Protective role of quercetin against copper(II)-induced oxidative stress: A spectroscopic, theoretical and DNA damage study

• Published in: Food and chemical toxicology Vol. 110; pp. 340 - 350
• Main Authors: Jomova, Klaudia, Lawson, Michael, Drostinova, Lenka, Lauro, Peter, Poprac, Patrik, Brezova, Vlasta, Michalik, Martin, Lukes, Vladimir, Valko, Marian
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2017
• Subjects: Copper; Copper - chemistry; Copper - toxicity; DNA damage; DNA Damage - drug effects; DNA, Bacterial - chemistry; DNA, Bacterial - genetics; Electron Spin Resonance Spectroscopy; EPR spectroscopy; Escherichia coli - chemistry; Escherichia coli - drug effects; Escherichia coli - genetics; Escherichia coli - metabolism; Fenton reaction; Oxidative stress; Oxidative Stress - drug effects; Protective Agents - chemistry; Protective Agents - pharmacology; Quercetin; Quercetin - chemistry; Quercetin - pharmacology; Oxidative stress; Fenton reaction; Copper; DNA damage; EPR spectroscopy; Quercetin
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2017.10.042

The radical scavenging and metal chelating properties of flavonoids indicate that they may play a protective role in diseases with perturbed metal homeostasis such as Alzheimer's disease. In this work we investigated the effect of the coordination of quercetin to copper(II) in view of the formation of ROS in Cu-catalyzed Fenton reaction. ABTS and DPPH assays confirmed that the copper(II)-quercetin complex exhibits a stronger radical scavenging activity than does quercetin alone. EPR spin trapping experiments have shown that chelation of quercetin to copper significantly suppressed the formation of hydroxyl radicals in the Cu(II)-Fenton reaction. DNA damage experiments revealed a protective effect for quercetin, but only at higher stoichiometric ratios of quercetin relative to copper. DNA protective effect of quercetin against ROS attack was described by two mechanisms. The first mechanism lies in suppressed formation of ROS due to the decreased catalytic action of copper in the Fenton reaction, as a consequence of its chelation and direct scavenging of ROS by free quercetin. Since the Cu-quercetin complex intercalates into DNA, the second mechanism was attributed to a suppressed intercalating ability of the Cu-quercetin complex due to the mildly intercalating free quercetin into DNA, thus creating a protective wall against stronger intercalators. •Quercetin has potent neuroprotective effects in patients with perturbed metal homeostasis such as Alzheimer's disease.•Chelation of copper(II) by quercetin suppressed the formation of hydroxyl radicals in Cu-Fenton system.•Viscosity measurements revealed that copper-quercetin (1:2) complex intercalates into DNA.•DNA damage experiments revealed a protective effect for quercetin at higher ratios of quercetin relative to copper.•Administration of higher concentrations of quercetin to patients with AD may reflect their improved cognitive performance.