Time course of lewisite‐induced skin lesions and inflammatory response in the SKH‐1 hairless mouse model

Abstract

Data on the toxicity of lewisite (L), a vesicant chemical warfare agent, are scarce and conflicting, and the use of the specific antidote is not without drawbacks. This study was designed to evaluate if the SKH-1 hairless mouse model was suitable to study the L-induced skin injuries. We studied the progression of lesions following exposure to L vapors for 21 days using paraclinical parameters (color, transepidermal water loss (TEWL), and biomechanical measurements), histological assessments, and biochemical indexes of inflammation. Some data were also obtained over 27 weeks. The development of lesions was similar to that reported in other models. The TEWL parameter appeared to be the most appropriate index to follow their progression. Histological analysis showed inflammatory cell infiltration and microvesications at day 1 and a complete wound closure by day 21. Biochemical studies indicated a deregulation of the levels of several cytokines and receptors involved in inflammation. An increase in the quantity of pro-matrix metalloproteinases 2 and 9 was shown as observed in other models. This suggests that the SKH-1 mouse model is relevant for the investigation of the physiopathological process of skin lesions induced by L and to screen new treatment candidates.

Biological and environmental hazards associated with exposure to chemical warfare agents: arsenicals

“…Histological analysis showed inflammatory cell infiltration and microvesication, which is initiated at day 1 and requires at least 21 days for complete wound closure. The temporal molecular changes, including dysregulation of expression of cytokines and their receptors involved in the manifestations of inflammation and increase in pro‐matrix metalloproteinases 2/9, were more or less similar to those observed in other models . Animal studies did not demonstrate teratogenicity or reproductive effects of Lewisite, at least at the doses tested …”

“…Wound healing is accompanied by skin regeneration at the edges of the wound. These macroscopic changes are accompanied by temporal pathological observations, such as microvesication, degeneration of the basal cells in the epidermis, infiltration of inflammatory cells, and cell death, in both the epidermis and dermis . Generally, the pattern of skin lesion development following Lewisite exposure is similar to that found following mustard agent challenge.…”

“…17 Animal models, including horse, swine, hairless guinea pig, and mice, have been used to investigate the pathogenesis of skin lesions. 4,13,19,20 Changes in the skin following Lewisite exposure in the majority of these models are generally similar and have been characterized by the early onset of erythema followed by edema of the skin, which gradually develops a grayish and brownish color that clearly demarcates the involved and normal skin margins. Wound healing is accompanied by skin regeneration at the edges of the wound.…”

Time course of skin features and inflammatory biomarkers after liquid sulfur mustard exposure in SKH-1 hairless mice

“…The skin of hairless SKH-1 control mice is characterized by a thin stratified epidermis above a dermis containing numerous sebaceous glands and dermal cysts remnant of hair follicles (Clery- Nguon et al, 2014). Skin structure was unaffected after topical application of dichloromethane (data not shown).…”

Clinical progression of ocular injury following arsenical vesicant lewisite exposure

“…LEW was developed as an arsenical vesicant during World War I but was not used; however, stockpiles are known to exist posing a potential threat of its accidental exposure or use as a warfare/terrorist agent (5, 6). For example, the former Soviet Union stockpiled LEW as a weaponized mixture alongside the chemical warfare agent sulfur mustard [bis(2-chloroethyl) sulfide), SM] (7).…”