3,5-DI-T-BUTYL-4-HYDROXYTOLUENE (BHT) AND PROBUCOL STIMULATE SELECTIVELY THE REACTION OF MAMMALIAN 15-LIPOXYGENASE WITH BIOMEMBRANES

The lipophilic antioxidant 3,5-di-t-butyl-4-hydroxytoluene (BHT) and t he structurally-related antiatherogenic drug probucol stimulate the ox ygenation of mitochondrial membranes and erythrocyte ghosts by the rab bit 15-lipoxygenase as indicated by an increase in oxygen consumption as well as by an enhanced loss of polyenoic fatty acids and by the for mation of specific lipoxygenase products in the membrane phospholipids . The oxygenation of linoleic acid, phospholipids and human low-densit y lipoproteins was not stimulated. With mitochondrial membranes, BHT c auses a quenching of the 1-anilino-8-naphthalene sulfonate fluorescenc e. Thus, it is suggested that the stimulation of membrane oxygenation may be due to structural changes in the membranes leading to a better susceptibility of the polyenoic fatty acid residues towards lipoxygena se attack. Owing to this unexpected effect of the antioxidants, which is not related to their radical-scavenger capacity, care should be tak en in interpreting experimental data on effects of BHT and probucol.