Romero Alejandro, Ramos Eva, López-Muñoz Francisco, De Los Ríos Cristóbal, Egea Javier, Gil-Martín Emilio, Pita René, Torrado Juan J, Serrano Dolores R, Juberias Antonio
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040 Madrid, Spain.
Faculty of Health Sciences, University Camilo José Cela, C/Castillo de Alarcón 49, Villanueva de la Cañada, 28692 Madrid, Spain.
Diseases. 2021 Apr 10;9(2):27. doi: 10.3390/diseases9020027.
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.
水泡性或糜烂性化学战剂（CWAs）已在包括第一次世界大战和两伊战争在内的不同军事冲突中被广泛使用。然而，它们的作用机制尚未完全明确。硫芥气和氮芥气不仅通过与含硫醇的大分子（如DNA和蛋白质）发生烷基化作用产生毒性效应，还会产生自由基，这些自由基可在眼睛、皮肤和呼吸系统等靶器官中产生直接毒性作用。针对糜烂性化学战剂所致损伤缺乏有效的治疗方法，这促使我们在这种复杂情况下考虑使用和开发基于褪黑素的治疗策略。这种多功能吲哚胺可以促进氧化应激的中和、调节炎症反应、防止DNA损伤，以及预防糜烂性化学战剂诱导的表观遗传机制介导的长期健康后果。在这种情况下，开发新的药剂配方以便口服和/或局部应用褪黑素用于预防糜烂性化学战剂，以及在不久的将来开发暴露后治疗方法至关重要。
