Protective effect of ebselen on cytotoxicity induced by cholestane-3 beta, 5 alpha, 6 beta-triol in ECV-304 cells.

Abstract

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.

• Authors: Qingzhi Wu, Kaixun Huang
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1761 Issue 3 Pg. 350-9 (Mar 2006) ISSN: 0006-3002 [Print] Netherlands
• PMID: 16581291 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Azoles
• Cholestanols
• Hypolipidemic Agents
• Isoindoles
• Organoselenium Compounds
• Reactive Oxygen Species
• Sulfhydryl Compounds
• cholestane-3,5,6-triol
• ebselen
• Malondialdehyde
• Glutathione

Topics

• Antioxidants (metabolism)
• Azoles (metabolism)
• Cell Line
• Cell Survival
• Cholestanols (metabolism, toxicity)
• Glutathione (metabolism)
• Humans
• Hypolipidemic Agents (metabolism, toxicity)
• Isoindoles
• Lipid Peroxidation
• Malondialdehyde (metabolism)
• Organoselenium Compounds (metabolism)
• Reactive Oxygen Species (metabolism)
• Sulfhydryl Compounds (metabolism)