Dietary antioxidants and risk of Parkinson’s disease in two population-based cohorts.

Yang F, Wolk A, Håkansson N, Pedersen NL, Wirdefeldt K

Mov Disord. 2017 Nov;32(11):1631-1636. doi: 10.1002/mds.27120. Epub 2017 Sep 7.

Abstract

BACKGROUND:

A neuroprotective effect of dietary antioxidants on Parkinson’s disease (PD) risk has been suggested, but epidemiological evidence is limited.

OBJECTIVES:

To examine the associations between intake of dietary antioxidant vitamins and total antioxidant capacity and risk of PD.

METHODS:

We prospectively assessed the relationships of dietary antioxidant vitamins C and E, ß-carotene, and total antioxidant capacity with PD risk in two population-based cohorts (38,937 women and 45,837 men).

RESULTS:

During a mean 14.9-year follow-up period, 1,329 PD cases were identified. Dietary intake of ß-carotene was associated with a lower risk of PD (hazard ratio: 0.86; 95% confidence interval: 0.78-0.95; Ptrend  < 0.01 for women and hazard ratio: 0.91; 95% confidence interval: 0.84-0.99; Ptrend  = 0.05 for men). An inverse association between dietary vitamin E and PD risk was found in women (hazard ratio: 0.87; 95% confidence interval: 0.79-0.96; Ptrend  = 0.02). Dietary intake of vitamin C was inversely associated with PD risk in women at borderline significance (hazard ratio: 0.91; 95% confidence interval: 0.83-1.00; Ptrend  = 0.04). There was no association between dietary total antioxidant capacity and PD risk in either women (hazard ratio: 0.93; 95% confidence interval: 0.84-1.02; Ptrend  = 0.35) or men (hazard ratio: 1.00; 95% confidence interval: 0.93-1.07; Ptrend  = 0.97).

CONCLUSION:

Intake of dietary vitamin E and ß-carotene was associated with a lower risk of PD.

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Effects of phoxim-induced hepatotoxicity on SD rats and the protection of vitamin E.

Zhang J, Song W, Sun Y, Shan A

Environ Sci Pollut Res Int. 2017 Nov;24(32):24916-24927. doi: 10.1007/s11356-017-0104-1.

Abstract

Currently, public pay more attention to the adverse effect of organophosphate pesticides on human and animal health and on the environment in developing nations. Vitamin E may protect the hepatocyte and increase the function of liver. The study was to investigate the effects of phoxim-induced hepatotoxicity on Sprague Dawley (SD) rats and the protection of vitamin E. SD rats received by gavage 180 mg kg-1 (per body weight) of phoxim, 200 mg kg-1 (per body weight) of vitamin E, and phoxim + vitamin E. The results showed that exposure to phoxim elevated liver coefficient; glutamyl transpeptidase (GGT), aspartate aminotransferase, alkaline phosphatase, total bilirubin, total bile acid, and alanine aminotransferase in the serum; ROS in the liver; and the expression of p53, Bax, CYP2E1, ROS, caspase-9, caspase-8, and caspase-3, while phoxim caused a reduction of total protein, albumin, and cholinesterase in the serum; acetylcholinesterase, total antioxidant capacity, glutathione peroxidase, and glutathione in the liver; and the expression of Bcl-2. Vitamin Emodified the phoxim-induced hepatotoxicity by reducing the GGT in the serum, malondialdehyde in the liver, and the expression of CYP2E1 significantly. There were no significant changes of globulin in the serum, the activity of catalase in the liver, as well as expression levels of Fas and Bad in the liver. Overall, subacute exposure to phoxim induced hepatic injury, oxidative stress damage, and cell apoptosis. Vitamin Emodified phoxim-induced hepatotoxicity slightly. And, vitamin E minimized oxidative stress damage and ultrastructural changes in rat hepatocytes notably.

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Vitamin E treatment decreases muscle injury in mdx mice.

Mâncio RD, Hermes TA, Macedo AB, Mizobuti DS, Valduga AH, Rupcic IF, Minatel E

Nutrition. 2017 Nov - Dec;43-44:39-46. doi: 10.1016/j.nut.2017.07.003.

