Protective effect of ebselen on cytotoxicity induced by cholestane-3 beta, 5 alpha, 6 beta-triol in ECV-304 cells.
The protective effect of ebselen, with documented glutathione peroxidase-like activity and antioxidative and anti-inflammatory properties, on the cytotoxicity induced by oxysterol was investigated in ECV-304 cells with cholestane-3beta, 5alpha, 6beta-triol (3-triol), one of the most toxic oxysterols. 3-triol exhibited significant cytotoxicity to ECV-304 cells in dose- and time-dependent manners. Pre-incubations with ebselen at different concentrations for 4 h effectively inhibited the decreases of the cell viability and the intracellular thiols level induced by 3-triol; suppressed the 3-triol-caused increases of the GPx and NOS activities, the LDH leakage and MDA formation. The inhibition of ebselen to the generation of intracellular ROS induced by 3-triol was monitored by luminol-, lucigenin-derived chemiluminescence and DCFH-DA-derived fluorescence assays. Our results suggest that ebselen inhibited 3-triol-induced enhancement of intracellular ROS level and the cytotoxicity of 3-triol is contributed to, for the most part, an enhanced formation of intracellular O2.-; nevertheless, the mitochondria were not the main source of intercellular O2.- contributed to the cytotoxicity of 3-triol. Ebselen lost its high protection against 3-triol-induced injuries in the presence of GSH probably due to the formation of the ebselen-GSH adduct. In conclusion, our investigations provide new utility for ebselen as a prospective antiatherosclerotic in both clinical and non-clinical situations.
Wu
Qingzhi
Q
Department of Chemistry, Huazhong University of Science and Technology, Wuhan 430074, PR China.
Huang
Kaixun
K
D000975:Antioxidants / Q000378:metabolism*; D001393:Azoles / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D002777:Cholestanols / Q000378:metabolism / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000378:metabolism / Q000633:toxicity*; D054833:Isoindoles; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000378:metabolism; D016566:Organoselenium Compounds / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000975:Antioxidants; D001393:Azoles; D002777:Cholestanols; D000960:Hypolipidemic Agents; D054833:Isoindoles; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; C000474:cholestane-3,5,6-triol; C042986:ebselen; D008315:Malondialdehyde; D005978:Glutathione