Antioxidant properties of the melatonin metabolite N1-acetyl-5-methoxykynuramine (AMK): scavenging of free radicals and prevention of protein destruction

Redox Rep. 2003;8(4):205-13. doi: 10.1179/135100003225002709.

Abstract

In numerous experimental systems, the neurohormone melatonin has been shown to protect against oxidative stress, an effect which appears to be the result of a combination of different actions. In this study, we have investigated the possible contribution to radical scavenging by substituted kynuramines formed from melatonin via pyrrole ring cleavage. N1-Acetyl-5-methoxykynuramine (AMK), a metabolite deriving from melatonin by mechanisms involving free radicals, exhibits potent antioxidant properties exceeding those of its direct precursor N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and its analog N1-acetylkynuramine (AK). Scavenging of hydroxyl radicals was demonstrated by competition with ABTS in a Fenton reaction system at pH 5 and by competition with DMSO in a hemin-catalyzed H2O2 system at pH 8. Under catalysis by hemin, oxidation of AMK was accompanied by the emission of chemiluminescence. AMK was a potent reductant of ABTS cation radicals, but, in the absence of catalysts, a poor scavenger of superoxide anions. In accordance with the latter observation, AMK was fairly stable in a pH 8 H2O2 system devoid of hemin. Contrary to AFMK, AMK was easily oxidized in a reaction mixture generating carbonate radicals. In an oxidative protein destruction assay based on peroxyl radical formation, AMK proved to be highly protective. No prooxidant properties of AMK were detected in a sensitive biological test system based on light emission by the bioluminescent dinoflagellate Lingulodinium polyedrum. AMK may contribute to the antioxidant properties of the indolic precursor melatonin.

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Dinoflagellida / metabolism
  • Free Radical Scavengers / metabolism*
  • Free Radicals / metabolism*
  • Hemin / metabolism
  • Hydrogen Peroxide / chemistry
  • Hydrogen Peroxide / metabolism
  • Kynuramine / analogs & derivatives*
  • Kynuramine / chemistry
  • Kynuramine / metabolism*
  • Luminescence
  • Melatonin / chemistry
  • Melatonin / metabolism*
  • Molecular Structure
  • Oxidants / chemistry
  • Oxidants / metabolism
  • Oxidation-Reduction
  • Oxidative Stress

Substances

  • Antioxidants
  • Free Radical Scavengers
  • Free Radicals
  • Oxidants
  • Kynuramine
  • N-acetyl-5-methoxy kynurenamine
  • Hemin
  • Hydrogen Peroxide
  • Melatonin