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 the structurally-related antiatherogenic drug probucol stimulate the oxygenation of mitochondrial membranes and erythrocyte ghosts by the rabbit 15-lipoxygenase as indicated by an increase in oxygen consumption as well as by an enhanced loss of polyenoic fatty acids and by the formation of specific lipoxygenase products in the membrane phospholipids. The oxygenation of linoleic acid, phospholipids and human low-density lipoproteins was not stimulated. With mitochondrial membranes, BHT causes a quenching of the 1-anilino-8-naphthalene sulfonate fluorescence. 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 lipoxygenase attack. Owing to this unexpected effect of the antioxidants, which is not related to their radical-scavenger capacity, care should be taken in interpreting experimental data on effects of BHT and probucol.
Schnurr
K
K
Institute of Biochemistry, University Clinics Charité, Humboldt University of Berlin, Germany.
Kühn
H
H
Rapoport
S M
SM
Schewe
T
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives* / Q000494:pharmacology; D002417:Cattle; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000201:enzymology; D005456:Fluorescent Dyes; D006801:Humans; D008322:Mammals; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology; D010101:Oxygen Consumption / Q000187:drug effects; D010743:Phospholipids / Q000032:analysis; D011341:Probucol / Q000494:pharmacology*; D011817:Rabbits
D000975:Antioxidants; D005456:Fluorescent Dyes; D010743:Phospholipids; D002084:Butylated Hydroxytoluene; C037667:3,5-di-tert-butyl-4-hydroxytoluene; D001093:Arachidonate 15-Lipoxygenase; D011341:Probucol