---2004---
☻ Seeking to Unravel the Enigma of Vitamin E -PDF file
Karen Hopkin, Ph.D., biochemistry, is a freelance writer from Somerville, MA. She also is coauthor of the textbook Essential Cell Biology (Garland Science, 2004).
Vitamin E appears to regulate the activity of genes involved in cell adhesion, cell division, and cell signaling. And it could dampen inflammation.
FAO/WHO expert consultation on human vitamin and mineral requirement
Summary of the role of vitamin E in human metabolic processes
A large body of scientific evidence indicates that reactive free radicals are involved inmany diseases, including heart disease and cancers (1). Cells contain many potentiallyoxidizable substrates such as polyunsaturated fatty acids (PUFAs), proteins, and DNA.Therefore, a complex antioxidant defence system normally protects cells from the injuriouseffects of endogenously produced free radicals as well as from species of exogenous originsuch as cigarette smoke and pollutants. Should our exposure to free radicals exceed theprotective capacity of the antioxidant defence system, a phenomenon often referred to asoxidative stress (2), then damage to biologic molecules may occur. There is considerableevidence that disease causes an increase in oxidative stress; therefore, consumption of foodsrich in antioxidants, which are potentially able to quench or neutralise excess radicals, mayplay an important role in modifying the development of such diseases
☻ VITAMIN E SHOWN TO HELP FIGHT UPPER RESPIRATORY TRACT INFECTIONS, ESPECIALLY COLDS, IN THE ELDERLY-PDF file
WASHINGTON, D.C., August 17, 2004 – Vitamin E supplementation has potential benefit in fighting upper respiratory tract infections such as colds in the elderly, says a study published in the Aug. 18 issue of JAMA. According to the Council for Responsible Nutrition (CRN), one of the dietary supplement industry’s leading trade associations, this is one more positive study to add to the mounting scientific evidence that vitamin E is beneficial for improved immune function in the elderly. ... ...
☻ VITAMIN E DEFICIENCY IN THE MONKEY-PDF file
I. MUSCULAR DYs~oP~Y, I-Im~TOLOOIC CH~2~OES, AND Xm~ EXC~TION OF URINARY NITROGENOUS CONSTITueNTS* BY JAMES S. DINNING,$ P-.D., AND PAUL L. DAY, ProD.
(From the Department of Biockeraistry, School of Medicine, University o/Arkansas,
Little Rock)
(Received for publication, January 12, 1957)
Vitamin E has been shown to be required by a large number of species of animals (1). The most common deficiency signs are reproductive difficulties and degeneration of the skeletal muscle. The latter condition, referred to as nutritional muscular dystrophy (2), is especially prominent in vitamin E-deficient herbivorous animals. Prior to our recent brief papers (3-5) there had appeared no report of the development of clear cut vitamin E deficiency in the monkey. Mason and associates (6, 7) have reported the results of long term feeding of diets low in tocopherol to monkeys. Three animals, sacrificed after more than 2 years of feeding, exhibited skeletal muscle pathology which was considered to indicate vitamin E deficiency. Electrocardiographic changes were also observed in other monkeys fed the diet low in vitamin E but no other deficiency signs were observed. The present report describes experiments in which monkeys were fed a purified diet devoid of vitamin E. After from 6 to 13 months all the animals developed acute vitamin E deficiency. The signs of vitamin E deficiency in the monkey include muscular dystrophy; elevated urinary excretion of creatine, allantoin, and free amino acids; decreased urinary excretion of creatinine; anemia and granulocytosis. All these signs are reversed by treatment with alpha tocopherol.
☻ Synergistic effect of vitamin E and selenium in human prostate cancer cell lines-PDF file
V Venkateswaran1, NE Fleshner2 & LH Klotz
1Division of Urology, Sunnybrook and Women’s College Health Science Centre, Toronto, Ontario, Canada; and 2Division of Urology, The Princess Margaret Hospital, Ontario, Canada
Prostate Cancer and Prostatic Diseases (2004) 7, 54–56. doi:10.1038/sj.pcan.4500707
Vitamin E and selenium are the two most popular dietary supplements used to prevent prostate cancer. The hypothesis that these antioxidants reduce prostate risk is being tested in the selenium and vitamin E chemoprevention trial (SELECT). We hypothesize that selenium potentiates vitamin E-induced inhibition of prostate cancer cell growth in vitro. Prostate cancer cell populations growing asynchronously were treated with a combination of vitamin E and selenium and processed for flow cytometric analysis. Prostate cancer cells treated with a combination of the antioxidants revealed that selenium potentiates vitamin Einduced inhibition of LNCaP cells in vitro. This was demonstrated by a reduction in the percentage of cells in the S phase. This crucial finding confirms our previous observations that antioxidant molecules act via distinct mechanistic pathways. These independent biological effects can be exploited in order to augment the anticancer properties of individual agents. These data also validate the two factorial design of the SELECT trial, permitting pairwise comparisons between agents in combination and alone.
Keywords: vitamin E; selenium; prostate cancer; prevention
☻ Tamoxifen and vitamin E treatments delay symptoms in the mouse model of Niemann-Pick C-PDF file
Eric C. Bascu_an-Castillo1, Robert P. Erickson2, Christy M. Howison1, Robert J. Hunter2, Randall H. Heidenreich2, Chad Hicks3, Theodore P. Trouard4, Robert J. Gillies2,4
1 Department of Biochemistry and Molecular Biophysics, 2 Department of Pediatrics, 3 Optical Sciences Center, 4 Biomedical Engineering Program, University of Arizona, Tucson, Arizona, USA
J. Appl. Genet. 45(4), 2004, pp. 461-467
Abstract. Niemann-Pick C disease (NPC) is an irreversible neurodegenerative disorder without current treatment. It is the result of deficient intracellular cholesterol movement. We investigated the effects of tamoxifen and vitamin E (D-alpha tocopherol) treatment on patterns of weight loss and motor function in the mouse model of Niemann-Pick C disease (Npc1-/- mice). Tamoxifen has multiple metabolic effects, including reducing oxidative damage, while vitamin E primarily has this property. Npc1-/- mice were identified and treatment was initiated at an approximate age of 21 days. Tamoxifen suspended in peanut oil was administered via intraperitoneal injection (weekly, at a dose calculated to deliver 0.023 ìg/g/day). Vitamin E (25 IU) was administered orally via gavage once a week. Weight loss and Rota-Rod performance were analyzed by using Kaplan-Meyer survival curves. Tamoxifen treatment by itself significantly delayed weight loss (an endpoint of neurodegeneration) in male and female mice compared to untreated controls. Motor function was evaluated by performance on a Rota-Rod. Tamoxifen maintained Rota-Rod performance for about an extra week. Vitamin E treatment significantly delayed weight loss in females only. Rota-Rod performance was maintained slightly longer in mice treated with vitamin E. Simultaneous use of both treatments did not delay weight loss longer than tamoxifen-only treatment but had a greater effect than either treatment alone on Rota-Rod performance and demonstrated a significant positive effect on the early “learning curve” portion of the Rota-Rod evaluations. We found significant but relatively small improvements in rate of disease progression by treating Npc1-/- mice with tamoxifen and/or vitamin E. Some sex differences in response and an early improvement in Rota-Rod performance suggest areas for further study.
