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

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.

Topical efficacy of dimercapto-chelating agents against lewisite-induced skin lesions in SKH-1 hairless mice.

Lewisite is a potent chemical warfare arsenical vesicant that can cause severe skin lesions. Today, lewisite exposure remains possible during demilitarization of old ammunitions and as a result of deliberate use. Although its cutaneous toxicity is not fully elucidated, a specific antidote exists, the British anti-lewisite (BAL, dimercaprol) but it is not without untoward effects. Analogs of BAL, less toxic, have been developed such as meso-2,3-dimercaptosuccinic acid (DMSA) and have been employed for the treatment of heavy metal poisoning. However, efficacy of DMSA against lewisite-induced skin lesions remains to be determined in comparison with BAL. We have thus evaluated in this study the therapeutic efficacy of BAL and DMSA in two administration modes against skin lesions induced by lewisite vapor on SKH-1 hairless mice. Our data demonstrate a strong protective efficacy of topical application of dimercapto-chelating agents in contrast to a subcutaneous administration 1h after lewisite exposure, with attenuation of wound size, necrosis and impairment of skin barrier function. The histological evaluation also confirms the efficacy of topical application by showing that treatments were effective in reversing lewisite-induced neutrophil infiltration. This protective effect was associated with an epidermal hyperplasia. However, for all the parameters studied, BAL was more effective than DMSA in reducing lewisite-induced skin injury. Together, these findings support the use of a topical form of dimercaprol-chelating agent against lewisite-induced skin lesion within the first hour after exposure to increase the therapeutic management and that BAL, despite its side-effects, should not be abandoned.

Sulfur mustard cutaneous injury characterization based on SKH-1 mouse model: relevance of non-invasive methods in terms of wound healing process analyses.

BACKGROUND: To date, sulphur mustard (SM) cutaneous toxicity has been commonly assessed on account of several animal models such as pigs and weanling pigs. Few experiments however, have been carried out on mice so far. In this study, we aimed at quantifying spontaneous wound healing processes after SM exposure on a SKH-1 mouse model through non-invasive methods over an extended period of time. METHODS: Animals were exposed to 10 µL net SM in a vapor cup system. Measurements of barrier function (Transepidermal water loss), elasticity, skin color exposed to SM vapors were determined by evaporimetry, cutometer and image analysis on 23 animals up to 28 days. Results were subsequently correlated with histological and biochemical analyses. RESULTS: The TEWL parameter stands as a top-ranking criterion to keep track of skin barrier restoration after SM cutaneous intoxication in our SKH-1 mouse model. The R2 and R6 elasticity parameters or L° for the skin color exhibited their ability to be restored after 28 days of SM exposure. CONCLUSION: Our findings suggest that bio-engineering methods are eligible to evaluate new treatments on SM-induced skin SKH-1 mouse lesions, thus making an allowance for less invasive methods such as histological, genomic or proteomic approaches.