title: The flavanol (-)-epicatechin and its metabolites protect against oxidative stress in primary endothelial cells via a direct antioxidant effect.
abstract: Accumulating evidence suggests that foods rich in flavanols decrease the risk of developing cardiovascular diseases. Attenuation of oxidative stress was suggested to contribute to the cardiovascular benefit of flavanols. Up to now it was unclear whether flavanol metabolites can also protect cells from oxidative stress. The aim of the present study was to determine the potential contribution of several glucuronidated, methylated and sulfated metabolites of (-)-epicatechin (EC) and (+)-catechin (Cat) to the protection of human vascular endothelial cells (HUVECs) against oxidative stress. The relative potency of the tested compounds to scavenge superoxide anion radicals showed that a free catechol moiety in the molecule is important for the direct antioxidant activity. EC and Cat (0.5, 1, 10µM) were potent radical scavengers and provided protection against intracellular oxidative stress induced by hydrogen peroxide. Although the metabolites provided less intracellular protection compared to EC and Cat, the tested methylated and glucuronidated metabolites reduced oxidative stress significantly in HUVECs. Our results indicate that the metabolites have a relevant contribution in the intracellular protection of EC and Cat against oxidative stress. Also, the direct antioxidant activity plays an important role in this protection.
authors.affiliation: Department of Toxicology, Maastricht University, Maastricht, The Netherlands. e.ruijters@maastrichtuniversity.nl
authors.forename: Erik J B
authors.initials: EJ
authors.lastname: Ruijters
authors.forename: Antje R
authors.initials: AR
authors.lastname: Weseler
authors.forename: Cécile
authors.initials: C
authors.lastname: Kicken
authors.forename: Guido R M M
authors.initials: GR
authors.lastname: Haenen
authors.forename: Aalt
authors.initials: A
authors.lastname: Bast
mesh_terms: D002392:Catechin / Q000378:metabolism* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D016166:Free Radical Scavengers / Q000378:metabolism* / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D013481:Superoxides; D002392:Catechin; D006861:Hydrogen Peroxide; D006419:Heme Oxygenase (Decyclizing)
keywords: Antioxidant; DCFH assay; HUVEC; Nrf2; ROS