Key words: mice, neurodegeneration, Niemann-Pick C, Rota-Rod, tamoxifen, vitamin E.
☻ The Antioxidant Effect of Vitamin E on Plant and Animal Tissues -PDF file
Lusha W. Liang
CALIFORNIA STATE SCIENCE FAIR 2004 PROJECT SUMMARY
Objectives/Goals
The objective of this experiment is to study the effectiveness of vitamin E on the reduction of oxidation of plant and animal tissues by an oxidizing solution in a controlled environment.
Methods/Materials
I soaked one rose petal in oxidizing solution (H(2)O(2)) and soaked another in oxidizing solution but stirred in water soluble vitamin E gels. A rose petal was also submerged in H(2)O, another in H2O with vitamin E, one in H(2)0 and starch, and the last in H(2)O(2) and starch. I then observed the damage of each rose petal underneath the microscope, took a picture, and estimated the percentage of damaged areas. The same was done for fresh salmon tissue. The color changes was measured quantitatively using the HSV color wheel.
Results
At most, the rose petal soaked in vitamin E and H(2)O(2) solution was 58.7% less damaged than the rose petal soaked in H(2)O(2) alone. The presence of vitamin E in an oxidized solution reduced the effect of H(2)O(2) by about 29% for the salmon fish tissues. The presence of starch also had an effect of reducing the amount of damage from the oxidizing solution.
Conclusions/Discussion
Since the human body is such a complicated system with an extremely large number of variables, scientists carrying out studies lasting a few years still have difficulty in isolating the antioxidant effects of Vitamin E. The results of my experiment demonstrate the effectiveness of Vitamin E as an antioxidant in an controlled environment. The rose petal submerged in the solution containing vitamin E and H(2)O(2) was less affected by H(2)O(2) than the rose petal submerged in H(2)O(2) only. Plant and animal tissues in a solution of starch and H(2)O(2) were less affected by oxidation than the plant and animal tissues without starch, but more damaged than the plant and animal tissues with vitamin E and H(2)O(2). Therefore, the properties of Vitamin E were a factor for less damage on the rose petals and salmon tissues. The majority of my hypothesis was proven. However, I understimated the effect that the presence of starch would have on reducing the effect of oxidation.
☻ Synergism between Dietary Vitamin E and Exogenous Phytic Acid in Prevention of Warmed-Over Flavour Development in Chicken Breast Meat, Pectoralis major M.-PDF file
Adriana Lourenço Soares1, Rubison Olivo2,3, Massami Shimokomaki1,3 and Elza Iouko Ida1*
1 Departamento de Tecnologia de Alimentos e Medicamentos; Centro de Ciências Agrárias; Universidade Estadual de Londrina; C. P.6001; 86051-970; Londrina - PR - Brazil. 2 Globalfood Sistemas, Ingredientes e Tecnologias para Alimentos; São Paulo - SP - Brazil. 3 Faculdade de Ciências Farmacêuticas; Universidade de São Paulo; São
Paulo - SP - Brazil
ABSTRACT
The effect of α-tocopheryl acetate (AT) supplementation and exogenous application of this vitamin E associated with phytic acid (PA) on chicken breast meat WOF development was assessed. Control group was fed with 7.7IU of AT/kg of ration and supplemented group was fed with 200.0IU of AT/kg of ration. Dietary vitamin E as measured by TBARS inhibited WOF development by 78.9; 69.0; 60.7 and 46.5% (p<0.05) during storage at 6 °C for 0, 1, 3 and 5 days, respectively. This inhibition was significantly increased (p<0.05) by 86.1; 91.6; 92.9 and 95.3% during storage at 6 °C for 0, 1, 3 and 5 days, respectively, when 2mM PA was added in supplemented breast meat. In the exogenous experiment, through Response Surface Methodology design it was found out AT did not have a significant role towards oxidation inhibition whereas PA inhibited partially in samples stored for 48h at 6°C. The results showed that dietary AT inhibited at initial stage, subsequently PA would act at propagation phase occurring synergetic reaction between both antioxidants.
Key words: Warmed over flavour, vitamin E, phytic acid, lipid oxidation inhibition, response surface methodology, breast poultry meat
Harri Hemila¨ , MD, PhD; Jarmo Virtamo, MD, PhD; Demetrius Albanes, MD; and Jaakko Kaprio, MD, PhD
Background: Vitamin E and beta-carotene affect various measures of immune function and accordingly might influence the predisposition of humans to infections. However, only few controlled trials have tested this hypothesis.
Study objective: To examine whether vitamin E or beta-carotene supplementation affects the risk of pneumonia in a controlled trial.
Design and setting: The Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) study, a randomized, double-blind, placebo-controlled trial that examined the effects of vitamin E, 50 mg/d, and beta-carotene, 20 mg/d, on lung cancer using a 2 _ 2 factorial design. The trial was conducted in the general community in southwestern Finland in 1985 to 1993; the intervention lasted for 6.1 years (median). The hypothesis being tested in the present study was formulated after the trial was closed.
Participants: ATBC study cohort of 29,133 men aged 50 to 69 years, who smoked at least five cigarettes per day, at baseline.
Main outcome measure: The first occurrence of hospital-treated pneumonia was retrieved from the national hospital discharge register (898 cases).
Results: Vitamin E supplementation had no overall effect on the incidence of pneumonia (relative risk [RR], 1.00; 95% confidence interval [CI], 0.88 to 1.14) nor had _-carotene supplementation (RR, 0.98; 95% CI, 0.85 to 1.11). Nevertheless, the age of smoking initiation was a highly significant modifying factor. Among subjects who had initiated smoking at a later age (> 21 years; n _ 7,469 with 196 pneumonia cases), vitamin E supplementation decreased the risk of pneumonia (RR, 0.65; 95% CI, 0.49 to 0.86), whereas beta-carotene supplementation increased the risk (RR, 1.42; 95% CI, 1.07 to 1.89).
Conclusions: Data from this large controlled trial suggest that vitamin E and beta-carotene supplementation have no overall effect on the risk of hospital-treated pneumonia in older male smokers, but our subgroup finding that vitamin E seemed to benefit subjects who initiated smoking at a later age warrants further investigation. (CHEST 2004; 125:557–565)
Key words: alcohol; alpha-tocopherol; antioxidants; body mass index; clinical trial; coffee; cohort study; communityacquired
pneumonia; diet; risk factors
Abbreviations: ATBC _ Alpha-Tocopherol, Beta-Carotene Cancer Prevention; CI _ confidence interval; ICD _ International
Statistical Classification of Diseases, Injuries, and Causes of Death; OR _ odds ratio; RR _ relative risk
☻ Effects of vitamin E succinate on the expression of Fas and PCNA proteins in human gastric carcinoma cells and its clinical significance-PDF file
Kun Wu, Lan Zhao, Yao Li, Yu-Juan Shan, Li-Jie Wu, Department of Nutrition and Food Hygiene, School of Public Health,Harbin Medical University, Harbin 150001, Heilongjiang Province, China
World Journal of Gastroenterology 2004; 10(7): 945-949
Abstract
AIM: To investigate the effects of vitamin E succinate (VES) on the expression of Fas and PCNA proteins as well as its clinical significance in human gastric carcinoma, and to explore the mechanism of VES-induced inhibition of gastric carcinoma cell growth.
