The antioxidant action of a pure antioestrogen: ability to inhibit lipid peroxidation compared to tamoxifen and 17 beta-oestradiol and relevance to its anticancer potential.
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 > 17 beta-oestradiol > nafoxidine > or = 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 > 17 beta-oestradiol > ICI 164,384 > tamoxifen > or = 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 beta-oestradiol and is discussed in relation to its anticancer action.
Wiseman
H
H
Pharmacology Group, King's College, University of London, U.K.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002417:Cattle; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009256:Nafoxidine / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D051381:Rats; D013629:Tamoxifen / Q000494:pharmacology
D000970:Antineoplastic Agents; D000975:Antioxidants; D005290:Ferric Compounds; D053284:Polyunsaturated Alkamides; D013629:Tamoxifen; D009256:Nafoxidine; D004958:Estradiol; C051781:ICI 164384; C061126:iron(III)-ascorbic acid complex; D001205:Ascorbic Acid