title: Glucuronidated metabolites of the flavonoid quercetin do not auto-oxidise, do not generate free radicals and do not decrease nitric oxide bioavailability.
abstract: Quercetin, the most abundant flavonoid in the diet, reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (as the aglycone) is usually not present in plasma, but it is rapidly metabolised during absorption by methylation, glucuronidation and sulfation. Depending on the experimental conditions, quercetin can show anti-oxidant or pro-oxidant effects. We have analysed the pro-oxidant effects of quercetin and its methylated (3-methylquercetin or isorhamnetin), sulfated (quercetin 3'-sulfate), glucuronidated (quercetin 3-glucuronide) and methylated plus glucuronidated (isorhamnetin 3-glucuronide) metabolites. Auto-oxidation, O(2)(-) release and NO scavenging were analysed by means of absorption spectra, lucigenin chemiluminescence or superoxide dismutase inhibitable cytochrome C reduction and an amperometric electrode, respectively. The biological activity of NO was tested in rat aortic rings. Quercetin, isorhamnetin and quercetin 3'-sulfate auto-oxidized in aqueous buffer and generated superoxide radical. Quercetin but not the glucuronide scavenged NO. In contrast, the glucuronides were without effect. Quercetin, but not quercetin 3-glucuronide, inhibited the biological activity of NO. These data indicate that, in contrast to quercetin, its main circulating forms, i. e., the glucuronides, do not exert pro-oxidant effects.
authors.affiliation: Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Spain.
authors.forename: Federica
authors.initials: F
authors.lastname: Lodi
authors.forename: Rosario
authors.initials: R
authors.lastname: Jiménez
authors.forename: Carmen
authors.initials: C
authors.lastname: Menendez
authors.forename: Paul W
authors.initials: PW
authors.lastname: Needs
authors.forename: Juan
authors.initials: J
authors.lastname: Duarte
authors.forename: Francisco
authors.initials: F
authors.lastname: Perez-Vizcaino
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011794:Quercetin / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005609:Free Radicals; D009569:Nitric Oxide; D011794:Quercetin; D005966:Glucuronidase