Protective effect of ebselen against hydrogen peroxide-induced cytotoxicity and DNA damage in HepG2 cells.
The protective effect of ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), a selenoorganic compound, against hydrogen peroxide (H2O2)-induced cytotoxicity and DNA damage was investigated in a human hepatoma cell line, HepG2. The inhibitory effect of H2O2 on cell growth was determined using the tetrazolium dye colorimetric test (MTT test), and the cytotoxicity and lipid peroxidation were estimated by lactate dehydrogenase (LDH) leakage and malondialdehyde (MDA) formation, respectively. DNA damage was detected using single cell gel electrophoresis (comet assay), and intracellular reactive oxygen species (ROS) formation was measured using a fluorescent probe 2',7'-dichlorofluorescein diacetate (DCFH-DA). The results showed that H2O2 suppressed the growth of HepG2 cells and the addition of ebselen significantly reduced the suppression. Furthermore, ebselen also displayed a dose-dependent reduction of LDH leakage and MDA formation in H2O2-treated cells. The results also demonstrate that ebselen was able to reduce the ROS formation and DNA damaging effect caused by H2O2 in a dose-dependent manner. These findings suggest that ebselen has a strong protective ability against the cytotoxicity and DNA damaging effect caused by reactive oxygen species.
Yang
C F
CF
Department of Community, Occupational and Family Medicine, Faculty of Medicine, National University of Singapore, Singapore.
Shen
H M
HM
Ong
C N
CN
D001393:Azoles / Q000494:pharmacology*; D019610:Cytoprotection; D004249:DNA Damage; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors*; D054833:Isoindoles; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D016566:Organoselenium Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D001393:Azoles; D006131:Growth Inhibitors; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase