Radical-trapping and preventive antioxidant effects of 2-hydroxymelatonin and 4-hydroxymelatonin: Contributions to the melatonin protection against oxidative stress

Adriana Pérez-González, Annia Galano, J. Raúl Alvarez-Idaboy, Dun Xian Tan, Russel J. Reiter

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Background Melatonin is well known for its antioxidant capacity, which has been attributed to the combined protective effects of the parent molecule and its metabolites. However, the potential role of 2-hydroxymelatonin (2OHM) and 4-hydroxymelatonin (4OHM) in such protection has not been previously investigated. Methods The calculations were performed using the Density Functional Theory, with the M05-2X and M05 functionals, the 6-311+G(d,p) basis set and the solvation model based on density (SMD). Results 4OHM shows excellent antioxidant activity via radical-trapping, reacting with peroxyl radicals faster than Trolox and melatonin. 4OHM can be moderately efficient as a preventing antioxidant by inhibiting Cu(II). This effect would lower the Cu(I) availability, which is the redox state required for the [rad]OH to be formed, via Fenton-like reactions. 4OHM turns off the oxidant effects of copper-ascorbate mixtures. The presence of a phenolic group was identified as the key structural feature in the antioxidant activity of 4OHM. On the other hand, 2OHM does not present a phenolic group, despite its formal name. Its keto tautomer was identified as the most abundant one (~ 100%). This may explain the relative low antioxidant protection of 2OHM. Conclusions 4OHM significantly contributes to the overall antioxidant activity exhibited by melatonin, while the effects of 2OHM in this context are predicted to be only minor. This low reactivity might justify the relatively large abundance of 2OHM in biological systems. General significance Hydroxylated melatonin metabolites, such as 4OHM, may play an important role in the protective effects of melatonin against oxidative stress.

Original languageEnglish (US)
Pages (from-to)2206-2217
Number of pages12
JournalBiochimica et Biophysica Acta - General Subjects
Volume1861
Issue number9
DOIs
StatePublished - Sep 2017

Keywords

  • Inhibition of [rad]OH production
  • Kinetics
  • Metal chelation
  • Reaction mechanisms
  • Solvent polarity
  • pH

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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