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

Abstract

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.

In Vivo Assessment of Skin Chemical Burns in Exposure to Vesicants and the Efficacy of an Antidote Formula in Different Pharmaceutical Forms. An Experimental Approach

“…To optimize effective therapeutic solutions, studies were performed using the chemical vesicant 2-chloroethyl-ethyl sulphide (CEES). It has a chemical structure similar to that of the class of sulphur-based vesicant chemicals and acts through similar pathogenic mechanisms of acute exposure (induction of oxidative stress and inflammatory response), but is less toxic, being a valid experimental alternative for detoxification and antidote studies [31]. Skin lesions caused by vesicant chemicals are characterized by oedema, inflammation, and cell death, mainly of the basal layer of keratinocytes, with varying immunological and pathological changes in the acute phase.…”

Melatonin - A Cutaneous Perspective

“…Reiter et al proposed that melatonin may be given consideration for prophylactic use or treatment alone or in combination with other drugs to combat Covid-19 owing to its multiple actions as an anti-inflammatory, anti-oxidant, and anti-viral (against other viruses) agent. 66 Melatonin, like other immunomodulatory agents, may be used as an effective adjuvant besides vaccination to boost the vaccine's effectiveness in patients with both compromised and healthy systemic and cutaneous immune systems. 67,68…”

Role of hair follicles in the pathogenesis of arsenical‐induced cutaneous damage

“…In addition to the use of these chemicals by states, some terrorist organizations may also have access to chemical, biological, and radiological agents for their potential use as weapons of great lethality 14 . We have been interested in investigating the pathogenesis induced by potent skin irritant chemicals that cause blistering following their percutaneous exposure 15 . This class of chemicals is known as vesicants.…”

“…14 We have been interested in investigating the pathogenesis induced by potent skin irritant chemicals that cause blistering following their percutaneous exposure. 15 This class of chemicals is known as vesicants.…”