Preventive effect of 7,8-dihydroxyflavone against oxidative stress induced genotoxicity.
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.
Zhang
Rui
R
School of Medicine and Applied Radiological Science Research Institute, Cheju National University, Jeju-si, Korea.
Kang
Kyoung Ah
KA
Piao
Mei Jing
MJ
Ko
Dong Ok
DO
Wang
Zhi Hong
ZH
Chang
Weon Young
WY
You
Ho Jin
HJ
Lee
In Kyung
IK
Kim
Bum Joon
BJ
Kang
Sam Sik
SS
Hyun
Jin Won
JW
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
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