The antioxidant action of a pure antioestrogen: Ability to inhibit lipid peroxidation compared to tamoxifen and 17β-oestradiol and relevance to its anticancer potential

Abstract

The pure antioestrogen ICI 164,384, and nafoxidine (structurally related to tamoxifen) were good inhibitors of iron ion-dependent lipid peroxidation. In rat liver microsomes incubated with Fe(III)-ascorbate the overall order of effectiveness of the compounds tested as inhibitors of lipid peroxidation was 4-hydroxytamoxifen > 17β-oestradiol > nafoxidine ⩾ tamoxifen > ICI 164,384. When the microsomes were incubated with Fe(III)-ADP/NADPH, a similar order of effectiveness was observed. In ox-brain phospholipid liposomes incubated with Fe(III)-ascorbate the order was 4-hydroxytamoxifen > 17β-oestradiol > ICI 164,384 > tamoxifen ⩾ nafoxidine. The antioxidant ability of ICI 164,384, a steroidal oestrogen antagonist, is compared to that of tamoxifen (a non-steroidal antioestrogen and partial oestrogen agonist) and 17 β-oestradiol and is discussed in relation to its anticancer action.