title: The reversibility of the glutathionyl-quercetin adduct spreads oxidized quercetin-induced toxicity.
abstract: Quercetin is one of the most prominent dietary antioxidants. During its antioxidant activity, quercetin becomes oxidized into its o-quinone/quinone methide QQ. QQ is toxic since it instantaneously reacts with thiols of, e.g., proteins. In cells, QQ will initially form an adduct with glutathione (GSH), giving GSQ. We have found that GSQ is not stable; it dissociates continuously into GSH and QQ with a half life of 2min. Surprisingly, GSQ incubated with 2-mercapto-ethanol (MSH), a far less reactive thiol, results in the conversion of GSQ into the MSH-adduct MSQ. A similar conversion of GSQ into relatively stable protein thiol-quercetin adducts is expected. With the dithiol dihydrolipoic acid (L(SH)(2)), quercetin is formed out of GSQ. These results indicate that GSQ acts as transport and storage of QQ. In that way, the initially highly focussed toxicity of QQ is dispersed by the formation of GSQ that finally spreads QQ-induced toxicity, probably even over cells.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, University of Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands. a.boots@farmaco.unimaas.nl
authors.forename: Agnes W
authors.initials: AW
authors.lastname: Boots
authors.forename: Jiska M
authors.initials: JM
authors.lastname: Balk
authors.forename: Aalt
authors.initials: A
authors.lastname: Bast
authors.forename: Guido R M M
authors.initials: GR
authors.lastname: Haenen
mesh_terms: D005978:Glutathione / Q000032:analysis / Q000737:chemistry*; D007700:Kinetics; D008956:Models, Chemical; D010084:Oxidation-Reduction; D011794:Quercetin / Q000032:analysis / Q000737:chemistry* / Q000633:toxicity*; D013438:Sulfhydryl Compounds / Q000032:analysis / Q000737:chemistry*
chemical_list: D013438:Sulfhydryl Compounds; D011794:Quercetin; D005978:Glutathione