title: Inhibition of peroxide-induced radical generation by plant polyphenols in C6 astroglioma cells.
abstract: Plant polyphenols like flavonoids and hydroxystilbens have been found to possess radical scavenging/antioxidative activity, especially when studied in cell-free systems. A positive effect in such assays, however, does not necessarily indicate a protective activity against deleterious effects of oxidative stress in intact cells. In fact it has been shown that polyphenols can act as anti-oxidants as well as pro-oxidants. The aim of the present study was to investigate whether and with what potency selected polyphenols are able to inhibit cellular radical generation in C6 cells and whether they can induce oxidative stress themselves. Cumene hydroperoxide (CHP) was used as a model to induce radical generation which was measured by means of a fluorometric 2',7'-dichlorodihydro-fluorescein assay. CHP-induced, time and concentration dependent, a manifold increase of DCF fluorescence indicating intracellular radical generation. This process was inhibited by all the flavonoids and the hydroxystilben resveratrol, at low micromolar concentrations. The most potent compounds, luteolin and galangin, already at concentrations of 5 to 10 microM nearly completely abolished the radical generation in the presence of 500 microM CHP. The following ranking of anti-oxidative potency was obtained: luteolingalangin>kaempferol>quercetin>resveratrolgenisteintaxifolin. This ranking is completely different from that obtained by means of a trolox equivalent antioxidant capacity (TEAC) assay in a cell-free system, thus putting the biological relevance of the latter in question. Remarkably, one compound induced oxidative stress itself, namely genistein. This flavonoid inhibited the cellular radical generation in the presence of CHP while it significantly enhanced it in the absence of the peroxide.
authors.affiliation: Institute for Toxicology and Pharmacology for Natural Scientists, University Medical School Schleswig-Holstein, Campus Kiel, Brunswiker Strasse 10, 24105 Kiel, Germany. milenanr@gmx.de
authors.forename: Milena
authors.initials: M
authors.lastname: Rüweler
authors.forename: Anika
authors.initials: A
authors.lastname: Anker
authors.forename: Michael
authors.initials: M
authors.lastname: Gülden
authors.forename: Edmund
authors.initials: E
authors.lastname: Maser
authors.forename: Hasso
authors.initials: H
authors.lastname: Seibert
mesh_terms: D001254:Astrocytoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001555:Benzene Derivatives / Q000633:toxicity; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology; D047311:Luteolin / Q000494:pharmacology; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D059808:Polyphenols; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology
chemical_list: D001555:Benzene Derivatives; D005419:Flavonoids; D016166:Free Radical Scavengers; D005609:Free Radicals; D016877:Oxidants; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D013267:Stilbenes; C037032:galangin; D019833:Genistein; D047311:Luteolin; C007164:cumene hydroperoxide; D000077185:Resveratrol