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Review
. 2016 Jun;1374(1):184-92.
doi: 10.1111/nyas.13099. Epub 2016 Jun 21.

Mustard vesicating agent-induced toxicity in the skin tissue and silibinin as a potential countermeasure

Neera Tewari-Singh  1 , Rajesh Agarwal  1
Affiliations
Review

Mustard vesicating agent-induced toxicity in the skin tissue and silibinin as a potential countermeasure

Neera Tewari-Singh et al. Ann N Y Acad Sci. 2016 Jun.

Abstract

Exposure to the vesicating agents sulfur mustard (SM) and nitrogen mustard (NM) causes severe skin injury with delayed blistering. Depending upon the dose and time of their exposure, edema and erythema develop into blisters, ulceration, necrosis, desquamation, and pigmentation changes, which persist weeks and even years after exposure. Research advances have generated data that have started to explain the probable mechanism of action of vesicant-induced skin toxicity; however, despite these advances, effective and targeted therapies are still deficient. This review highlights studies on two SM analogs, 2-chloroethyl ethyl sulfide (CEES) and NM, and CEES- and NM-induced skin injury mouse models that have substantially added to the knowledge on the complex pathways involved in mustard vesicating agent-induced skin injury. Furthermore, employing these mouse models, studies under the National Institutes of Health Countermeasures Against Chemical Threats program have identified the flavanone silibinin as a novel therapeutic intervention with the potential to be developed as an effective countermeasure against skin injury following exposure to mustard vesicating agents.

Keywords: nitrogen mustard; silibinin; skin injury; sulfur mustard.

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Conflict of interest statement

Conflicts of interest

The authors report no conflicts of interest.

Figures

Figure 1
Figure 1
Mustard vesicating agents (A) chloroethyl ethyl sulfide (CEES, (B) bis(2-chloroethyl) methylamine or nitrogen mustard (NH2, (NM)), and (C) bis(2-chloroethyl) sulfide (sulfur mustard, (SM)
Figure 2
Figure 2
Schematic of important proposed pathways of mustard vesicating agent–induced skin injury based on CEES- and NM-induced in vitro and SKH-1 hairless mouse skin injury models.
Figure 3
Figure 3
Chemical structure of the flavanone silibinin.
See this image and copyright information in PMC

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