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

Sulfur and nitrogen mustards, bis(2-chloroethyl)sulfide and tertiary bis(2-chloroethyl) amines, respectively, are vesicant warfare agents with alkylating activity. Moreover, oxidative/nitrosative stress, inflammatory response induction, metalloproteinases activation, DNA damage or calcium disruption are some of the toxicological mechanisms of sulfur and nitrogen mustard-induced injury that affects the cell integrity and function. In this review, we not only propose melatonin as a therapeutic option in order to counteract and modulate several pathways involved in physiopathological mechanisms activated after exposure to mustards, but also for the first time, we predict whether metabolites of melatonin, cyclic-3-hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykynuramine, and N1-acetyl-5-methoxykynuramine could be capable of exerting a scavenger action and neutralize the toxic damage induced by these blister agents.

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

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.

Toxicity induced by chemical warfare agents: insights on the protective role of melatonin.

Chemical Warfare Agents (CWAs) are substances that can be used to kill, injure or incapacitate an enemy in warfare, but also against civilian population in terrorist attacks. Many chemical agents are able to generate free radicals and derived reactants, excitotoxicity process, or inflammation, and as consequence they can cause neurological symptoms and damage in different organs. Nowadays, taking into account that total immediate decontamination after exposure is difficult to achieve and there are not completely effective antidotes and treatments against all CWAs, we advance and propose that medical countermeasures against CWAs poisoning would benefit from a broad-spectrum multipotent molecule.

[Neurotoxins with anticholinesterase activity and their possible use as warfare agents].

Anatoxin-a(s), onchidal and fasciculins are neurotoxins with anticholinesterase activity. An intoxication by these neurotoxins is characterized by cholinergic syndromes similar to organophosphate insecticide and nerve agent intoxications. Anticholinesterase neurotoxins, as well as other toxins, have some disadvantages if used as weapons of mass destruction.