Hayton, Samantha Melanie; (2001) Longitudinal electrophysiological and biochemical studies in rats receiving different forms and intakes of vitamin E. Doctoral thesis (Ph.D), UCL (University College London.

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Abstract

Vitamin E is a generic term for a number of different chemical compounds (tocopherols and tocotrienols), with α-tocopherol (αT) having the greatest biological activity. Natural RRR-αT is a single isomer, which has a greater biological activity (assessed by the rat foetal resorption assay) than synthetic all-rac-αT, which consists of a mixture of 8 isomers. A severe and chronic deficiency of αT causes a characteristic neurological syndrome in man and rats with similar electrophysiological abnormalities. The αT deficient rat is, therefore, an appropriate model for studying a deficiency in man. Electrophysiological techniques provide a simple, objective, non-invasive measure of nerve function and were used to a) determine the minimum requirements of αT necessary to prevent neural abnormalities, b) compare the biological activities of the different forms of αT in neural tissues and c) investigate the effect of repletion of αT deficient rats. Weanling animals were fed diets containing various amounts of either all- rac- or RRR-αT acetate and longitudinal electrophysiological studies (somatosensory evoked potentials, visual evoked potentials and electroretinogram) were carried out in the same animals at monthly intervals. After 14 months the rats were killed and concentrations of αT and malondialdehyde (a measure of lipid peroxidation) determined in neural and non-neural tissues by high performance liquid chromatography. Significant electrophysiological abnormalities were seen after 8 months of deficiency. A dietary intake of 1.0-1.25mg/kg all-rac- and 0.75 mg/kg RRR-αT acetate appeared to provide only marginal protection in preventing these abnormalities. The minimum requirement to prevent the development of all neural abnormalities is between 1.25 and 5mg/kg αT acetate. These results indicated that the biological activity of all-rac-αT in neural tissues was approximately 75% of that of RRR-α, which is similar to that previously shown using rat foetal resorption assays. The tissue αT concentrations showed the expected gradient with increasing dietary intake, with neural tissues tending to conserve αT. The concentration of free MDA was significantly increased in deficient compared to control animals in all tissues. The repleted group showed significant improvements in electrophysiological parameters compared to deficient rats after 6 weeks of repletion, indicating that repletion had halted neural degeneration. The results of this study are consistent with αT deficiency causing increased lipid peroxidation, leading to abnormal neural electrophysiology.

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