title: Comparison of enzymically glucuronidated flavonoids with flavonoid aglycones in an in vitro cellular model of oxidative stress protection.
abstract: This study modeled, in vitro, the potential effect of conjugative (phase II) metabolism on the cytoprotective capacity of fruit flavonoids against oxidative stress. Flavonoid aglycones were compared with their corresponding isomeric mixtures of glucuronides for their ability to enhance the survival of cultured human Jurkat T and neuroblastoma cells stressed with hydrogen peroxide. Various polyphenolic compounds were tested as substrates in vitro for an ovine liver glucuronyl transferase preparation. Flavonoids and their glycoside derivatives were found to be good substrates, whereas phenolic acids were either poor or nonsubstrates. Five common flavonoids were glucuronidated to prepare mixtures for bioassay testing. Glucuronidation generally weakened the cytoprotective capacities of flavonoids (in the presence of H(2)O(2)), but some compounds were weakened much more than others. The concentration that halved cell death was well below 0.5 microM for most flavonoids tested, but glucuronidation increased median effective concentration values to a range of 1-16 microM. This compares with the generally accepted physiological range (0.1-10 microM) for circulating dietary polyphenolics detected in the body. Therefore, some flavonoids may retain a reduced cytoprotective capacity in vitro, after glucuronidation, whereas others may be effectively inactivated.
authors.affiliation: The Horticulture and Food Research Institute of New Zealand, Private Bag 3123, Waikato Mail Centre, Hamilton 3240, New Zealand. dstevenson@hortresearch.co.nz
authors.forename: David E
authors.initials: DE
authors.lastname: Stevenson
authors.forename: Janine M
authors.initials: JM
authors.lastname: Cooney
authors.forename: Dwayne J
authors.initials: DJ
authors.lastname: Jensen
authors.forename: Reginald
authors.initials: R
authors.lastname: Wibisono
authors.forename: Aselle
authors.initials: A
authors.lastname: Adaim
authors.forename: Margot A
authors.initials: MA
authors.lastname: Skinner
authors.forename: Jingli
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D020719:Glucuronides / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D020719:Glucuronides; D006861:Hydrogen Peroxide