title: Preventive effect of 7,8-dihydroxyflavone against oxidative stress induced genotoxicity.
abstract: We elucidated the protective effect of 7,8-dihydroxyflavone against hydrogen peroxide (H(2)O(2))-induced DNA damage. We found that 7,8-dihydroxyflavone scavenges 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and intracellular reactive oxygen species (ROS). 7,8-Dihydroxyflavone with antioxidant effect prevented the H(2)O(2)-induced cellular DNA damage, as evidenced by comet tail, 8-hydroxy-2'-deoxyguanosine (8-OHdG) content, and phospho-histone H2A.X protein expression. Hence, 7,8-dihydroxyflavone was shown to protect cell via the inhibition of apoptosis induced by H(2)O(2). This was substantiated by decreased apoptotic nuclear fragmentation, decreased sub-G(1) cell population, and decreased DNA fragmentation. Furthermore, 7,8-dihydroxyflavone activated the protein kinase B (PKB, Akt) signal pathway, which is a major survival signal pathway. In addition, LY294002, which is phosphatidylinositol 3 kinase (PI3K, upstream of Akt) inhibitor, attenuated the protective effect of 7,8-dihydroxyflavone against H(2)O(2)-induced cell damage. In conclusion, 7,8-dihydroxyflavone was shown to possess cytoprotective properties against oxidative stress by scavenging intracellular ROS and enhancing Akt activity.
authors.affiliation: School of Medicine and Applied Radiological Science Research Institute, Cheju National University, Jeju-si, Korea.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Kyoung Ah
authors.initials: KA
authors.lastname: Kang
authors.forename: Mei Jing
authors.initials: MJ
authors.lastname: Piao
authors.forename: Dong Ok
authors.initials: DO
authors.lastname: Ko
authors.forename: Zhi Hong
authors.initials: ZH
authors.lastname: Wang
authors.forename: Weon Young
authors.initials: WY
authors.lastname: Chang
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: You
authors.forename: In Kyung
authors.initials: IK
authors.lastname: Lee
authors.forename: Bum Joon
authors.initials: BJ
authors.lastname: Kim
authors.forename: Sam Sik
authors.initials: SS
authors.lastname: Kang
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001713:Biphenyl Compounds; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D020552:Comet Assay; D006224:Cricetinae; D004249:DNA Damage; D053938:DNA Fragmentation / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D047309:Flavones / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000633:toxicity; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D009153:Mutagens / Q000633:toxicity*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics*; D010851:Picrates / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C485383:6,7-dihydroxyflavone; D001713:Biphenyl Compounds; D047309:Flavones; D016166:Free Radical Scavengers; D007202:Indicators and Reagents; D009153:Mutagens; D010851:Picrates; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; C004931:1,1-diphenyl-2-picrylhydrazyl; D051058:Oncogene Protein v-akt; D003849:Deoxyguanosine