METHODS: Immunohistochemical methods were used to detect Fas and PCNA expression both in human gastric cancer SGC-7901 cells treated with VES at different doses and in human gastric carcinoma tissues.
RESULTS: After the SGC-7901 cells were treated with VES at 5, 10, 20 mg/L for 48 h, the positive rates of Fas expression were 16%, 27% and 48%, respectively, significantly increased compared to that of control group (P <0.05); while the positive rates of PCNA expression in groups treated with different doses of VES were 20%, 18% and 7%, respectively, which were significantly decreased compared to that of the control group (P<0.05). In human gastric carcinoma tissues, the Fas positive expression rate was 42.4%(25/59), which declined with the decrease in the degree of tumor differentiation (P<0.05) and with the existence of lymph node metastasis (P<0.001). While the PCNA positive expression rate was 91.5%(54/59), no relationship was observed between PCNA expression and clinicopathologic parameters.
CONCLUSION: VES inhibited the growth of gastric cancer cells by inducing Fas expression and inhibiting PCNA expression. It is, therefore, considered that the expression of Fas and PCNA genes, through tumor cell apoptosis and proliferation, respectively, may be useful as a clinical predictive index in the application of VES to gastric carcinoma therapy, where as Fas may be of more value than PCNA.
☻ Influence of parenteral administration of selenium and vitamin E during pregnancy on selected metabolic parameters and colostrums quality in dairy cows at parturition-PDF file
L. Pavlata, J. Prasek, J. Filipek, A..Pechova
Clinic of Diseases of Ruminants, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic
Vet. Med. – Czech, 49, 2004 (5): 149–155
ABSTRACT: The aim of the present work was to study the influence of different dose of parenteral administration
selenium and vitamin E in dairy cows prior to parturition on selected metabolic parameters and colostrum quality.
A total of 19 dairy cows from a farm with selenium deficiency were included in the study. The cows were divided in
3 groups (C, E1, and E2). In group E1 a product containing selenium and vitamin E (Selevit inj. a.u.v.) was administered IM four weeks prior to the expected date of parturition. In group E2 the same product was administered twice, eight and four weeks prior to parturition. Group C consisted of control animals to which no product was administered. On the day of parturition samples of blood and first colostrum were collected for laboratory examination. Concentrations of selenium were determined in blood and that of vitamin E, thyroid hormones (T3 and T4) and activities of enzymes detecting muscular damage (CK, AST, LD) were determined in serum. Colostrum was analyzed to determine the concentrations of selenium, vitamin E, immunoglobulin, as well as to determine its density. The occurrence of the disease during the first month aftter parturition was evaluated in all groups. Higher concentrations of selenium and vitamin E were found in the samples (experimental groups E1 and E2) collected on the day of parturition. Group E2 showed a significantly (P < 0.05) higher T3 concentration compared to groups C and E1 (3.05 ± 0.42 nmol/l vs 1.88 ± 0.71 and 1.81 ± 0.30 nmol/l, respectively). The same pattern was confirmed for immunoglobulin concentrations in colostrum (34.08 ± 5.93 U ZST vs 22.87 ± 5.41 and 21.38 ± 8.33 U ZST, respectively). Compared to group C, cows in group E2 also showed significantly (P < 0.05) higher concentrations of selenium in colostrum (45.43 ± 10.56 vs 29.29 ± 8.42 µg/l). The administration of selenium and vitamin E did not influence other parameters evaluated in the study. During the first 30 days of the postpartum period a trend of lower occurrence of mastitis was observed in group E2 compared to both group C and E1 (no case of mastitis compared to 5 and 4 cases of treated mastitis, respectively).
Keywords: cattle; immunoglobulins; thyroid hormones; T3; mastitis
☻ Is the Distribution of α-Tocopherol in Membranes Consistent with Its Putative Functions?-PDF file
P. J. Quinn Department of Life Sciences, King.s College London, 150 Stamford Street, London SE1 9NN, U. K.
Biochemistry (Moscow), Vol. 69, No. 1, 2004, pp. 58-66. Translated from Biokhimiya, Vol. 69, No. 1, 2004, pp. 74-84.
Abstract. Vitamin E acts as an antioxidant and stabilizer of membranes. Other functions of vitamin E unrelated to its effects on membranes are emerging. Vitamin E partitions into the lipid bilayer matrix of membranes. It orients perpendicularly to the plane of the membrane with the hydroxyl group pointing to the lipid. water interface. The vitamin is not randomly distributed in the plane of the membrane but tends to form clusters. These clusters appear to be composed of vitamin E and phosphatidylcholine in a stoichiometry of about one vitamin E per 10 phospholipid molecules. Vitamin E partitions into domains of phosphatidylcholine in model membranes formed from mixtures of phosphatidylcholine and phosphatidylethanolamine irrespective of whether the phosphatidylcholine is in the fluid or gel phase. The creation of domains enriched in vitamin E in membranes is not consistent with an antioxidant function and effects on membrane structure and stability indicate other roles of the vitamin.
Key words: α-tocopherol, phospholipid. Vitamin E complexes, X-ray diffraction, membrane structure, lipid domains
☻ ILEAL MUCOSAL EFFECTS OF VITAMIN E IN EXPERIMENTALLY INFECTED RABBITS WITH ENTEROPATHOGENIC ESCHERICHIA COLI O103-PDF file
TSALIE E.1, KALDRYMIDOY E.1, KOUZI K.2, POUTAHIDIS TH. 1, XYLOURI E.3, ILIADIS N.4,
SARRIS K.4, ABAS Z.5
1Lab. of Pathology, Veterinary Medicine, Aristotle University of Thessaloniki, Greece
2Lab. of Histology-Embryology, Medicine school, Aristotle University of Thessaloniki, Greece
3Dep. of Anatomy & Physiology of Farm Animals, Agricultural University of Athens, Greece
4Lab. or Microbiology, Veterinary Medicine, Aristotle University of Thessaloniki, Greece
5 Dep. Of Agricultural Development, Democritos Universtity of Thrace, Greece
ABSTACT
Vitamin E effect on intestinal mucosal lesions caused by E. coli infection, was examined. Sixty rabbits were challenged with the highly pathogenic strain E22 and additionally thirty of them daily administered 60 mg/kg b.w. of Vitamin E. The lesions were evaluated histologically and computer-aided morphometry was used for the following measurements: Total mucosal thickness, Villous height, Crypt depth, Villous height/crypt depth ratio, Mononuclear and Polymorphonuclear cells at the submucosa and mucosa (tip of the villous and base of the crypt). The morphometric analysis showed significant differences, indicating that vitamin E may have some beneficial effects against REPEC E22 intestinal infection.
