Abstract

The effects of alpha-tocopherol and its homologues with different chain lengths (6-hydroxy-chromanes: C 1, C 6, C 11) on lipid peroxidation in natural membranes (liver microsomes and mitochondria, brain synaptosomes) and liposomes were studied. It was shown that the antioxidant activity of alphatocopherol homologues decreased in the order: C 1 > C 6 > C 11 >alpha-tocopherol (C 16). Using fluorescent measurements, the possible reasons underlying these differences were investigated: (i) the distribution between the aqueous media and nonpolar phase of the membrane, which predetermines the binding of alpha-tocopherol homologues to membranes; (ii) the incorporation of alpha-tocopherol homologues into lipid bilayer; (iii) non-uniform distribution (formation of the clusters) of tocopherol homologues in the lipid bilayer; and (iv) transbilayer mobility of alpha-tocopherol homologues and accessibility of the inhibitors for radical-generating centres under enzymically and non-enzymically induced lipid peroxidation. It was demonstrated that: (i) binding of C 1 with membranes was less efficient than that of longer-chain homologues (C 6, C 11, C 16); (ii) the level of incorporation of alpha-tocopherol homologues into membranes decreased in a succession alpha-tocopherol C 11 > C 6 > C 1; (iii) all alphatocopherol homologues existed in the lipid bilayer not only in a monomeric form but also associated in clusters thus decreasing the efficiency of radical scavenging; (iv) the short-chain alpha-tocopherol homologue, C 1, exhibited a high transbilayer mobility whereas the long-chain one, C 16, underwent no transbilayer migration within tens of minutes. The inhibiting effect of alpha-tocopherol esters and C 1-acetate was predetermined by their hydrolysis in biomembranes; a strong correlation exists between the rate of the ester hydrolysis and their antioxidant activity in the membrane. In liposomes, in which the esterase activity was absent, alpha-tocopherol esters and C 1-acetate exhibited very low lipid peroxidation inhibition.

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