title: The reaction of flavonoid metabolites with peroxynitrite.
abstract: There is much interest in the bioactivity of in vivo flavonoid metabolites. We report for the first time the hierarchy of reactivity of flavonoid metabolites with peroxynitrite and characterise novel reaction products. O-Methylation of the B-ring catechol containing flavonoids epicatechin and quercetin, and O-glucuronidation of all flavonoids reduced their reactivity with peroxynitrite. The reaction of the flavanones hesperetin and naringenin and their glucuronides resulted in the formation of multiple mono-nitrated and nitrosated products. In contrast, the catechol-containing flavonoids epicatechin and quercetin yielded oxidation products which when trapped with glutathione led to the production of glutathionyl-conjugates. However, the O-methylated metabolites of epicatechin yielded both mono- and di-nitrated products and nitrosated metabolites. The 3'-O-methyl metabolite of quercetin also yielded a nitrosated species, although its counterpart 4'-O-methyl quercetin yielded only oxidation products. Such products may represent novel metabolic products in vivo and may also express cellular activity.
authors.affiliation: Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading RG2 6AP, UK.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Pollard
authors.forename: Gunter G C
authors.initials: GG
authors.lastname: Kuhnle
authors.forename: David
authors.initials: D
authors.lastname: Vauzour
authors.forename: Katerina
authors.initials: K
authors.lastname: Vafeiadou
authors.forename: Xenofon
authors.initials: X
authors.lastname: Tzounis
authors.forename: Matthew
authors.initials: M
authors.lastname: Whiteman
authors.forename: Catherine
authors.initials: C
authors.lastname: Rice-Evans
authors.forename: Jeremy P E
authors.initials: JP
authors.lastname: Spencer
mesh_terms: D005419:Flavonoids / Q000737:chemistry*; D009566:Nitrates / Q000737:chemistry*; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000737:chemistry*
chemical_list: D005419:Flavonoids; D009566:Nitrates; D030421:Peroxynitrous Acid