Can nucleotides prevent Cu-induced oxidative damage?

Rozena Baruch-Suchodolsky, Bilha Fischer

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Cu-induced oxidative damage is associated with cancer, diabetes, neurodegenerative and age related diseases. The quest for Cu-chelators as potential antioxidants spans the past decades. Yet, biocompatible Cu-chelators that do not alter the normal metal-ion homeostasis are still lacking. Here, we explored the potential of natural and synthetic nucleotides and inorganic phosphates as inhibitors of the Cu(I)/(II)-induced {radical dot}OH formation via either the Fenton or Haber-Weiss mechanisms. For this purpose, we studied by ESR the modulation of Cu-induced {radical dot}OH production, from the decomposition of H2O2, by nucleotides and phosphates. ATP inhibited both Cu(I) and Cu(II) catalyzed reactions (IC50 0.11 and 0.04 mM, respectively). Likewise, adenosine 5′-β,γ-methylene triphosphate (AMP-PCP), adenosine 5′-O-(3-thiotriphosphate) (ATP-γ-S), ADP and tripolyphosphate were identified as good inhibitors. However, AMP and adenosine were poor inhibitors in the Cu(I)-H2O2 system, IC50 ca. 1.2 mM, and radical enhancers in the Cu(II)-H2O2 system. The best antioxidant was adenosine 5′-[β,γ-imino] triphosphate (AMP-PNP) (IC50 0.05 mM at Cu(I)-H2O2 system) which was 15 times more active than the known antioxidant Trolox. ATP and analogues inhibit Cu-induced {radical dot}OH formation through an ion chelation rather than a scavenging mechanism. Two phosphate groups are required for making active Fenton-reaction inhibitors. Nucleotides and phosphates triggered a biphasic modulation of the Haber-Weiss reaction, but a monophasic inhibition of the Fenton reaction. We conclude that nucleotides at sub mM concentrations can prevent Cu-induced OH radical formation from H2O2, and hence may possibly prevent oxidative damage.

Original languageEnglish
Pages (from-to)862-881
Number of pages20
JournalJournal of Inorganic Biochemistry
Issue number4
StatePublished - Apr 2008


  • Adenine nucleotides
  • Antioxidants
  • Cu(I) complexes
  • Cu(II) complexes
  • ESR


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