Key words: E.coli, enteritis, vitamin E.
☻ C-Jun N-terminal kinase is required for vitamin E succinate-induced apoptosis in human gastric cancer cells-PDF file
Kun Wu, Yan Zhao, Gui-Chang Li, Wei-Ping Yu
World Journal of Gastroenterology 2004;10(8):1110-1114
Abstract
AIM: To investigate the roles of c-Jun N-terminal kinase (JNK) signaling pathway in vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells.
METHODS: Human gastric cancer cell lines (SGC-7901) were treated with vitamin E succinate (VES) at 5, 10, 20 mg/L. Succinic acid and vitamin E were used as vehicle controls and condition medium only as an untreated (UT) control. Apoptosis was observed by 4’, 6-diamidine-2’-phenylindole dihydrochloride (DAPI) staining for morphological changes and by DNA fragmentation for biochemical alterations. Western blot analysis was applied to measure the expression of JNK and phosphorylated JNK. After the cells were transiently transfected with dominant negative mutant of JNK (DNJNK) followed by treatment of VES, the expression of JNK and c-Jun protein was determined.
RESULTS: The apoptotic changes were observed after VES treatment by DNA fragmentation. DNA ladder in the 20 mg/L VES group was more clearly seen than that in 10 mg/L VES group and was not detected following treatment of UT control, succinate and vitamin E. VES at 5, 10 and 20 mg/L increased the expression of p-JNK by 2.5-, 2.8- and 4.2-fold, respectively. VES induced the phosphorylation of JNK beginning at 1.5 h and produced a sustained increase for 24 h with the peak level at 12 h. Transient transfection of DN-JNK blocked VES-triggered apoptosis by 52%. DN-JNK significantly increased the level of JNK, while decreasing the expression of VES-induced c-Jun protein.
CONCLUSION: VES-induced apoptosis in human gastric cancer SGC-7901 cells involves JNK signaling pathway via c-Jun and its downstream transcription factor.
☻ Anti-atherosclerotic effects of vitamin E - myth or reality-PDF file
Adelina Munteanu, J.-M. Zingg, A. Azzi
Institute of Biochemistry and Molecular Biology, University of Bern, Bern, Switzerland
J. Cell. Mol. Med. Vol 8, No 1, 2004 pp. 59-76
Abstract
Atherosclerosis and its complications such as coronary heart disease, myocardial infarction and stroke are the leading causes of death in the developed world. High blood pressure, diabetes, smoking and a diet high in cholesterol and lipids clearly increase the likelihood of premature atherosclerosis, albeit other factors, such as the individual genetic makeup, may play an additional role. Several epidemiological studies and intervention trials have been performed with vitamin E, and some of them showed that it prevents atherosclerosis. For a long time, vitamin E was assumed to act by decreasing the oxidation of LDL, a key step in atherosclerosis initiation. However, at the cellular level, vitamin E acts by inhibition of smooth muscle cell proliferation, platelet aggregation, monocyte adhesion, oxLDL uptake and cytokine production, all reactions implied in the progression of atherosclerosis. Recent research revealed that these effects are not the result of the antioxidant activity of vitamin E, but rather of precise molecular actions of this compound. It is assumed that specific interactions of vitamin E with enzymes and proteins are at the basis of its non-antioxidant effects. Vitamin E influences the activity of several enzymes (e.g. PKC, PP2A, COX-2, 5-lipooxygenase, nitric oxide synthase, NADPH oxidase, superoxide dismutase, phopholipase A2) and modulates the expression of genes that are involved in atherosclerosis (e.g. scavenger receptors, integrins, selectins, cytokines, cyclins). These interactions promise to reveal the biological properties of vitamin E and allow designing better strategies for the protection against atherosclerosis progression.
Keywords: vitamin E; atherosclerosis; non-antioxidant; gene expression; signaling; transcription factors; tocopherol binding proteins; clinical trials
☻ Overseas advice on preventing SARS.-PDF file
Parco M. Siu, MPhil, PhD Candidate
West Virginia University School of Medicine
Antioxidant nutraceuticals: Antioxidants are chemicals found in foods which exert a great value in strengthening our
immune system. Boost up your immune function by taking a cocktail of antioxidant supplements.
Vitamin E 1000 IU per day. Alpha-tocopherol is the biological active form of vitamin E. There are two forms of it:
d-tocopherol and dl-tocopherol. d- is the natural form and dl- is the synthetic form. Tryo get the d- form because it is
absorbed faster in our body
☻ α-Tocopherol Induces Expression of Connective Tissue Growth Factor and Antagonizes Tumor Necrosis Factor-α–Mediated Downregulation in Human Smooth Muscle Cells-PDF file
Luis Villacorta,* Aurélio V. Graça-Souza,* Roberta Ricciarelli,* Jean-Marc Zingg, Angelo Azzi
Circulation Research January 10/24, 2003
Abstract—The effect of α-tocopherol treatment on gene expression in human aortic vascular smooth muscle cells was analyzed by gene expression arrays. The expression of the connective tissue growth factor (CTGF) gene was induced by α-tocopherol 1.8-fold in gene array experiments, and similar results were also obtained by RT-PCR (1.7-fold) and at the protein level (1.4-fold). The antioxidants β-tocopherol and N-acetylcysteine did not induce CTGF gene expression, suggesting a nonantioxidant mechanism for α-tocopherol action. Protein kinase C (PKC) inhibition by α-tocopherol has been previously described. However, PKC down regulation did not prevent CTGF induction by α-tocopherol, and inhibition of PKC activity with several inhibitors did not increase its expression, suggesting an alternative pathway for the α-tocopherol effect. On the other hand, tumor necrosis factor-α reduced the expression of CTGF, an effect that was reversed by antioxidants. The data suggest that tumor necrosis factor-α inhibition of CTGF gene expression is prevented in an antioxidant-sensitive process and that α-tocopherol increases CTGF expression by a PKC-independent, nonantioxidant mechanism. Because CTGF stimulates the synthesis of extracellular matrix, the normalization of CTGF gene expression by α-tocopherol may accelerate wound repair and tissue regeneration during atherosclerosis.
