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

Eva Ramos, Emilio Gil-Martín, Cristóbal De Los Ríos, Javier Egea, Francisco López-Muñoz, René Pita, Antonio Juberías, Juan J. Torrado, Dolores R. Serrano, Russel J. Reiter, Alejandro Romero

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Article number397
Issue number2
StatePublished - Feb 2023


  • DNA damage
  • NLRP3 inflammasome
  • melatonin
  • melatonin metabolites
  • oxidative stress
  • sulfur and nitrogen mustard

ASJC Scopus subject areas

  • Food Science
  • Molecular Biology
  • Physiology
  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology


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