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Biological and Pharmaceutical Bulletin
Vol. 32 (2009) No. 2 P 166-171

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http://doi.org/10.1248/bpb.32.166

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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.

Copyright © 2009 The Pharmaceutical Society of Japan

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