Inhibitory Effects of Ebselen on Lipid Peroxidation in Rat Liver Microsomes

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Abstract
The effects of ebselen(2-phenyl-1,2-benzoisoselenazol-3(2H)-one), a synthetic seleno-organic compound with glutathione peroxidase-like activity were investigated on lipid peroxidation in rat liver microsomes. Ebselen inhibited malondialdehyde production coupled to the lipid peroxidation stimulated by either ADP-iron-ascorbate or CCl4. The inhibitory activity of ebselen on each system was strongly increased by a 5-min preincubation with liver microsomes; the IC50 values against ADP-Fe-ascorbate-stimulated and CCl4-stimulated lipid peroxidation were 1.6 microM and 70 microM respectively. Ebselen also inhibited the endogenous lipid peroxidation with a NADPH-generating system, but it slightly stimulated the endogenous activity of ADP-Fe-ascorbate-stimulated lipid peroxidation (without a NADPH-generating system). Furthermore, ebselen inhibited oxygen uptake coupled to the lipid peroxidation by ADP-Fe-ascorbate and NADPH-ADP-iron; the IC50 values were 2.5 microM and 20.3 microM respectively. Ebselen also prolonged the lag-time of onset of ADP-Fe-ascorbate-stimulated lipid peroxidation significantly, but not that observed with NADPH-ADP-Fe-stimulated lipid peroxidation. These findings suggest that ebselen penetrates into the membrane lipid and acts as an effective antioxidant, and that there may be some differences between the modes of inhibitory action on the several types of lipid peroxidation.