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

Abstract

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.

Melatonin as Modulator for Sulfur and Nitrogen Mustard-Induced Inflammation, Oxidative Stress and DNA Damage: Molecular Therapeutics

“…The melatonin cascade also enables extremely efficient electron transfer [80] to scavenge most RONS [25,53,81,82] and the ONOO - [83,84]. In addition, genomic regulation exerted by melatonin modulates pro-oxidant and antioxidant mechanisms and mitochondrial metabolism [85,86], therefore enhancing cellular responses against DNA alteration and chemical damage [51,[87][88][89]. This multidimensional response of melatonin towards the repair of modified sites, the elimination of macromolecule damaging agents and the activation of antioxidative defense gives it proficiency to neutralize mustard pathology.…”

Toxicology of Blister Agents: Is Melatonin a Potential Therapeutic Option?

“…(iv) Bacterial skin infections by mustard exposure may be prevented by the antimicrobial effect of melatonin [ 35 ]. Therefore, after mustard exposure, the melatonin supplementation may not only reduce the oxidative damage and alkylation of cellular macromolecules [ 36 ] but also improve the cutaneous regenerative potential [ 37 ].…”

“…Previously, our research group reported through computational calculations the hydrogen-atom transfer (HAT) as the suitable mechanism to quench SM, furnishing the much less toxic thiirane [ 36 , 101 ]. The recognized free radical scavenging capacity of melatonin also facilitates the neutralization of mechlorethamine-induced toxic damage.…”