Skip to main content

Dietary vitamin E, brain redox status and expression of Alzheimer's disease-relevant genes in rats

  • Sonja Gaedicke (a1), Xiangnan Zhang (a2), Patricia Huebbe (a1), Christine Boesch-Saadatmandi (a1), Yijia Lou (a2), Ingrid Wiswedel (a3), Andreas Gardemann (a3), Jan Frank (a1) and Gerald Rimbach (a1)...

Oxidative stress is one of the major pathological features of Alzheimer's disease (AD). Here, we investigated whether dietary vitamin E (VE) depletion may induce adverse effects and supplementation with α-tocopherol (αT) may result in beneficial effects on redox status and the regulation of genes relevant in the pathogenesis of AD in healthy rats. Three groups of eight male rats each were fed diets with deficient ( < 1 mg αT equivalents/kg diet), marginal (9 mg αT equivalents/kg diet) or sufficient (18 mg αT equivalents/kg diet) concentrations of natural-source VE for 6 months; a fourth group was fed the VE-sufficient diet fortified with αT (total VE, 146 mg αT equivalents/kg diet). Feeding of the experimental diets dose dependently altered αT concentrations in the cortex and plasma. No significant changes in F2-isoprostane concentrations, activities of antioxidative enzymes (total superoxide dismutase, Se-dependent glutathione peroxidase) and concentrations of glutathione or the expression of AD-relevant genes were observed. In this non-AD model, depletion of VE did not induce adverse effects and supplementation of αT did not induce positive effects on the parameters related to the progression of AD.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Dietary vitamin E, brain redox status and expression of Alzheimer's disease-relevant genes in rats
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Dietary vitamin E, brain redox status and expression of Alzheimer's disease-relevant genes in rats
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Dietary vitamin E, brain redox status and expression of Alzheimer's disease-relevant genes in rats
      Available formats
Corresponding author
*Corresponding author: Gerald Rimbach, fax +49 431 880 26 28, email
Hide All
1Christen, Y (2000) Oxidative stress and Alzheimer disease. Am J Clin Nutr 71, 621S629S.
2Engelhart, MJ, Geerlings, MI, Ruitenberg, A, et al. (2002) Dietary intake of antioxidants and risk of Alzheimer disease. J Am Med Assoc 287, 32233229.
3Morris, MC, Beckett, LA, Scherr, PA, et al. (1998) Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease. Alzheimer Dis Assoc Disord 12, 121126.
4Morris, MC, Evans, DA, Tangney, CC, et al. (2005) Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. Am J Clin Nutr 81, 508514.
5Food and Nutrition Board of the Institute of Medicine (2000) Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press.
6Fillenbaum, GG, Kuchibhatla, MN, Hanlon, JT, et al. (2005) Dementia and Alzheimer's disease in community-dwelling elders taking vitamin C and/or vitamin E. Ann Pharmacother 39, 20092014.
7Petersen, RC, Thomas, RG, Grundman, M, et al. (2005) Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med 352, 23792388.
8Sano, M, Ernesto, C, Thomas, RG, et al. (1997) A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med 336, 12161222.
9Onofrj, M, Thomas, A, Luciano, AL, et al. (2002) Donepezil versus vitamin E in Alzheimer's disease: Part 2: mild versus moderate-severe Alzheimer's disease. Clin Neuropharmacol 25, 207215.
10Lampi, AM, Hopia, A, Ekholm, P, et al. (1992) Method for the preparation of triacylglycerol fractions from rapeseed and other oils for autoxidation studies. Food Sci Technol 25, 386388.
11National Research Council Nutrient Requirements of the Laboratory Rat (1995) Nutrient Requirements of Laboratory Animals, pp. 1179. Washington, DC: National Academic Press.
12Wiswedel, I, Hirsch, D, Kropf, S, et al. (2004) Flavanol-rich cocoa drink lowers plasma F(2)-isoprostane concentrations in humans. Free Radic Biol Med 37, 411421.
