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

1
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040 Madrid, Spain
2
Faculty of Health Sciences, University Camilo José Cela, C/Castillo de Alarcón 49, Villanueva de la Cañada, 28692 Madrid, Spain
3
Neuropsychopharmacology Unit, Hospital 12 de Octubre Research Institute (i+12), Avda. Córdoba, s/n, 28041 Madrid, Spain
4
Portucalense Institute of Neuropsychology and Cognitive and Behavioural Neurosciences (INPP), Portucalense University, R. Dr. António Bernardino de Almeida 541, 4200-072 Porto, Portugal
5
Thematic Network for Cooperative Health Research (RETICS), Addictive Disorders Network, Health Institute Carlos III, MICINN and FEDER, 28029 Madrid, Spain
6
Health Research Institute, Hospital Universitario de la Princesa, 28006 Madrid, Spain
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Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, 28006 Madrid, Spain
8
AgroBioTech for Health ABH1 Group, Department of Biochemistry, Genetics and Immunology, Faculty of Biology, University of Vigo, 36310 Vigo, Spain
9
Chemical Defense Department, Chemical, Biological, Radiological, and Nuclear Defense School, Hoyo de Manzanares, 28240 Madrid, Spain
10
Department of Pharmaceutics and Food Technology, School of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
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Centro Militar de Farmacia de la Defensa (CEMILFARDEF), Base Logística de San Pedro, Colmenar Viejo, 28770 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Academic Editor: Antonella D’Anneo
Received: 16 March 2021 / Revised: 29 March 2021 / Accepted: 7 April 2021 / Published: 10 April 2021
(This article belongs to the Special Issue Novel Melatonin Based Therapies)
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. View Full-Text
Keywords: sulfur and nitrogen mustard; melatonin; oxidative stress; inflammation; DNA damage; safety; galenic formulation sulfur and nitrogen mustard; melatonin; oxidative stress; inflammation; DNA damage; safety; galenic formulation
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MDPI and ACS Style

Romero, A.; Ramos, E.; López-Muñoz, F.; De Los Ríos, C.; Egea, J.; Gil-Martín, E.; Pita, R.; Torrado, J.J.; Serrano, D.R.; Juberias, A. Toxicology of Blister Agents: Is Melatonin a Potential Therapeutic Option? Diseases 2021, 9, 27. https://0-doi-org.brum.beds.ac.uk/10.3390/diseases9020027

AMA Style

Romero A, Ramos E, López-Muñoz F, De Los Ríos C, Egea J, Gil-Martín E, Pita R, Torrado JJ, Serrano DR, Juberias A. Toxicology of Blister Agents: Is Melatonin a Potential Therapeutic Option? Diseases. 2021; 9(2):27. https://0-doi-org.brum.beds.ac.uk/10.3390/diseases9020027

Chicago/Turabian Style

Romero, Alejandro, Eva Ramos, Francisco López-Muñoz, Cristóbal De Los Ríos, Javier Egea, Emilio Gil-Martín, René Pita, Juan J. Torrado, Dolores R. Serrano, and Antonio Juberias. 2021. "Toxicology of Blister Agents: Is Melatonin a Potential Therapeutic Option?" Diseases 9, no. 2: 27. https://0-doi-org.brum.beds.ac.uk/10.3390/diseases9020027

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