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标题：Preventive Effect of 7,8-Dihydroxyflavone against Oxidative Stress Induced Genotoxicity
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作者：Rui Zhang ; Kyoung Ah Kang ; Mei Jing Piao 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2009
卷号：32
期号：2
页码：166-171
DOI：10.1248/bpb.32.166
出版社：The Pharmaceutical Society of Japan
摘要：We elucidated the protective effect of 7,8-dihydroxyflavone against hydrogen peroxide (H₂O₂)-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 H₂O₂-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 H₂O₂. This was substantiated by decreased apoptotic nuclear fragmentation, decreased sub-G₁ 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 H₂O₂-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.
关键词：7,8-dihydroxyflavone;reactive oxygen species;apoptosis;DNA damage;protein kinase B signal pathway