Vitamin E and stress

Abstract

I. A critical analysis of the biological antioxidant theory of vitamin E function has been made and the implications of the theory have been tested.2. When small amounts of [5-Me-'*C]a-tocopherol were present in lipid systems subject to autoxidation in vitro, it was found that, whether the tocopherol was the sole antioxidant or was in synergistic combination with a secondary antioxidant (ascorbic acid), peroxidation did not occur without concomitant destruction of the tocopherol. This was so, whether a simple fat substrate or a liver homogenate (subject to catalysis) was used. The decomposition of tocopherol took place even when the secondary antioxidant was in large excess, as would occur under physiological conditions in the vitamin E-deficient animal, and accelerated as the induction period neared its end.3. When [5-Me-14C,3H]a-tocopherol and ascorbic acid were used as a synergistic antioxidant couple in vitro, tocopherol recovered from the peroxidizing system always had the same isotopic ratio as the starting material. This means that regeneration of tocopherol by the secondary antioxidant cannot involve, as an intermediate, a tocopherol carbon radical formed by loss of hydrogen from the 5-methyl group. Such radicals probably dimerize before they can be regenerated. The same result was found when doubly labelled a-tocopherol was given to the rat and recovered later from its tissues. 4.In a series of experiments, rats were rigorously depleted of vitamin E for periods up to 7 months and then given as little as 50 pg [14C]n-a-tocopherol. They were then given, either by stomach tube daily or by dietary addition, large amounts of methyl linoleate or vitamin Efree polyunsaturated fatty acid methyl esters prepared from cod-liver oil and compared with controls given methyl oleate for up to 3 I days. When the possibility of interaction between the lipid and tocopherol in the gut was eliminated, analyses of liver, kidney, testis, adrenal, adipose tissue, whole carcass and faeces showed that there was no effect of the polyunsaturated fatty acids on either the metabolism or recovery of ['4C]or-tocopherol in any of the animals.5. When interaction between the administered fatty acid esters and tocopherol in the gut was allowed to take place, a marked destruction of [14C]a-tocopherol in the tissues was observed in animals given the polyunsaturated esters. The importance of oxidative destruction of tocopherol in the gut before absorption was demonstrated in a nutritional trial, in which codliver oil and lard were compared and the degrees of resistance of rats' erythrocytes to dialuric acid-induced haemolysis was used as an index of vitamin E depletion.6. Similar experiments with [14C]cr-tocopherol in weanling rats given large amounts of codliver oil methyl esters also showed little effect. Although there was a suggestion that prolonged feeding of partly peroxidized polyunsaturated esters could lead to a slight depression of tissue tocopherol concentrations, no significant differences were usually obtained.7. Fourteen-day-ol...

Interactions of tocopherols and ubiquinones with monolayers of phospholipids

“…Diplock, 1976). Further, the studies by Little & O'Brien (1968) showed that lipid peroxides are substrates for this enzyme. Nevertheless, the fact that the rate of destruction of trace quantities of a-[W4C]tocopherol in the tissues of vitamin E-deficient animals is not increased by dietary polyunsaturated fatty acids (Green et al, 1967) indicates that the nutritional interaction between a-tocopherol and unsaturated lipids cannot be ascribed solely to an antioxidant mechanism. On the basis of molecular-model building, it was there-fore proposed that a-tocopherol may physically stabilize biological membranes that are rich in polyunsaturated phospholipids: this stabilization might arise from interactions between the phytyl side chain of a-tocopherol and the polyunsaturated fatty acyl residues of phospholipid molecules in the hydrophobic regions of biological membranes (Lucy, 1972;Diplock & Lucy, 1973).…”

The dependence on vitamin E and selenium of drug demethylation in rat liver microsomal fractions

“…If a-tocopherol functions in the manner that we have suggested (Diplock & Lucy, 1973) to form a physicochemical interaction between its side chain and arachidonyl moieties of membrane phospholipids, then oxidative destruction of atocopherol (as suggested by McCay etal., 1971) might not necessarily occur, since the antioxidant (hydroxyl) function of tocopherol need not be involved. The failure of Green et al (1967) to demonstrate increased destruction of small amounts of 14C-labelled atocopherol in vitamin E-deficient rats given large amounts of dietary polyunsaturated fatty acids might thus be explained. Further, the possibility of accelerated breakdown of membrane-associated phospholipids by endogenous phospholipases must be considered; the expected alteration in the membrane architecture in vitamin E deficiency would be expected to lead to an increased accessibility of the substrate, polyunsaturated fatty acyl residues of membrane phospholipids, to the enzyme.…”

The nutritional and metabolic roles of selenium and vitamin E

“…If a-tocopherol functions in the manner we have suggested (Diplock & Lucy, 1973) to promote membrane stability and compactness by physical means, then destruction of or-tocopherol might not be seen as a corollary of peroxidative attack on unsaturated fatty acids. This could thus explain the failure of Green, Diplock, Bunyan, McHale & Muthy (1967) to demonstrate an increased rate of destruction of 14C-labelled a-tocopherol in rats given large amounts of PUFA. Furthermore, the possibility of accelerated breakdown of membrane-associated phospholipids by endogenous phospholipases in the absence of tocopherols must be considered (Diplock & Lucy, 1973).…”

“…I n a critical and detailed study of the antioxidant hypothesis, Green and co-workers (e.g. Green, Diplock, Bunyan, McHale & Muthy, 1967 ;Green, Diplock, Bunyan, Muthy & McHale, 1967) could find little evidence that PUFA-exacerbated vitamin E deficiency was accompanied by increased destruction of I4C-labelled a-tocopherol, or by accumulation of lipid peroxides, the two criteria that had come to be regarded as implicit in the hypothesis. I n a review of this work, Green & Runyan (1969) concluded that the results were 'contrary to the requirements of the theory'.…”