Abstract

OBJECTIVE:

Oxidative stress, in addition to the absence of the dystrophin protein, has been considered an important regulator of Duchenne muscular dystrophy (DMD). Vitamin E presents an important role as a potent antioxidant and in preserving the integrity of the cell membrane. In this study, we evaluated the effects of vitamin E therapy on some physiological pathways that can contribute to muscle injury in the diaphragm muscle of mdx mice (the experimental model of DMD) such as CK levels, inflammatory response, oxidative stress, and the enzymatic antioxidant system.

METHODS:

Mdx mice (14 d old) received 40 mg vitamin E/kg daily by oral gavage for 14 d, followed by the removal of the diaphragm muscle. Control mdx mice and C57BL/10 mice received saline only for the same period and were used as controls.

RESULTS:

Vitamin E reduced the muscle fiber damage, oxidative stress, and inflammation process in the diaphragm muscle of mdx mice.

CONCLUSIONS:

Vitamin E improves skeletal muscle injury in mdx mice, promoting membrane repair and exhibiting antioxidant and antiinflammatory effects. These vitamin E effects suggest that this antioxidant therapy may be a relevant approach for dystrophinopathies.

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Antioxidant defense system in familial hypercholesterolemia and the effects of lipoprotein apheresis.

Blaha V, Blaha M, Solichová D, Krčmová LK, Lánská M, Havel E, Vyroubal P, Zadák Z, Žák P, Sobotka L

Atheroscler Suppl. 2017 Nov;30:159-165. doi: 10.1016/j.atherosclerosissup.2017.05.002.

Abstract

Oxidative stress is thought to play an important role in the pathogenesis of disorders associated with atherosclerosis. Alpha-tocopherol is considered to be an effective lipophilic antioxidant, which protects lipid membranes against peroxidation and thus prevents cell damage by reaction with free radicals. However, measurement of alpha-tocopherol concentration in serum does not reflect the content of α-tocopherol in membranes whereas erythrocyte alpha-tocopherol may be good indicator of antioxidative status. Therefore a simple isocratic reversed phase HPLC method has been developed and validated for the determination of alpha-tocopherol in human erythrocytes in a clinical setting. The content of alpha-tocopherol in human erythrocyte membrane and lipoperoxidation were studied in patients with severe hypercholesterolemia treated by lipoprotein apheresis. The group of hypercholesterolemic patients (n = 14) treated by lipoprotein apheresis was compared to healthy adult normolipidemic controls. After lipoprotein apheresis, the content of in membrane alpha-tocopherol did not change significantly despite decreased tocopherol in serum and lipoprotein fractions. We observed significantly decreased lipoperoxidation as revealed by serum TBARS, representing end products of lipid peroxidation, which increased from third day afterwards and remained significantly higher in comparison to controls until the next LDL-apheresis. We conclude that aggressive lipid lowering procedure with lipoprotein apheresis was associated with favorable transient decrease of lipoperoxidation. Simultaneously the cell membrane bound antioxidative defense mechanisms as reflected by the content of alpha-tocopherol in human erythrocyte membrane where not depressed in spite of its decreased plasma lipid carrier. Another variables involved remain to be investigated.

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Advances in Genetic Improvement for Tocotrienol Production: A Review.

Babura SR, Abdullah SNA, Khaza Ai H

J Nutr Sci Vitaminol (Tokyo). 2017;63(4):215-221. doi: 10.3177/jnsv.63.215.

Abstract

Tocotrienols are forms of vitamin E that are present in several important food crops. Compared to tocopherols, less research has been conducted on these compounds because of their low bioavailability and distribution in plant tissues. Both tocotrienols and tocopherols are known for their antioxidant and anticancer activities, which are beneficial for both humans and animals. Moreover, tocotrienols possess certain properties which are not found in tocopherols, such as neuroprotective and cholesterol-lowering activities. The contents of tocotrienolsin plants vary. Tocotrienols constitute more than 70% and tocopherols less than 30% of the total vitamin E content in palm oil, which is the best source of vitamin E. Accumulation of tocotrienols also occurs in non-photosynthetic tissues, such as the seeds, fruits and latex of some monocotyledonous and dicotyledonous plant species. The use of biotechnological techniques to increase the tocotrienol content in plants, their biological functions, and benefits to human health are discussed in this review.

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δ-Tocopherol inhibits the development of prostate adenocarcinoma in prostate specific Pten-/- mice.