Key Words: connective tissue growth factor; gene expression regulation; okadaic acid n protein kinase C; α-tocopherol; tumor necrosis factor-α
☻ Vitamin E and its effect on arterial stiffness in postmenopausal women – a randomized controlled trial-PDF file
A.H.G. Rasool1, A. Rehman2, W.N. Wan Yusuf1 and A.R.A. Rahman3
1School of Medical Sciences, 2School of Dental Sciences, and 3Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kelantan, Malaysia
In ter na tional Jour nal of Clin i cal Phar ma col ogy and Ther a peu tics, Vol. 41 – No. 12/2003 (587-592)
☻ The effect of vitamin E supplementation on discoloration of injection-site lesions in retail cuts and the greening reaction observed in injection-site lesions in muscles of the chuck1-PDF file
D. L. Roeber*2, K. E. Belk*3, T. E. Engle*, T. G. Field*, S. R. Koontz†, J. A. Scanga*, J. D. Tatum*, G. L. Mason‡, D. Van Metre§, F. B. Garry§, and G. C. Smith*
*Department of Animal Sciences; †Department of Agricultural and Resource Economics; ‡Department of Microbiology, Immunology, and Pathology; and §Department of Clinical Sciences, Colorado State University, Fort Collins 80523-1171
J. Anim. Sci. 2003. 81:1885–1894
ABSTRACT: Concern has been raised about green discoloration of injection-site lesions in chuck muscles in modified-atmosphere packages. Objectives were: 1)to recreate green lesions, 2) to compare the severity of discoloration of injection-site lesions in chucks from carcasses of control or vitamin E-supplemented steers, and 3) to identify pigment(s) responsible for discoloration via in vitro color reactions. In Exp. 1, 23 steers (BW = 415 kg; 37 d before harvest) were injected with one of 12 pharmaceuticals, following label directions for route and dose, with the exception of a 5-mL maximum dose, to identify a product that could result in discoloration. Two vaccines (Products A and B) resulted in greening. In Exp. 2, 50 steers were injected (i.m.) with Product A and assigned to the control or vitamin E (1,000 IU/steer daily for 60 d) group. After retail display, 80 and 72% of steaks from the control and treatment groups, respectively, were discolored. Although vitamin E did not reduce (P = 0.53) greening, there was a trend (P = 0.10) toward delay discoloration of lesions from the treatment group. In Phase I of Exp. 3, pigments extracted from green lesions obtained from Exp. 2 were compared with solutions, exposed to a high partial pressure of oxygen (ppO), of myoglobin (Mb), copper sulfate, hydrogen peroxide (H2O2), vaccine, and aluminum hydroxide either alone or in combination. In Phase II of Exp. 3, solutions of two or more of Mb, Cu, sodium sulfide, sodium sulfite, sodium sulfate (Na2SO4), and H2O2 were made at pH 7.2 or 5.5 and exposed to low or high ppO. Normal muscle tissue displayed a 3.2 and 56.7% decrease in absorbance/μg of protein as wavelength changed from 654 to 656 nm and 656 to 658nm, respectively. Pigments from control and treatment group green tissue displayed a 164.5 and 621.3% increase, respectively, in absorbance/μg of protein as wavelength changed from 654 to 656 nm. As wavelength changed from 656 to 658 nm, the absorbance/μg of protein for control and treatment group lesions decreased by 75 and 109%, respectively. The Mb+Cu+Na2SO4 solution, at pH 5.5 and high ppO, exhibited similar absorbance trends as green lesions indicating that greening may result from a Mb, Cu, and Na2SO4 interaction. Results indicated that greening varies with pharmaceuticals and oxidation of tissue cannot be controlled with vitamin E supplementation. Research on the causative agents of green discoloration, with an emphasis on compounds containing sulfate or Cu, is needed.
Key Words: Discoloration, Intramuscular Injection, Muscle Tissue, Subcutaneous Injection, Vitamin E
☻ VITAMIN E STATUS OF THE WEANED PIG AS A RISK FACTOR FOR DYING OF PMWS-PDF file
4th International Symposium on Emerging and Re-emerging Pig Diseases – Rome June 29th – July 2nd, 2003 220
P. Bækbo1, A-G. Hassing1, P. Olsen1, B. Lorenzen1, C. Lauridsen2
1 The National Committee for Pig Production, DANISH BACON & MEAT COUNCIL, Denmark
2Danish Institute of Agricultural Science, Foulum, Denmark.
Keywords: Vitamin E, mortality, PMWS
☻ Vegetable Oils Used as Vitamin E Vehicle Affect the Electrical Activity of the Rat Heart-PDF file
S. OZDEMIR, M. AYAZ, T. TUNCER, M. UGUR, B. TURAN
Department of Biophysics, Faculty of Medicine, Ankara University, Ankara, Turkey
Physiol. Res. 52: 767-771, 2003
Summary
The aim of this study is to define the possible effects of vegetable oils used as vitamin E vehicle on the electrical activity of the rat heart. To test the possible effects of vitamin E vehicles we studied the effect of i.p. injected corn oil, hazelnut oil or peanut oil on the action potential parameters recorded in both papillary and left atrial muscle strips. Four experimental groups were used. The control group was injected (i.p.) with distilled water, while the three remaining groups received injections of corn oil, hazelnut oil, or peanut oil for five weeks (in a dose of 0.4 ml/kg/day . minimum amount of oil in which vitamin E could be dissolved). We used borosilicated (15-20 MΩ) capillary electrodes and intracellular action potentials (AP) were recorded in isolated papillary and left atrium muscle strips. While administration of three different types of vegetable oil had no significant effect on AP parameters of papillary muscle, they significantly prolonged the repolarization phase of AP in atrial strips. These results show that vegetable oils used as vitamin E vehicles may alter the electrical activity of the heart in a tissue-dependent manner. The present data indicate that the possible effect of vegetable oil vehicles should be kept in mind while evaluating the possible effects of in vivo vitamin E administration.
Key words
Action potential Vitamin E Corn oil Peanut oil Hazelnut oil Papillary muscle Atrial muscle Repolarization
☻ Effect of Alpha Tocopherol on the Growth Plate in Albino rats-PDF file
Abhaya, A., Khatri, K., Pradhan, S. and Prakash, R.
Department of Anatomy, University College of Medical Sciences & G.T.B. Hospital, Shahdra, Delhi. INDIA.
J. Anat. Soc. India 52(1) 58-63 (2003)
Abstract. — Alpha tocopherol is the most biologically active stereoisomer of vitamin E and recent investigations suggest that vitamin E is important for bone mineralization and normal endochondral ossification. Thirty Albino rats (8-20 days) included in the study were divided into three groups. Experimental group C was given tocopherol (90mg/Kg body weight) daily, orally for 12 days. Group B was treated with equal amount of arachis oil (vehicle) daily for 12 days while group A animals were kept untreated. On 20th day animals were sacrificed and 6m thick longitudinal sections of decalcified radius were stained for light microscopy. Growth plate was differentiated into resting, proliferative, hypertrophic zone I and hypertrophic zone II. Morphometric observations were recorded at the central and lateral regions of the growth plate. The height (vertical thickness) of growth plate showed a statistically significant increase in the central region (P = 0.000). The zonal thickness of hypertrophic zone I also increased in central region (P = 0.004) while the zonal thickness of hypertrophic zone II showed a significant increase in the lateral region (P=0.040). Cell population of hypertrophic zone I increased significantly in central (P=0.000) and lateral region (P =0.002) while the cell population of hypertrophic zone II decreased significantly in central (P=0.000) as well as lateral region (P=0.011). The number of cell columns decreased significantly (P= 0.028) in hypertrophic zone II. Intense matrix metachromasia was seen in vitamin E treated animals. These results suggest that vitamin E promotes mineral apposition, multiplication and maturation of chondrocytes and thereby may enhance longitudinal bone growth.
