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Study of the oxidation of melatonin, its precursors and its catabolism products by the phagocytes-generated oxidants: taurine-chloramine and taurine-bromamine

Abstract

A very large body of evidence indicates the anti-inflammatory and immunomodulatory properties of melatonin. Its mechanism of action includes the inhibition of pro-inflammatory cytokines, cyclooxygenases, nitric oxide synthase, and antioxidants enzymes. The myeloperoxidase (MPO) role as an enzyme involved in tissular damage through hypochlorous acid production is totally recognized by the scientific community. For instance, the discovery that the plasmatic level of MPO could be the best predictive biomarker of cardiovascular events, reinforce the importance of this enzyme in the genesis or progression of many inflammatory diseases. Taurine-chloramine is among the main products generated during activation of neutrophils through the catalytic activity of MPO. Recently, the properties of taurine-chloramine as an immunomodulatory molecule have been demonstrated. In this context, this project aims the study of the interrelation melatonin/MPO as follows: The study of the reactivity between melatonin and taurine-chloramine and melatonin and taurine-bromamine. The last endogenous oxidant is produced by eosinophil peroxidase (EPO); ii) these studies will be also performed with the melatonin precursors, tryptophan and serotonin, and with the catabolism melatonin products N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N-acetyl-5-methoxykynuramine AMK; iii) since melatonin is recognized as an excellent inhibitor of MPO, we aim to study the inhibitory effect of the melatonin products regarding the MPO activity. (AU)

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