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JackD 1: Ann N Y Acad Sci. 2004 Dec;1031:127-42. Tocotrienol: the natural vitamin E to defend the nervous system? Sen CK, Khanna S, Roy S. Davis Heart & Lung Research Institute, 473 West 12th Avenue, The Ohio State University Medical Center, Columbus, Ohio 43210, USA. sen-1@medctr.osu.edu Vitamin E is essential for normal neurological function. It is the major lipid-soluble, chain-breaking antioxidant in the body, protecting the integrity of membranes by inhibiting lipid peroxidation. Mostly on the basis of symptoms of primary vitamin E deficiency, it has been demonstrated that vitamin E has a central role in maintaining neurological structure and function. Orally supplemented vitamin E reaches the cerebrospinal fluid and brain. Vitamin E is a generic term for all tocopherols and their derivatives having the biological activity of RRR-alpha-tocopherol, the naturally occurring stereoisomer compounds with vitamin E activity. In nature, eight substances have been found to have vitamin E activity: alpha-, beta-, gamma- and delta-tocopherol; and alpha-, beta-, gamma- and delta-tocotrienol. Often, the term vitamin E is synonymously used with alpha-tocopherol. Tocotrienols, formerly known as zeta, , or eta-tocopherols, are similar to tocopherols except that they have an isoprenoid tail with three unsaturation points instead of a saturated phytyl tail. Although tocopherols are predominantly found in corn, soybean, and olive oils, tocotrienols are particularly rich in palm, rice bran, and barley oils. Tocotrienols possess powerful antioxidant, anticancer, and cholesterol-lowering properties. Recently, we have observed that alpha-tocotrienol is multi-fold more potent than alpha-tocopherol in protecting HT4 and primary neuronal cells against toxicity induced by glutamate as well as by a number of other toxins. At nanomolar concentration, tocotrienol, but not tocopherol, completely protected neurons by an antioxidant-independent mechanism. Our current work identifies two major targets of tocotrienol in the neuron: c-Src kinase and 12-lipoxygenase. Dietary supplementation studies have established that tocotrienol, fed orally, does reach the brain. The current findings point towards tocotrienol as a potent neuroprotective form of natural vitamin E. PMID: 15753140 [PubMed - indexed for MEDLINE] 1: Neuropharmacology. 2004 Nov;47(6):904-15. Alpha-tocotrienol provides the most potent neuroprotection among vitamin E analogs on cultured striatal neurons. Osakada F, Hashino A, Kume T, Katsuki H, Kaneko S, Akaike A. Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan. Oxidative stress and apoptosis play pivotal roles in the pathogenesis of neurodegenerative diseases. We investigated the effects of vitamin E analogs on oxidative stress and apoptosis using primary neuronal cultures of rat striatum. A tocotrienol-rich fraction of edible oil derived from palm oil (Tocomin 50%), which contains alpha-tocopherol, and alpha-, gamma- and delta-tocotrienols, significantly inhibited hydrogen peroxide (H2O2)-induced neuronal death. Each of the tocotrienols, purified from Tocomin 50% by high-performance liquid chromatography, significantly attenuated H2O2-induced neurotoxicity, whereas alpha-tocopherol did not. alpha-, gamma- and delta-Tocotrienols also provided significant protection against the cytotoxicity of a superoxide donor, paraquat, and nitric oxide donors, S-nitrosocysteine and 3-morpholinosydnonimine. Moreover, tocotrienols blocked oxidative stress-mediated cell death with apoptotic DNA fragmentation caused by an inhibitor of glutathione synthesis, L-buthionine-[S,R]-sulfoximine. In addition, alpha-tocotrienol, but not gamma- or delta-tocotrienol, prevented oxidative stress-independent apoptotic cell death, DNA cleavage and nuclear morphological changes induced by a non-specific protein kinase inhibitor, staurosporine. These findings suggest that alpha-tocotrienol can exert anti-apoptotic neuroprotective action independently of its antioxidant property. Among the vitamin E analogs examined, alpha-tocotrienol exhibited the most potent neuroprotective actions in rat striatal cultures. PMID: 15527824 [PubMed - indexed for MEDLINE]
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