title: Bioavailable flavonoids to suppress the formation of 8-OHdG in HepG2 cells.
abstract: Antioxidative flavonoids, ubiquitously included in vegetables, fruits and teas, are expected to prevent degenerative diseases. It is unclear, however, whether flavonoids can enter the cellular nuclei and suppress the oxidative damage of DNA. Here, several flavonoids at the physiological concentration of 10 microM were dosed to 2.5x10(7) HepG2 cells. The nuclei were isolated and determined in the incorporated flavonoid levels, and simultaneously exposed to reactive oxygen generated from 25 mM of 2,2'-azobis(2-amidinopropane) dihydrochloride. Most of the tested flavonoids were incorporated into the cells in the range between 1000 and 1600 pmol/10(7) cells, and were in the nuclei at 250-450 pmol/10(7) cells at the maximum incorporation after 30min of cell incubation. In the cells, 23% of quercetin (3,5,7,3',4'-OH) and 8% of luteolin (5,7,3',4'-OH) were the original aglycone forms and the others were the methylated and gulucuronide/sulfate conjugates, while 72% of kaempferol (3,5,7,4'-OH) and 85% of apigenin (5,7,4'-OH) were aglycones and located in the nuclei at the similar ratio of metabolites. Quercetin and luteolin significantly suppressed the formation of 8-oxo-7,8-dihydrodeoxyguanosine by 25% and 15%, respectively, compared to those in 0-time incubated cells with the flavonoids. Under such conditions of low level and hydroxyl-masked in the nuclei, the limited flavonoids were bioavailable antioxidants to prevent genetic damage and they were B-ring catechols such as quercetin and luteolin.
authors.affiliation: Department of Biofunctional Chemistry, Graduate School of Science and Technology, Kobe University, Rokkodai, Nada, Kobe, Hyogo 657-8501, Japan. kazuki@kobe-u.ac.jp
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kanazawa
authors.forename: Mari
authors.initials: M
authors.lastname: Uehara
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yanagitani
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics; D001682:Biological Availability; D045744:Cell Line, Tumor; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D018197:Hepatoblastoma / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine