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Skin Models Used to Define Mechanisms of Action of Sulfur Mustard

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Publisher

CAMBRIDGE UNIV PRESS
DOI: 10.1017/dmp.2023.177

Keywords

animal models; dermatotoxicity; sulfur mustard; wound healing

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Sulfur mustard is harmful to human skin, and animal models are crucial for studying its effects and assessing the efficacy of therapeutic drugs. Hairless guinea pigs and swine are ideal models with similar skin morphology to humans, while mice, rats, and rabbits have limitations.
Sulfur mustard (SM) is a threat to both civilian and military populations. Human skin is highly sensitive to SM, causing delayed erythema, edema, and inflammatory cell infiltration, followed by the appearance of large fluid-filled blisters. Skin wound repair is prolonged following blistering, which can result in impaired barrier function. Key to understanding the action of SM in the skin is the development of animal models that have a pathophysiology comparable to humans such that quantitative assessments of therapeutic drugs efficacy can be assessed. Two animal models, hairless guinea pigs and swine, are preferred to evaluate dermal products because their skin is morphologically similar to human skin. In these animal models, SM induces degradation of epidermal and dermal tissues but does not induce overt blistering, only microblistering. Mechanisms of wound healing are distinct in these animal models. Whereas a guinea pig heals by contraction, swine skin, like humans, heals by re-epithelialization. Mice, rats, and rabbits are also used for SM mechanistic studies. However, healing is also mediated by contraction; moreover, only microblistering is observed. Improvements in animal models are essential for the development of therapeutics to mitigate toxicity resulting from dermal exposure to SM.

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