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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\u00a0h followed by scar formation at 72\u00a0h, 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\u00a0h, however, epidermal cell necrosis was seen at 72\u00a0h. Significantly high number of macrophage infiltration observed at 6\u00a0h, whereas peak neutrophil infiltration occurred at 72\u00a0h. 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\/\u03b1-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.<\/jats:p>","DOI":"10.1038\/s41598-024-83513-1","type":"journal-article","created":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T15:15:36Z","timestamp":1740237336000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Common molecular profile of multiple structurally distinct warfare arsenicals in causing cutaneous chemical vesicant injury"],"prefix":"10.1038","volume":"15","author":[{"given":"Ritesh Kumar","family":"Srivastava","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhail","family":"Muzaffar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasim","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohit","family":"Bansal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupam","family":"Agarwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Athar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,22]]},"reference":[{"key":"83513_CR1","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1111\/j.1745-7254.2008.00771.x","volume":"29","author":"WY Au","year":"2008","unstructured":"Au, W. 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