Impact of melatonin effects on toxicology of vesicant chemical warfare agents: When science meets reality

In this review we focused our attention on sulfur mustard [bis(2-chloroethyl) sulphide], the main vesicant chemical warfare agent (CWA), which has been widely used in different military conflicts, including World War I and the Iran-Iraq war. Moreover, the evolution of the recent Iraq and Syria conflicts suggests that terrorist groups are aware of the significant psychological and media effects that would be produced by the mere attempt to use CWAs. Sulfur mustard can produce the alkylation of macromolecules bearing sulfhydryl groups, such as DNA and proteins. This vesicant can also generate free radicals which can develop toxicity in the areas exposed, such as the eyes, skin, respiratory tract (inhalation) and gastrointestinal tract (ingestion). In this respect, we advance and propose three salvage mechanisms through which a broad-spectrum multipotent molecule, melatonin, could facilitate neutralization of the toxic damage induced by sulfur mustard radical scavenging. We also speculate that the long-term effects of varying severity can appear after acute poisoning. Besides, melatonin-based therapy strategies can modulate of epigenetic mechanisms and become very suitable for the clinical treatment of victimized patients. However, the utilization of melatonin as a “therapeutic bullet” addressed to counteract the vesicant CWAs needs much additional in vitro research as well as systematic animal studies and controlled translational trials.