13Morrow, DM, Zackert, WE, Van der Ende, DS, et al. (2002) Quantification of isoprostanes as indicators of oxidant stress in vivo. In Handbook of Antioxidants, 2nd ed., pp. 5774 [E, Cadenas and L, Packer, editors]. New york: Marcel Dekker.
14Bradford, MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72, 248254.
15Marklund, S & Marklund, G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47, 469474.
16Lawrence, RA & Burk, RF (1976) Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 71, 952958.
17Tietze, F (1969) Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem 27, 502522.
18Dringen, R & Hamprecht, B (1996) Glutathione content as an indicator for the presence of metabolic pathways of amino acids in astroglial cultures. J Neurochem 67, 13751382.
19Grundman, M, Grundman, M & Delaney, P (2002) Antioxidant strategies for Alzheimer's disease. Proc Nutr Soc 61, 191202.
20Grusak, MA & DellaPenna, D (1999) Improving the nutrient composition of plants to enhance human nutrition and health. Annu Rev Plant Physiol Plant Mol Biol 50, 133161.
21Barella, L, Muller, PY, Schlachter, M, et al. (2004) Identification of hepatic molecular mechanisms of action of alpha-tocopherol using global gene expression profile analysis in rats. Biochim Biophys Acta Mol Basis Dis 1689, 6674.
22Vatassery, GT, Brin, MF, Fahn, S, et al. (1988) Effect of high doses of dietary vitamin E on the concentrations of vitamin E in several brain regions, plasma, liver, and adipose tissue of rats. J Neurochem 51, 621623.
23Martin, A, Janigian, D, Shukitt-Hale, B, et al. (1999) Effect of vitamin E intake on levels of vitamins E and C in the central nervous system and peripheral tissues: implications for health recommendations. Brain Res 845, 5059.
24Pappert, EJ, Tangney, CC, Goetz, CG, et al. (1996) Alpha-tocopherol in the ventricular cerebrospinal fluid of Parkinson's disease patients: dose-response study and correlations with plasma levels. Neurology 47, 10371042.
25Clement, M, Dinh, L & Bourre, JM (1995) Uptake of dietary RRR-alpha- and RRR-gamma-tocopherol by nervous tissues, liver and muscle in vitamin-E-deficient rats. Biochim Biophys Acta 1256, 175180.
26Handelman, GJ, Machlin, LJ, Fitch, K, et al. (1985) Oral alpha-tocopherol supplements decrease plasma gamma-tocopherol levels in humans. J Nutr 115, 807813.
27Melchert, H-U & Pabel, E (1998) The tocoperol pattern in human serum is markedly influenced by intake of vitamin E drugs – results of the German national health surveys. J Am Oil Chem Soc 75, 213216.
28Huang, HY & Appel, LJ (2003) Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans. J Nutr 133, 31373140.
29Sontag, TJ & Parker, RS (2002) Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. J Biol Chem 277, 2529025296.
30Floyd, RA & Hensley, K (2002) Oxidative stress in brain aging. Implications for therapeutics of neurodegenerative diseases. Neurobiol Aging 23, 795807.
31Morrow, JD, Hill, KE, Burk, RF, et al. (1990) A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci U S A 87, 93839387.
32Montine, KS, Quinn, JF, Zhang, J, et al. (2004) Isoprostanes and related products of lipid peroxidation in neurodegenerative diseases. Chem Phys Lipids 128, 117124.
33Cuddihy, SL, Ali, SSMusiek, ES et al. (2008) Prolonged alpha-tocopherol deficiency decreases oxidative stress and unmasks alpha -tocopherol-dependent regulation of mitochondrial function in brain. J Biol Chem 283, 69156924.
34Kolosova, NG, Shcheglova, TV, Sergeeva, SV, et al. (2006) Long-term antioxidant supplementation attenuates oxidative stress markers and cognitive deficits in senescent-accelerated OXYS rats. Neurobiol Aging 27, 12891297.
35De, AK & Darad, R (1988) Physiological antioxidants and antioxidative enzymes in vitamin E-deficient rats. Toxicol Lett 44, 4754.
36Devi, SA & Kiran, TR (2004) Regional responses in antioxidant system to exercise training and dietary vitamin E in aging rat brain. Neurobiol Aging 25, 501508.
37Tong, Y, Zhou, W, Fung, V, et al. (2005) Oxidative stress potentiates BACE1 gene expression and Abeta generation. J Neural Transm 112, 455469.
