# Common molecular profile of multiple structurally distinct warfare arsenicals in causing cutaneous chemical vesicant injury

## TL;DR

This study identifies common molecular pathways triggered by different arsenical chemicals that cause skin damage, similar to those caused by lewisite.

## Contribution

The study reveals a shared molecular profile among structurally distinct arsenicals in causing skin injury, including immune cell infiltration and disrupted cell junctions.

## Key findings

- DPCA and DPCYA caused significant skin erythema, edema, and immune cell infiltration, while DECA did not.
- RT-PCR confirmed increased inflammation, ROS, and UPR signaling in DPCA/DPCYA-exposed skin.
- Disrupted tight and adherens junction proteins were linked to apoptotic cell death in epidermal keratinocytes.

## 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.