Melatonin as potential candidate to prevent the toxicity induced by chemical warfare agents

Pita, René Pita; Marco‐Contelles, José; Ramos, Eva; Pino, Javier del; Romero, Alejandro

doi:10.1007/s00204-013-1111-8

Cited by 10 publications

(5 citation statements)

References 16 publications

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“…Furthermore, the prolongation of sequelae over time in a pathological network of systemic involvement [74] puts us in the position of finding antidote-based pleiotropic remedies that address the multiplicity of actions gathered by vesicants. In this regard, the spectrum of signaling deployed by melatonin and its metabolites [75,76], as well as their wide distribution in nuclei and organelles [77,78], are consistent with the countermeasures demanded by mustard-induced dysfunctionalities [79]. Specifically, this indoleamine appears to directly remove DNA damage from physical and chemical aggressors [76].…”

Section: Role Of Melatonin In Counteracting Sulfur and Nitrogen Musta...supporting

confidence: 55%

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

et al. 2023

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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. NLRP3 inflammasome is activated in response to a wide variety of infectious stimuli or cellular stressors, however, although the precise mechanisms leading to activation are not known, mustards are postulated as activators. In this regard, melatonin, through its anti-inflammatory action and NLRP3 inflammasome modulation could exert a protective effect in the pathophysiology and management of sulfur and nitrogen mustard-induced injury. The ability of melatonin to attenuate sulfur and nitrogen mustard-induced toxicity and its high safety profile make melatonin a suitable molecule to be a part of medical countermeasures against blister agents poisoning in the near future.

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Section: Role Of Melatonin In Counteracting Sulfur and Nitrogen Musta...supporting

confidence: 55%

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

et al. 2023

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“…Plant melatonin, also called 'phytomelatonin' by some authors [15], was initially studied as an interesting natural antioxidative molecule. Its presence in foodstuff of plant origin at considerable concentrations (up to mg/100 g FW) and their subsequent incorporation in the human bloodstream after the intake make it an excellent nutraceutical for humans [16][17][18][19][20][21]. Also, more recently, the possible use of melatonin-rich plants as a recovery-bioagent for chemically contaminated soils has been suggested as an innovative phytoremediation practice [22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Functions of melatonin in plants: a review

Arnao

Hernández‐Ruíz

2015

Journal of Pineal Research

718

529

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The number of studies on melatonin in plants has increased significantly in recent years. This molecule, with a large set of functions in animals, has also shown great potential in plant physiology. This review outlines the main functions of melatonin in the physiology of higher plants. Its role as antistress agent against abiotic stressors, such as drought, salinity, low and high ambient temperatures, UV radiation and toxic chemicals, is analyzed. The latest data on their role in plant-pathogen interactions are also discussed. Both abiotic and biotic stresses produce a significant increase in endogenous melatonin levels, indicating its possible role as effector in these situations. The existence of endogenous circadian rhythms in melatonin levels has been demonstrated in some species, and the data, although limited, suggest a central role of this molecule in the day/night cycles in plants. Finally, another aspect that has led to a large volume of research is the involvement of melatonin in aspects of plant development regulation. Although its role as a plant hormone is still far of from being fully established, its involvement in processes such as growth, rhizogenesis, and photosynthesis seems evident. The multiple changes in gene expression caused by melatonin point to its role as a multiregulatory molecule capable of coordinating many aspects of plant development. This last aspect, together with its role as an alleviating-stressor agent, suggests that melatonin is an excellent prospect for crop improvement.

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“…Additionally, there are no completely effective antidotes or treatments against these agents after individuals are exposed to CWAs. Considering the complexity of the physiological processes that occur after exposure to CWAs, melatonin may be a useful antidote and may provide a reasonable strategy to counteract CWA-induced injuries [32].…”

Section: Melatonin For Protection From Chemical Weaponsmentioning

confidence: 99%

The Multiple Functions of Melatonin: Applications in the Military Setting

Gancitano

Reíter

2022

Biomedicines

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The aim of this review is to provide the reader with a general overview on the rationale for the use of melatonin by military personnel. This is a technique that is being increasingly employed to manage growing psycho-physical loads. In this context, melatonin, a pleotropic and regulatory molecule, has a potential preventive and therapeutic role in maintaining the operational efficiency of military personnel. In battlefield conditions in particular, the time to treatment after an injury is often a major issue since the injured may not have immediate access to medical care. Any drug that would help to stabilize a wounded individual, especially if it can be immediately administered (e.g., per os) and has a very high safety profile over a large range of doses (as melatonin does) would be an important asset to reduce morbidity and mortality. Melatonin may also play a role in the oscillatory synchronization of the neuro–cardio–respiratory systems and, through its epigenetic action, poses the possibility of restoring the main oscillatory waves of the cardiovascular system, such as the Mayer wave and RSA (respiratory sinus arrhythmia), which, in physiological conditions, result in the oscillation of the heartbeat in synchrony with the breath. In the future, this could be a very promising field of investigation.

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Melatonin as potential candidate to prevent the toxicity induced by chemical warfare agents

Cited by 10 publications

References 16 publications

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

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

Functions of melatonin in plants: a review

The Multiple Functions of Melatonin: Applications in the Military Setting

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