Inhibitory effect of ebselen on the oxidation of low density lipoprotein

The inhibitory effect of a synthesized glutathione peroxidase (GSHPX) mimic- ebselen, and its cofactor glutathione (GSH), on the oxidation of low density lipoprotein (LDL) induced by Cu2+ was studied by determination of hydroperoxides and thiobarbituric acid reactive substances (TBARS). Ebselen alone had a strong inhibitory effect on the oxidation of LDL. The lag time of LDL oxidation was prolonged with an increase in the concentration of ebselen. The inhibitory effect of 5 mu M ebselen was equivalent to that of 50 mu M alpha-tocopherol, When GSH was present, ebselen exhibited stronger inhibitory effect than when present alone, With 50 mu M GSH, ebselen at a concentration as low as 5 mu M could inhibit oxidation of LDL induced by 5 mu M Cu2+ completely for at least 24 h, Ebselen at high concentrations (100 mu M) decomposed hydroperorxides in pre-oxidized LDL and effectively prevented its further oxidation, but not in the present of EDTA. Low concentration of ebselen (5 mu M) plus GSH (50 mu M) decomposed hydroperoxides in pre-oxidized LDL whether EDTA was added or not.