title: An essential difference in the reactivity of the glutathione adducts of the structurally closely related flavonoids monoHER and quercetin.
abstract: During the scavenging of free radicals flavonoids are oxidized to electrophilic quinones. Glutathione (GSH) can trap these quinones, thereby forming GSH-flavonoid adducts. The aim of this study was to compare the stability of the GSH-flavonoid adduct of 7-mono-O-(β-hydroxyethyl)rutoside (monoHER) with that of quercetin. It was found that GSH-quercetin reacts with the thiol N-acetyl-L-cysteine (NAC) to form NAC-quercetin, whereas GSH-monoHER does not react with NAC. In addition, the adduct of the monoHER quinone with the dithiol dithiothreitol (DTT) is relatively stable, whereas the DTT-quercetin adduct is readily converted into quercetin and DTT disulfide. These differences in reactivity of the thiol-flavonoid adducts demonstrate that GSH-monoHER is much more stable than GSH-quercetin. This difference in reactivity was corroborated by molecular quantum chemical calculations. Thus, although both flavonoid quinones are rapidly scavenged by GSH, the advantage of monoHER is that it forms a stable conjugate with GSH, thereby preventing a possible spread of toxicity. These findings demonstrate that even structurally comparable flavonoids behave differently, which will be reflected in the biological effects of these flavonoids.
authors: Department of Toxicology, NUTRIM School for Nutrition, Toxicology, and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands. hilde.jacobs@maastrichtuniversity.nl
authors: Hilde
authors: H
authors: Jacobs
authors: Mohamed
authors: M
authors: Moalin
authors: Marike W
authors: MW
authors: van Gisbergen
authors: Aalt
authors: A
authors: Bast
authors: Wim J F
authors: WJ
authors: van der Vijgh
authors: Guido R M M
authors: GR
authors: Haenen
mesh_terms: D005978:Glutathione / Q000737:chemistry*; D006896:Hydroxyethylrutoside / Q000031:analogs & derivatives* / Q000737:chemistry; D015394:Molecular Structure; D011794:Quercetin / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: C522803:7-monohydroxyethylrutoside; D006896:Hydroxyethylrutoside; D013438:Sulfhydryl Compounds; D011794:Quercetin; D005978:Glutathione