Key words : Alpha Tocopherol, Growth Plate, Radius, Rat
☻ EFFECT OF VITAMIN E ON THEIMPAIRED GASTROINTESTINALACTIVITY OF STREPTOZOTOCIN-INDUCED DIABETIC RATS-PDF file
S. BIJENDER*, D. HARISH*, S. RISHI**,B.M. PATIL***
*Department of Pharmaceutical Sciences, M.D.University, Rohtak-124 001.
**B.M.N. Institute of Pharmaceutical Sciences andResearch, Asthal Bohar, Rohtak-124 001.
***Department of Pharmaceutical Sciences,K.L.E's College of Pharmacy, Belgaum-590 010
Indian Journal of Pharmacology 2003; 35: 186-187
☻ Molecular Basis of Vitamin E Action-PDF file
TOCOTRIENOL MODULATES 12-LIPOXYGENASE, A KEY MEDIATOR OF GLUTAMATE-INDUCED NEURODEGENERATION*□S
Savita Khanna‡, Sashwati Roy‡, Hoon Ryu§, Praveen Bahadduri¶, Peter W. Swaan¶,
Rajiv R. Ratan§, and Chandan K. Sen‡
From the ‡Laboratory of Molecular Medicine, Department of Surgery, and the ¶Bioinformatics and Computational Biology
Core Laboratory, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center,
Columbus, Ohio 43210 and the §Department of Neurology, Harvard Medical School, and the Beth Israel Deaconess
Medical Center, Boston, Massachusetts 02115
THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 278, No. 44, Issue of October 31, pp. 43508–43515, 2003
Vitamin E is a generic term for tocopherols and tocotrienols. This work is based on our striking evidence that, in neuronal cells, nanomolar concentrations of α-tocotrienol, but not α-tocopherol, block glutamate-induced death by suppressing early activation of c-Src kinase (Sen, C. K., Khanna, S., Roy, S., and Packer, L. (2000) J. Biol. Chem. 275, 13049–13055). This study on HT4 and immature primary cortical neurons suggests a central role of 12-lipoxygenase (12-LOX) in executing glutamate-induced neurodegeneration. BL15, an inhibitor of 12-LOX, prevented glutamate-induced neurotoxicity. Moreover, neurons isolated from 12-LOX-deficient mice were observed to be resistant to glutamate-induced death. In the presence of nanomolar α-tocotrienol, neurons were resistant to glutamate-, homocysteine-, and L-buthionine sulfoximine-induced toxicity. Long-term time-lapse imaging studies revealed that neurons and their axo-dendritic network are fairly motile under standard culture conditions. Such motility was arrested in response to glutamate challenge. Tocotrienol- treated primary neurons maintained healthy growth and motility even in the presence of excess glutamate. The study of 12-LOX activity and metabolism revealed that this key mediator of glutamate-induced neurodegeneration is subject to control by the nutrient α-tocotrienol. In silico docking studies indicated that α-tocotrienol may hinder the access of arachidonic acid to the catalytic site of 12-LOX by binding to the opening of a solvent cavity close to the active site. These findings lend further support to α-tocotrienol as a potent neuroprotective form of vitamin E.
☻ pH-dependent translocation of α-tocopherol transfer protein (α-TTP) between hepatic cytosol and late endosomes-PDF file
Masakuni Horiguchi1,2, Makoto Arita1, Daisy E. Kaempf-Rotzoll1, Masafumi Tsujimoto2,Keizo Inoue3 and Hiroyuki Arai1,*
1 Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan
2 Laboratory of Cellular Biochemistry, RIKEN (the Institute of Physical and Chemical Research), Saitama, Japan
3 Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan
Abstract
Background: α-Tocopherol transfer protein (α-TTP), a member of the Sec14 protein family, plays an important role in transporting α-tocopherol, a major lipidsoluble anti-oxidant, in the cytosolic compartment of hepatocytes and is known as a product of the causative gene for familial isolated vitamin E deficiency. It has been shown that the secretion of hepatocyte α-tocopherol taken up with plasma lipoproteins is facilitated by α-TTP. To explore the mechanism of α-TTP mediated α-tocopherol secretion, we investigated drugs which may affect this secretion.
Results: We found that, in a hepatocyte cell culture system, intracellular α-tocopherol transport is impaired by chloroquine, an agent known for its function of elevating the pH in acidic compartments. Under chloroquine treatment, the diffuse cytosolic distribution of α-TTP changes to a punctate pattern. Doublestaining experiments with endocytosis markers revealed that α-TTP accumulates transiently on the cytoplasmic surface of late endosomal membranes. This phenomenon is specific for hepatoma cell lines or primarily cultured hepatocytes. Other members of the Sec14 family, such as cellular retinaldehyde-binding protein (CRALBP) and supernatant protein factor (SPF), do not show this accumulation. Furthermore, we elucidate that the obligatory amino acid sequence for this function is located between amino acids 21 and 50, upstream of the N-terminal end of the lipidbinding domain.
Conclusion: We hypothesize that a liver-specific target molecule for α-TTP exists on the late endosomal membrane surface. This transient binding may explain the mechanism of how α-tocopherol is transferred from late endosomes to cytosolic α-TTP.
☻ The Effects of Fenthion on Lipid Peroxidation and Some Liver Enzymes: The Possible Protective Role of Vitamins E and C-PDF file
Ürfan ALTUNTAÞ NamÝk DELÜBAÞ
Department of Biochemistry and Clinical Biochemistry, Faculty of Medicine, S.leyman Demirel University, Isparta – Turkey
Turk J Med Sci 32 (2002) 293-297
Abstract: The effects of fenthion on the serum activities of cholinesterase (ChE), enzymes concerning liver damage and lipid peroxidation (LPO), and the ameliorating effects of a combination of vitamins E and C against fenthion toxicity were investigated. The results of the in vivo experiment showed that fenthion caused a significant increase in LPO and the activities of aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) and lactate dehydrogenase (LDH), and a significant decrease in the activities of ChE and alanine aminotransferase (ALT). In addition, treatment with a combination of vitamins E and C led to a significant decrease in LPO and AST activity. In the in vitro experiment, the activity of ChE and ALT were inhibited by fenthion. From these results, it can be concluded that fenthion caused liver damage, and LPO may be one of the molecular mechanisms involved in fenthion-induced toxicity. Vitamins E and C can reduce LPO caused by fenthion.
Key Words: Fenthion, liver, lipid peroxidation, vitamin E, vitamin C
☻ α-TOCOPHEROL IN MICE ILEUM EXPOSED TO GAMMA RADIATION: PROTECTION AGAINST APOPTOSIS-PDF file
1França, J.P.; 1Moraes A.A.F.S.; 2Trindade, E.S.; 3Segreto, H.R.C.; 1Paredes-Gamero, E.J.; 1Oshiro, M.E. M.; 1Nunes, R.O.; Aguilar, M.O.; 3*Pedroso, M.Z.; 4Silva, M.R.R.; 5Egami, M.I.; 2Nader, H.B. and 1Ferreira, A.T.
Departments of 1Biophysics; 2Biochemistry; 3Medicine; 4Pathology Anatomy and 5Morphology. UNIFESP/EPM, 04041-990, São Paulo- SP-Brazil.