38Melo, JB, Agostinho, P & Oliveira, CR (2003) Involvement of oxidative stress in the enhancement of acetylcholinesterase activity induced by amyloid beta-peptide. Neurosci Res 45, 117127.
39Caccamo, A, Oddo, S, Sugarman, MC, et al. (2005) Age- and region-dependent alterations in Abeta-degrading enzymes: implications for Abeta-induced disorders. Neurobiol Aging 26, 645654.
40Fukami, S, Watanabe, K, Iwata, N, et al. (2002) Abeta-degrading endopeptidase, neprilysin, in mouse brain: synaptic and axonal localization inversely correlating with Abeta pathology. Neurosci Res 43, 3956.
41Calabrese, V, Scapagnini, G, Colombrita, C, et al. (2003) Redox regulation of heat shock protein expression in aging and neurodegenerative disorders associated with oxidative stress: a nutritional approach. Amino Acids 25, 437444.
42Schipper, HM, Cisse, S & Stopa, EG (1995) Expression of heme oxygenase-1 in the senescent and Alzheimer-diseased brain. Ann Neurol 37, 758768.
43Hosomi, A, Goto, K, Kondo, H, et al. (1998) Localization of alpha-tocopherol transfer protein in rat brain. Neurosci Lett 256, 159162.
44Copp, RP, Wisniewski, T, Hentati, F, et al. (1999) Localization of alpha-tocopherol transfer protein in the brains of patients with ataxia with vitamin E deficiency and other oxidative stress related neurodegenerative disorders. Brain Res 822, 8087.
45Leonard, SW, Terasawa, Y, Farese, RV Jr, et al. (2002) Incorporation of deuterated RRR- or all-rac-alpha-tocopherol in plasma and tissues of alpha-tocopherol transfer protein-null mice. Am J Clin Nutr 75, 555560.
46Hyland, S, Muller, D, Hayton, S, et al. (2006) Cortical gene expression in the vitamin E-deficient rat: possible mechanisms for the electrophysiological abnormalities of visual and neural function. Ann Nutr Metab 50, 433441.
47Rota, C, Rimbach, G, Minihane, AM, et al. (2005) Dietary vitamin E modulates differential gene expression in the rat hippocampus: potential implications for its neuroprotective properties. Nutr Neurosci 8, 2129.
48Gohil, K, Schock, BC, Chakraborty, AA, et al. (2003) Gene expression profile of oxidant stress and neurodegeneration in transgenic mice deficient in alpha-tocopherol transfer protein. Free Radic Biol Med 35, 13431354.
49Frank, J, Lundh, T, Parker, RS, et al. (2003) Dietary (+)-catechin and BHT markedly increase alpha-tocopherol concentrations in rats by a tocopherol-omega-hydroxylase-independent mechanism. J Nutr 133, 31953199.
50Frank, J, Lundh, T, Parker, RS, et al. (2003) Dietary (+)-catechin and BHT markedly increase α-tocopherol concentrations in rats by a tocopherol-ω-hydroxylase-independent mechanism. J Nutr 133, 31953199.
51Kamal-Eldin, A, Frank, J, Razdan, A, et al. (2000) Effects of dietary phenolic compounds on tocopherol, cholesterol, and fatty acids in rats. Lipids 35, 427435.
52Daniel, JW & Gage, JC (1965) The absorption and excretion of butylated hydroxytoluene (BHT) in the rat. Food Cosmet Toxicol 3, 405415.
53Thompson, JA, Bolton, JL & Malkinson, AM (1991) Relationship between the metabolism of butylated hydroxytoluene (BHT) and lung tumor promotion in mice. Exp Lung Res 17, 439453.
54Conacher, HB, Iverson, F, Lau, PY, et al. (1986) Levels of BHA and BHT in human and animal adipose tissue: interspecies extrapolation. Food Chem Toxicol 24, 11591162.
55Gaedicke, S, Zhang, X, Schmelzer, C, et al. (2008) Vitamin E dependent microRNA regulation in rat liver. FEBS Lett 582, 35423546.
56Honig, LS & Rosenberg, RN (2000) Apoptosis and neurologic disease. Am J Med 108, 317330.
57Lu, J, Moochhala, S, Kaur, C, et al. (2000) Changes in apoptosis-related protein (p53, Bax, Bcl-2 and Fos) expression with DNA fragmentation in the central nervous system in rats after closed head injury. Neurosci Lett 290, 8992.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 7
Total number of PDF views: 84 *
Loading metrics...

Abstract views

Total abstract views: 218 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 20th March 2018. This data will be updated every 24 hours.