title: The flavonoid 7-mono-O-(β-hydroxyethyl)-rutoside is able to protect endothelial cells by a direct antioxidant effect.
abstract: The flavonoid 7-mono-O-(β-hydroxyethyl)-rutoside (monoHER) is an effective protector against doxorubicin induced toxicity which has been related to the antioxidant activity of monoHER. The present study examines the potential relevance of the direct scavenging activity of the flavonoid. The potency of the direct antioxidant effect was confirmed by its instantaneous protection against intracellular oxidative stress in human umbilical vein endothelial cells at therapeutically achievable concentrations (EC50=60 nM) underpinning the involvement of a direct scavenging activity. This direct effect of monoHER is substantiated by (i) its site specific scavenging effect, i.e. on a molecular level monoHER is positioned at the location of radical formation, (ii) its position in the antioxidant network, i.e. on a biochemical level oxidized monoHER quickly reacts with ascorbate or glutathione, (iii) its location in the vascular system, i.e. on a cellular level monoHER is localized in the endothelial and smooth muscle cells in the vascular wall. It is concluded that the flavonoid monoHER can display a physiologically important direct antioxidant effect.
authors.affiliation: Department of Toxicology, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. Electronic address: kristien.lemmens@maastrichtuniversity.nl.
authors.forename: Kristien J A
authors.initials: KJ
authors.lastname: Lemmens
authors.affiliation: Department of Toxicology, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Bregje
authors.initials: B
authors.lastname: van de Wier
authors.affiliation: Department of Toxicology, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vaes
authors.affiliation: Department of Genetics and Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Mitrajit
authors.initials: M
authors.lastname: Ghosh
authors.affiliation: Department of Genetics and Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Marc A M J
authors.initials: MA
authors.lastname: van Zandvoort
authors.affiliation: Department of Toxicology, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Wim J F
authors.initials: WJ
authors.lastname: van der Vijgh
authors.affiliation: Department of Toxicology, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Aalt
authors.initials: A
authors.lastname: Bast
authors.affiliation: Department of Toxicology, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Guido R M M
authors.initials: GR
authors.lastname: Haenen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D006896:Hydroxyethylrutoside / Q000031:analogs & derivatives / Q000494:pharmacology; D017665:Hydroxyl Radical; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D012431:Rutin / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: C000598830:7-mono-O-(beta-hydroxyethyl)rutoside; C522803:7-monohydroxyethylrutoside; D000975:Antioxidants; D006896:Hydroxyethylrutoside; D017665:Hydroxyl Radical; D012431:Rutin
keywords: 7-Mono-O-(β-hydroxyethyl)-rutoside; Antioxidant; Flavonoid; Site specific scavenging; monoHER