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.