Common molecular profile of multiple structurally distinct warfare arsenicals in causing cutaneous chemical vesicant injury
Abstract Skin exposure to arsenicals such as lewisite and phenylarsine oxide leads to severe cutaneous damage. Here, we characterized the molecular pathogenesis of skin injury caused by additionally structurally distinct warfare arsenicals including diphenylchlorarsine (DPCA), diphenylcyanoarsine (D...
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Nature Portfolio
2025-02-01
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| author | Ritesh Kumar Srivastava Suhail Muzaffar Jasim Khan Mohit Bansal Anupam Agarwal Mohammad Athar |
| author_facet | Ritesh Kumar Srivastava Suhail Muzaffar Jasim Khan Mohit Bansal Anupam Agarwal Mohammad Athar |
| author_sort | Ritesh Kumar Srivastava |
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| description | Abstract Skin exposure to arsenicals such as lewisite and phenylarsine oxide leads to severe cutaneous damage. Here, we characterized the molecular pathogenesis of skin injury caused by additionally structurally distinct warfare arsenicals including diphenylchlorarsine (DPCA), diphenylcyanoarsine (DPCYA), diethylchloroarsine (DECA). Cutaneous exposure to DPCA/DPCYA showed marked increase in skin erythema and edema at 6 and 24 h followed by scar formation at 72 h, while DECA did not produce such visual injuries in mouse skin. Clinical observations showed significant increase in Draize score and skin bi-fold thickness in a time-dependent manner. DPCA or DPCYA-exposed skin histology revealed highly inflamed hypodermal areas with infiltrated immune cells at 6 and 24 h, however, epidermal cell necrosis was seen at 72 h. Significantly high number of macrophage infiltration observed at 6 h, whereas peak neutrophil infiltration occurred at 72 h. Number of micro-blisters also increased. However, these effects were nonsignificant following topical DECA exposure. RT-PCR confirmed augmented inflammatory responses in the skin challenged with both DPCA/DPCYA, which accompanied increased ROS and unfolded protein response (UPR) signaling. DECA also increased ROS with changes in UPR. Disrupted tight (Yap/ZO-1) and adherens (Yap/α-Catenin) junction proteins underlie time-dependent apoptotic cell death of epidermal keratinocytes. Thus, these studies identify arsenicals-manifested signaling pathways similar to those of lewisite. |
| format | Article |
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| spelling | doaj-art-a770ab52cdf74a39a2e2b0cc6dc3fa232025-08-20T02:15:00ZengNature PortfolioScientific Reports2045-23222025-02-0115111710.1038/s41598-024-83513-1Common molecular profile of multiple structurally distinct warfare arsenicals in causing cutaneous chemical vesicant injuryRitesh Kumar Srivastava0Suhail Muzaffar1Jasim Khan2Mohit Bansal3Anupam Agarwal4Mohammad Athar5UAB Research Center of Excellence in Arsenicals, Department of Dermatology, University of Alabama at BirminghamUAB Research Center of Excellence in Arsenicals, Department of Dermatology, University of Alabama at BirminghamUAB Research Center of Excellence in Arsenicals, Department of Dermatology, University of Alabama at BirminghamDepartment of Pathology, University of Alabama at BirminghamDivision of Nephrology, Department of Medicine, University of Alabama at BirminghamUAB Research Center of Excellence in Arsenicals, Department of Dermatology, University of Alabama at BirminghamAbstract Skin exposure to arsenicals such as lewisite and phenylarsine oxide leads to severe cutaneous damage. Here, we characterized the molecular pathogenesis of skin injury caused by additionally structurally distinct warfare arsenicals including diphenylchlorarsine (DPCA), diphenylcyanoarsine (DPCYA), diethylchloroarsine (DECA). Cutaneous exposure to DPCA/DPCYA showed marked increase in skin erythema and edema at 6 and 24 h followed by scar formation at 72 h, while DECA did not produce such visual injuries in mouse skin. Clinical observations showed significant increase in Draize score and skin bi-fold thickness in a time-dependent manner. DPCA or DPCYA-exposed skin histology revealed highly inflamed hypodermal areas with infiltrated immune cells at 6 and 24 h, however, epidermal cell necrosis was seen at 72 h. Significantly high number of macrophage infiltration observed at 6 h, whereas peak neutrophil infiltration occurred at 72 h. Number of micro-blisters also increased. However, these effects were nonsignificant following topical DECA exposure. RT-PCR confirmed augmented inflammatory responses in the skin challenged with both DPCA/DPCYA, which accompanied increased ROS and unfolded protein response (UPR) signaling. DECA also increased ROS with changes in UPR. Disrupted tight (Yap/ZO-1) and adherens (Yap/α-Catenin) junction proteins underlie time-dependent apoptotic cell death of epidermal keratinocytes. Thus, these studies identify arsenicals-manifested signaling pathways similar to those of lewisite.https://doi.org/10.1038/s41598-024-83513-1Chemical warfare agentsArsenicalsSkin injury |
| spellingShingle | Ritesh Kumar Srivastava Suhail Muzaffar Jasim Khan Mohit Bansal Anupam Agarwal Mohammad Athar Common molecular profile of multiple structurally distinct warfare arsenicals in causing cutaneous chemical vesicant injury Scientific Reports Chemical warfare agents Arsenicals Skin injury |
| title | Common molecular profile of multiple structurally distinct warfare arsenicals in causing cutaneous chemical vesicant injury |
| title_full | Common molecular profile of multiple structurally distinct warfare arsenicals in causing cutaneous chemical vesicant injury |
| title_fullStr | Common molecular profile of multiple structurally distinct warfare arsenicals in causing cutaneous chemical vesicant injury |
| title_full_unstemmed | Common molecular profile of multiple structurally distinct warfare arsenicals in causing cutaneous chemical vesicant injury |
| title_short | Common molecular profile of multiple structurally distinct warfare arsenicals in causing cutaneous chemical vesicant injury |
| title_sort | common molecular profile of multiple structurally distinct warfare arsenicals in causing cutaneous chemical vesicant injury |
| topic | Chemical warfare agents Arsenicals Skin injury |
| url | https://doi.org/10.1038/s41598-024-83513-1 |
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