John S.; Niemuth, Nancy A.; Singer, Allen W; Janny, Stephen J.; Johnson, John

doi:10.1002/1099-1263(200012)20:1+<::aid-jat673>3.0.co;2-o

Cited by 22 publications

(16 citation statements)

References 26 publications

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“…The weanling pig is another model used for wound healing studies because of its similarity with human skin. This model shows microblister formation and necrosis following exposure to HD at higher doses (King and Monteiro-Riviere, 1990; Reid et al, 2000). From an experimental standpoint it is important to mention that most of the skin vesicant and toxicity models developed utilizing exposure to HD require special containment facilities and involve multiple procedural limitations.…”

Section: Discussionmentioning

confidence: 94%

2-Chloroethyl ethyl sulfide causes microvesication and inflammation-related histopathological changes in male hairless mouse skin

et al. 2011

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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 epidermaldermal 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.

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Section: Discussionmentioning

confidence: 94%

2-Chloroethyl ethyl sulfide causes microvesication and inflammation-related histopathological changes in male hairless mouse skin

et al. 2011

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“…Most studies on the mechanism of action of sulfur mustard have used animal models including mice, guinea pigs, pigs and rabbits (Dannenberg et al , 1985; Harada et al , 1987; Monteiro-Riviere and Inman, 1997; Monteiro-Riviere et al , 1999; Babin et al , 2000; Reid et al , 2000; Dachir et al , 2002; Dachir et al , 2004; Wormser et al , 2004a; Pal et al , 2009; Tewari-Singh et al , 2009; Dachir et al , 2010). While these models recapitulate many of the actions of sulfur mustard in human skin including inflammation, necrosis and wound repair, gross blistering, a major response following human exposure is not observed (Smith et al , 1997a).…”

Section: Introductionmentioning

confidence: 99%

Expression of proliferative and inflammatory markers in a full-thickness human skin equivalent following exposure to the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide

Black

Hayden

Casillas

et al. 2010

Toxicology and Applied Pharmacology

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Sulfur mustard is a potent vesicant that induces inflammation, edema and blistering following dermal exposure. To assess molecular mechanisms mediating these responses, we analyzed the effects of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide, on EpiDerm-FT™, a commercially available full-thickness human skin equivalent. CEES (100–1000 μM) caused a concentration-dependent increase in pyknotic nuclei and vacuolization in basal keratinocytes; at high concentrations (300–1000 μM), CEES also disrupted keratin filament architecture in the stratum corneum. This was associated with time-dependent increases in expression of proliferating cell nuclear antigen, a marker of cell proliferation, and poly(ADP-ribose) polymerase (PARP) and phosphorylated histone H2AX, markers of DNA damage. Concentration- and time-dependent increases in mRNA and protein expression of eicosanoid biosynthetic enzymes including COX-2, 5-lipoxygenase, microsomal PGE2 synthases, leukotriene (LT) A4 hydrolase and LTC4 synthase were observed in CEES-treated skin equivalents, as well as in antioxidant enzymes, glutathione S-transferases A1–2 (GSTA1–2), GSTA3 and GSTA4. These data demonstrate that CEES induces rapid cellular damage, cytotoxicity and inflammation in full-thickness skin equivalents. These effects are similar to human responses to vesicants in vivo and suggest that the full thickness skin equivalent is a useful in vitro model to characterize the biological effects of mustards and to develop potential therapeutics.

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“…The eschar sloughs in a 4-to 6-day time period, finally leaving a pigmented scar (Reid et al, 2000(Reid et al, , 2007. A burn caused by a blister agent is much slower to heal than a thermal burn, likely because of the multiple mechanisms by which the agent affects biological tissue, as discovered during World War I and reestablished in Iranian casualties from the Iran-Iraq war (1980)(1981)(1982)(1983)(1984)(1985)(1986)(1987)(1988).…”

Section: Background: Vesicating Agents (Distilled Sulfur Mustard Hd;mentioning

confidence: 99%

Rapid Decontamination of Chemical Warfare Agents from the Skin

Clarkson¹,

Gordon

2015

Handbook of Toxicology of Chemical Warfare Agents

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Sulfur mustard-induced skin burns in weanling swine evaluated clinically and histopathologically†

Cited by 22 publications

References 26 publications

2-Chloroethyl ethyl sulfide causes microvesication and inflammation-related histopathological changes in male hairless mouse skin

2-Chloroethyl ethyl sulfide causes microvesication and inflammation-related histopathological changes in male hairless mouse skin

Expression of proliferative and inflammatory markers in a full-thickness human skin equivalent following exposure to the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide

Rapid Decontamination of Chemical Warfare Agents from the Skin

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