RESUMO
Melatonin is widely known for its antioxidant, immunomodulatory, and anti-inflammatory effects. Hypochlorous acid (HOCl) is one example of an endogenous oxidant that is promptly neutralized by melatonin. Melatonin also inhibits myeloperoxidase, the enzyme that catalyzes the oxidation of chloride to HOCl. Taurine is the most abundant free amino acid in leukocytes. In activated neutrophils, taurine is converted to taurine chloramine (Tau-NHCl) through a reaction with HOCl. In addition, the related compound taurine bromamine (Tau-NHBr) can be released by neutrophils and eosinophils. The aim of this study was to investigate the reactivity of Tau-NHCl and Tau-NHBr with melatonin. We found that melatonin can react with either Tau-NHCl or Tau-NHBr, leading to the production of 2-hydroxymelatonin and N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK). The reaction was pH-dependent, and it occurs more rapidly at a slightly acidic pH. Tau-NHBr was significantly more reactive than Tau-NHCl. Using Tau-NHBr as the oxidizing agent, 1 mm melatonin was oxidized in less than 1 min. The pH dependence of the reaction with Tau-NHCl and the increased reactivity of Tau-NHBr can be explained by a mechanism based on the initial attack of chloronium (Cl(+)) or bromonium (Br(+)) ions on melatonin. We also found that the addition of iodide to the reaction medium increased the yield of AFMK. These findings could contribute to the establishment of new functions for melatonin in inflammatory and parasitic diseases, where the role of this indoleamine has been extensively investigated.
Assuntos
Melatonina/química , Taurina/análogos & derivados , Cromatografia Líquida de Alta Pressão , Concentração de Íons de Hidrogênio , Ácido Hipocloroso/química , Iodetos/química , Iodetos/metabolismo , Cinética , Cinuramina/análogos & derivados , Cinuramina/química , Cinuramina/metabolismo , Melatonina/análogos & derivados , Melatonina/metabolismo , Oxirredução , Taurina/química , Taurina/metabolismoRESUMO
BACKGROUND: Melatonin is well-established as a powerful reducing agent of oxidant generated in the cell medium. We aimed to investigate how readily melatonin is oxidized by peroxyl radicals ROO generated by the thermolysis of 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH) and the role of glutathione (GSH) during the reaction course. METHODS: Chromatographic, mass spectroscopy, and UV-visible spectrometric techniques were used to study the oxidation of melatonin by ROO or horseradish peroxidase (HRP)/H2O2. Our focus was the characterization of products and the study of features of the reaction. RESULTS: We found that N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) and a monohydroxylated derivative of melatonin were the main products of the reaction between melatonin and ROO. Higher pH or saturation of the medium with molecular oxygen increased the yield of AFMK but did not affect the reaction rate. Melatonin increased the depletion of intracellular GSH mediated by AAPH. Using the HRP/H2O2 as the oxidant system, the addition of melatonin promoted the oxidation of GSH to GSSG. CONCLUSIONS: These results show, for the first time, that melatonin radical is able to oxidize GSH. GENERAL SIGNIFICANCE: We propose that this new property of melatonin could explain or be related to the recently reported pro-oxidant activities of melatonin.