*Centro Universitário São Camilo, 04263-200, São Paulo- SP - Brazil
Ionizing radiation is largely used in the research, in the diagnosis and treatment of diseases, mainly in neoplasias. The syndrome of radiation leads to diarrhea, hemorrhage, increase of intracranial pressure and it mainly occurs by alterations and death of intestine, bone marrow and neuronal cells. Further studies are necessary in order to understand its interactions at cellular level and mechanism the radioprotection by α-tocoferol in cells intestinal [1]. The radiation interacts with lipids and proteins of the cell. The radioinduced alterations in the cellular membrane components have important consequences for the cellular functions [2-3].
☻ The selenium and vitamin E cancer prevention trial-PDF file
Eric A. Kleina,*, Ian M. Thompsonb, Scott M. Lippmanc, Phyllis J. Goodmand, Demetrius Albanese, Philip R. Taylore, Charles Coltmanf
a Section of Urologic Oncology, Department of Urology, Cleveland Clinic Foundation, Cleveland, OH, USA b Division of Urology, University of Texas Health Sciences Center, San Antonio, TX, USA c Department of Clinical Cancer Prevention, M.D. Anderson Cancer Center, Houston, TX, USA d Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA e Cancer Prevention Studies Branch, Division of Clinical Sciences, National Cancer Institute, Washington, DC, USA f Southwest Oncology Group, San Antonio, TX, USA
Abstract
Purpose: Growing evidence suggests that both selenium and vitamin E may reduce the risk of prostate cancer. SELECT is a randomized, prospective, double-blind study designed to determine if selenium and vitamin E can reduce the risk of prostate cancer among healthy men. Materials and methods: The preclinical and epidemiologic evidence regarding chemoprevention with selenium and vitamin E were reviewed. Secondary analyses from randomized trials of both agents were included in the analysis. Data from these analyses as well as evidence from the Prostate Cancer Prevention Trial were used to develop the schema of SELECT. Results: Preclinical, epidemiologic, and Phase III data suggest that both selenium and vitamin E have potential efficacy in prostate cancer prevention. The experience of the Prostate Cancer Prevention Trial and the rapid accrual of SELECT during its first year demonstrate the interest and dedication of healthy men to long-term studies of cancer prevention. A total of 32,400 men are planned to be randomized in SELECT. Conclusions: SELECT is the second large-scale study of chemoprevention for prostate cancer. Enrollment began in 2001 with final results anticipated in 2013. © 2003 Elsevier Science Inc. All rights reserved.
Keywords: Prostate cancer; Chemoprevention; Selenium; Vitamin E
☻ Alpha-Tocopherol Supplementation in Healthy Individuals Reduces Low-Density Lipoprotein Oxidation but Not Atherosclerosis The Vitamin E Atherosclerosis Prevention Study (VEAPS)-PDF file
Howard N. Hodis, MD; Wendy J. Mack et al
Circulation September 17, 2002;106:1453-1459
Background—Epidemiological studies have demonstrated an inverse relationship between vitamin E intake and cardiovascular disease (CVD) risk. In contrast, randomized controlled trials have reported conflicting results as to whether vitamin E supplementation reduces atherosclerosis progression and CVD events. Methods and Results—The study population consisted of men and women ≥40 years old with an LDL cholesterol level ≥3.37 mmol/L (130 mg/dL) and no clinical signs or symptoms of CVD. Eligible participants were randomized to DL-α-tocopherol 400 IU per day or placebo and followed every 3 months for an average of 3 years. The primary trial end point was the rate of change in the common carotid artery far-wall intima-media thickness (IMT) assessed by computer image–processed B-mode ultrasonograms. A mixed effects model using all determinations of IMT was used to test the hypothesis of treatment differences in IMT change rates. Compared with placebo, α-tocopherol supplementation significantly raised plasma vitamin E levels (P,0.0001), reduced circulating oxidized LDL (P50.03), and reduced LDL oxidative susceptibility (P,0.01). However, vitamin E supplementation did not reduce the progression of IMT over a 3-year period compared with subjects randomized to placebo. Conclusions—The results are consistent with previous randomized controlled trials and extend the null results of vitamin E supplementation to the progression of IMT in healthy men and women at low risk for CVD.
Key Words: coronary disease; atherosclerosis; antioxidants; trials
☻ The Selenium and Vitamin E Cancer Prevention Trial (SELECT)-PDF file
SOUTHWEST ONCOLOGY GROUP STATISTICAL CENTER JULY 2002
Overview
The Selenium and Vitamin E Cancer Prevention Trial (SELECT) (S0000) is a Phase III, randomized, double blind, placebo-controlled trial to prevent prostate cancer. SELECT will accrue 32,400 healthy men, ages 55 years and older (African American men ages 50 years and older). It is planned that 20% (6,480) of the study participants will be African American. The efficacy of selenium and vitamin E, as single agents and in combination, on reduction of prostate cancer incidence, will be tested in a statistically highly powered 2 x 2 factorial trial design. The total study period is 14 years, including 1 year pre-study for ramp-up to accrual (completed), 5 years for accrual, 7 to 12 years of treatment, and 1 year post-study for analyses and publication of results. Participants will be followed twice per
year (four times in the first year after randomization) to monitor general health, prostate health, and adherence to the study supplements.
☻ Tocopherol (vitamin E) content in invasive browse species on underutilized Appalachian farmland-PDF file
By Gabriel Wilmoth Thesis submitted to the faculty of the Virginia Polytechnic Institute and State University in partial fulfillment of the requirements for the degree of Master of Science in Biochemistry J. L. Hess, Chair J. G. Foster E. M. Gregory A. O. Abaye May, 2000 Blacksburg, VA
(Abstract)
The tocopherol (Vitamin E) content of forage from three invasive shrub species was measured to assess the value of the shrubs as a source of vitamin E for goats browsing on overgrown Appalachian pastures. Plant leaf clusters were collected from multiflora rose (Rosa multiflora Thunb.), autumn olive (Elaeagnus umbellata Thunb.), and Morrow’s honeysuckle (Lonicera morowii Gray) in replicated plots at a site in southern West Virginia during the 1999 growing season. Alpha-, beta-, gamma-, and delta-tocopherol were extracted with hexane, separated by high performance liquid chromatography on a normal-phase diol column, and quantified. Significant differences (P<0.001) in concentration were found among species for all forms of tocopherol. Alpha-tocopherol predominated, accounting for more than 90% of the total tocopherols in all three species. Alpha-tocopherol levels increased in all species with maturity; however, the magnitude of the increase was not the same in all species. At the end of the growing season, autumn olive had the highest levels of alpha-tocopherol (1270 ± 55 ppm dry matter [DM]), followed by Morrow’s honeysuckle (840 ± 55 ppm DM), and multiflora rose (610 ± 55 ppm DM). Goats grazing on mature browse may obtain adequate intake of vitamin E. High nutritive value and/or low concentrations of antiquality factors may not coincide with the high levels of vitamin E found in mature tissue, and the actual vitamin E intake will depend on the feeding behavior of the goat.
