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

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  • Zhang Rui
    School of Medicine and Applied Radiological Science Research Institute, Cheju National University
  • Kang Kyoung Ah
    School of Medicine and Applied Radiological Science Research Institute, Cheju National University
  • Piao Mei Jing
    School of Medicine and Applied Radiological Science Research Institute, Cheju National University
  • Ko Dong Ok
    School of Medicine and Applied Radiological Science Research Institute, Cheju National University
  • Wang Zhi Hong
    School of Medicine and Applied Radiological Science Research Institute, Cheju National University
  • Chang Weon Young
    School of Medicine and Applied Radiological Science Research Institute, Cheju National University
  • You Ho Jin
    Department of Pharmacology, College of Medicine, Chosun University
  • Lee In Kyung
    Department of Microbiology and Cancer Research Institute, Seoul National University College of Medicine
  • Kim Bum Joon
    Department of Microbiology and Cancer Research Institute, Seoul National University College of Medicine
  • Kang Sam Sik
    Natural Products Research Institute and College of Pharmacy, Seoul National University
  • Hyun Jin Won
    School of Medicine and Applied Radiological Science Research Institute, Cheju National University

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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.

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