Tocopherols and
tocotrienols constitute the
vitamin E family. Although
alpha-tocotrienol is the most neuroprotective form of
vitamin E proved to be effective against
stroke,
alpha-tocopherol is the most abundant in nature and is used most often for disease prevention/treatment. A recent metaanalysis of human studies suggested that
alpha-tocopherol supplementation increases all-cause mortality. Therefore, we investigated the effects of
alpha-tocopherol ( approximately 44 mg/kg
body weight; equivalent to 2,600 mg/human/day) on the central nervous system (CNS) of
stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP treated with high dose
alpha-tocopherol had significantly higher blood pressure than untreated controls fed a basal diet that contained approximately 4 mg
tocopherols/kg
body weight, but neither group experienced a change in degree of lipid peroxidation in serum or CNS tissue. Biochemical/immunohistochemical analyses demonstrated that expressions of phosphorylated
neurofilament H protein,
glial fibrillary acidic protein and
cathepsin D in the CNS tissue were significantly enhanced in
alpha-tocopherol-supplemented rats, whereas expressions of SOD2 and Bcl-xL were diminished in response to
alpha-tocopherol supplementation. Similarly, the frequency of
cathepsin D-positive cells, corresponding mostly to microglial cells, was significantly increased in
alpha-tocopherol-supplemented rats.
Alpha-tocopherol supplementation also increased the number of lysosomes and
lipofuscin granules in perikarya of both hippocampal pyramidal and Purkinje cells. Furthermore,
alpha-tocopherol supplementation increased the frequency of glial filaments and
lipofuscin granules in astrocytes and lysosomes in microglial cells that were frequently occupied with phagocytosed inclusion structures. The present results are the first to suggest that a very high dose of
alpha-tocopherol supplementation increases blood pressure in SHRSP rats and influences the CNS tissue in a manner that seems adverse.