Preventive Effect of 7,8-Dihydroxyflavone against Oxidative Stress Induced Genotoxicity(Biochemistry)

We elucidated the protective effect of 7,8-dihydroxyflavone against hydrogen peroxide (H_2O_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_2O_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_2O_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_2O_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.