☻ Cardiovascular Aging Is Associated With Vitamin E Increase-PDF file
Bernd van der Loo, MD; Ralf Labugger, MSc; Claude P. Aebischer, PhD; Jeremy N. Skepper, PhD; Markus Bachschmid, MSc; Volker Spitzer, PhD; Juliane Kilo, MD; Lukas Altwegg, MD; Volker Ullrich, PhD; Thomas F. Lüscher, MD, FRC
Circulation April 9, 2002(Circulation. 2002;105:1635-1638.)
Background: Aging is an independent risk factor for the development of cardiovascular disease. Therefore, therapies to delay vascular aging may have enormous medical consequences. In this context, vitamin E is of particular interest, mainly because of its antioxidative properties. Methods and Results: In 3-year-old rats, which are not susceptible to atherosclerosis, vitamin E levels, as measured by reversed-phase high-performance liquid chromatography, were markedly increased both in plasma and in major organs (P,0.01 to P,0.0001). The highest increase (at least 70-fold) was found in the aortic wall. Conclusions: This unexpected accumulation of vitamin E appears to be a compensatory mechanism that attempts to counterbalance age-associated oxidative stress and that may represent a self-regulatory protective adaptation.
Key Words: aging; cardiovascular diseases; vitamin E; antioxidative defense
☻ Comparing β-Carotene, Vitamin E and Nitric Oxide as Membrane Antioxidants-PDF file
Freya Q. Schafer*, Hong P. Wang, Eric E. Kelley,Kate L. Cueno, Sean M. Martin and Garry R. Buettner
Biol. Chem., Vol. 383, pp. 671 – 681, March /April 2002
Singlet oxygen initiates lipid peroxidation via a nonfree radical mechanism by reacting directly with unsaturated lipids to form lipid hydroperoxides (LOOHs). These LOOHs can initiate free radical chain reactions leading to membrane leakage and cell death. Here we compare the ability and mechanism by which three small-molecule membrane antioxidants (β-carotene, β-tocopherol and nitric oxide) inhibit lipid peroxidation in membranes. We demonstrate that β-carotene provides protection against singlet oxygen-mediated lipid peroxidation, but does not slow free radical-mediated lipid peroxidation. β-Tocopherol does not protect cells from singlet oxygen, but does inhibit free radical formation in cell membranes. Nitric oxide provides no direct protection against singlet oxygen exposure, but is an exceptional chain-breaking antioxidant as evident from its ability to blunt oxygen consumption during free radical-mediated lipid peroxidation. These three small molecule antioxidants appear to have complementary mechanisms for the protection of cell membranes from detrimental oxidations.
Key words: Antioxidants; β-Carotene; Free radicals; Lipid peroxidation; Nitric oxide; Singlet oxygen; Tocopherol; Vitamin E.
☻ Oxidized lipid accumulates in the presence of α-tocopherol in atherosclerosis-PDF file
Joanne M. UPSTON*, Andrew C. TERENTIS*, Kathryn MORRIS*, John F. KEANEY, JR. and Roland STOCKER*1
*Biochemistry Group, The Heart Research Institute, 145 Missenden Road, Camperdown, Sydney, NSW, 2050, Australia, and .Whitaker Cardiovascular Institute,Evans Memorial Department of Medicine, Boston University Medical Center, Boston, MA 02 118, U.S.A.
Biochem. J. (2002) 363, 753-760
Oxidative modification of low-density lipoproteins in the arterial wall is a key feature of atherogenesis and widely believed to cause and/or accelerate lesion development. Linked to this is the expectation that vascular antioxidants are depleted during oxidation in .i.o. However, whether α-tocopherol (vitamin E), an important lipid-soluble antioxidant, is depleted early in atherogenesis and can prevent lipid peroxidation in .i.o is unresolved. To address this we examined the content of specific con-figurational isomers (cis/trans) of lipid hydro(pero)xides in lesions, which represent the major non-enzymic oxidation products, as formation and accumulation of cis/trans isomers is influenced by α-tocopherol in studies in .itro. Concordant with our previous findings that large amounts of oxidized lipid coexist with relatively normal α-tocopherol levels in human lesions, we now show that cis/trans isomers predominate over other products in human carotid and aortic lesions and in lesion lipoproteins. Further, dietary vitamin E supplementation of rabbits after arterial injury significantly increases both the aortic levels of α-tocopherol and the overall content of cis/trans isomers. These data are fully consistent with α-tocopherol acting as a hydrogen donor during lipid oxidation in .i.o and suggest that α-tocopherol does not prevent lipoprotein lipid oxidation in the diseased vessel wall.
Key words: hydroxylinoleate, lipid oxidation, lipoprotein, stereo isomer, vitamin E.
☻ Vitamin E in cardiovascular disease: has the die been cast?-PDF file
Khalid Yusoff FRCPE, FRCP, FACC
Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
Asia Pacific J Clin Nutr (2002) 11(Suppl): S443–S447
Cardiovascular disease, in particular coronary artery disease (CAD), remains the most important cause of morbidity and mortality in developed countries and, in the near future, more so in the developing world. Atherosclerotic plaque formation is the underlying basis for CAD. Growth of the plaque leads to coronary stenosis, causing a progressive decrease in blood flow that results in angina pectoris. Acute myocardial infarction and unstable angina were recently recognised as related to plaque rupture, not progressive coronary stenosis. Acute thrombus formation causes an abrupt coronary occlusion. The characteristics of the fibrin cap, contents of the plaque, rheological factors and active inflammation within the plaque contribute to plaque rupture. Oxidative processes are important in plaque formation. Oxidized low density lipoproteins (LDL) but not unoxidized LDL is engulfed by resident intimal macrophages, transforming them into foam cells which develop into fatty streaks, the precursors of the atherosclerotic plaque. Inflammation is important both in plaque formation and rupture. Animal studies have shown that antioxidants reduce plaque formation and lead to plaque stabilization. In humans, high intakes of antioxidants are associated with lower incidence of CAD, despite high serum cholesterol levels. This observation suggests a role for inflammation in CAD and that reducing inflammation using antioxidants may ameliorate these processes. Men and women with high intakes of vitamin E were found to have less CAD. Vitamin E supplementation was associated with a significant reduction in myocardial infarction and cardiovascular events in the incidence of recurrent myocardial infarction. In the hierarchy of evidence in evidence-based medicine, data from large placebo-controlled clinical trials is considered necessary. Results from various mega-trials have not shown benefits (nor adverse effects) conferred by vitamin E supplementation, suggesting that vitamin E has no role in the treatment of CAD. These results do not seem to confirm, at the clinical level, the effect of antioxidants against active inflammation during plaque rupture. However, a closer examination of these studies showed a number of limitations, rendering them inconclusive in addressing the role of vitamin E in CAD prevention and treatment. Further studies that specifically address the issue of vitamin E in the pathogenesis of atherosclerosis and in the treatment of CAD need be performed. These studies should use the more potent antioxidant property of α- tocopherol vitamin E.
Key words: Antioxidants, cardiovascular disease, vitamin E.