Blister or
vesicant chemical warfare agents (CWAs) have been widely used in different military conflicts, including World War I and the Iran-Iraq War. However, their mechanism of action is not fully understood.
Sulfur and
nitrogen mustard exert toxic effects not only through the alkylation of
thiol-bearing macromolecules, such as
DNA and
proteins, but also produce
free radicals that can develop direct toxic effects in target organs such as the eyes, skin, and respiratory system. The lack of effective treatments against
vesicant CWAs-induced injury makes us consider, in this complex scenario, the use and development of
melatonin-based therapeutic strategies. This multifunctional indoleamine could facilitate neutralization of the oxidative stress, modulate the inflammatory response, and prevent the DNA damage, as well as the long-term health consequences mediated by
vesicant CWAs-induced epigenetic mechanisms. In this context, it would be essential to develop new galenic formulations for the use of orally and/or topically applied
melatonin for the prophylaxis against
vesicant CWAs, as well as the development of post-exposure treatments in the near future.