Wang H, Yang X, Liu A, Wang G, Bosland MC, Yang CS

Carcinogenesis. 2017 Nov 7. doi: 10.1093/carcin/bgx128.

Abstract

The PTEN/PI3K/AKT axis plays a critical role in regulating cell growth, differentiation and survival. Activation of this signaling pathway is frequently found in human cancers. Our previous studies demonstrated that δ-tocopherol (δ-T) attenuates the activation of AKT by growth factor in prostate cancer cell lines, leading to inhibition of proliferation and induction of apoptosis. Herein, we investigated whether δ-T inhibits the development of prostate adenocarcinoma in prostate-specific Pten-/- (Ptenp-/-) mice in which the activation of AKT is the major driving force for tumorigenesis. By feeding Ptenp-/- mice with AIN93M or 0.2% δ-T supplemented diet starting at the age of 6 or 12 weeks, we found that δ-T treatment reduced prostate adenocarcinoma multiplicity at the age of 40 weeks by 53.3% and 42.7%, respectively. Immunohistochemical analysis demonstrated that the phosphorylation of AKT(T308) was reduced in the prostate of the mice administered the δ-T diet. Consistently, proliferation was reduced and apoptosis was increased in prostate lesions of mice on the δ-T diet. Oxidative stress, as determined by immunohistochemical staining of 8-OH-dG, was not altered during prostate tumorigenesis, nor was it affected by administration of δ-T. In contrast, α-tocopherol (δ-T) at 0.2% in the diet did not affect prostate adenocarcinoma multiplicity in the Ptenp-/- mice. This finding is consistent with data from our previous study that δ-T, but not δ-T, inhibits the activation of AKT and the growth of prostate cancer cells. Together, these results demonstrate that δ-T inhibits the development of prostate adenocarcinoma in Ptenp-/- mice, mainly through inhibition of AKT activation.

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Hemin- and myoglobin-catalyzed reaction of 1-palmitoyl-2-linoleoyl-3-sn-phosphatidylcholine 13-hydroperoxide with γ-tocopherol in micelles and liposomes.

Yamauchi R, Kinoshita T, Hasegawa Y, Iwamoto S

Chem Phys Lipids. 2017 Nov 7;209:37-44. doi: 10.1016/j.chemphyslip.2017.11.005.

Abstract

The secondary process of lipid peroxidation proceeds by the free radical reaction to produce some toxic aldehydes. Since γ-tocopherol (γ-TH), one of the major forms of vitamin E in some vegetable oils, acts as a free radical scavenger, γ-TH may suppress the formation of such aldehydes. This study reports the effect and reaction products of γ-TH on the hemin- or myoglobin-catalyzed decomposition of 1-palmitoyl-2-linoleoyl-3-sn-phosphatidylcholine 13-hydroperoxide (PLPC-OOH) in micelles and liposomes. γ-TH and PLPC-OOH in micelles were reacted in the presence of hemin, and the reaction products were characterized as 1-palmitoyl-2-[(8a-dioxy-γ-tocopherone)-12,13-epoxyoctadecenoyl]-3-sn-phosphatidylcholines (γT-OO-epoxyPLPC), 1-palmitoyl-2-[(γ-tocopheroxy)-12,13-epoxyoctadecenoyl]-3-sn-phosphatidylcholines (γT-epoxyPLPC), and the adducts of γ-TH dimer with PLPC-OOH derived epoxyperoxyl and epoxyalkyl radicals (γTD-OO-epoxyPLPC and γTD-epoxyPLPC). The hemin- and myoglobin-catalyzed decomposition of PLPC-OOH in micelles produced hexanal and 4-hydroxy-2-nonenal as the major aldehydic products. γ-TH suppressed the formation of these aldehydes as the same level as α-TH did, and γ-tocopherylquinone, tocored, γ-TH dimers, and the addition products (γT-OO-epoxyPLPC, γT-epoxyPLPC, γTD-OO-epoxyPLPC, and γTD-epoxyPLPC) were formed during the reaction. In liposomes, hexanal was detected as the major aldehyde and its suppression by γ-TH was less effective than that by α-TH. The results indicate that γ-TH may suppress the formation of aldehydes by trapping the epoxyperoxyl and epoxyalkyl radicals derived from PLPC-OOH although its ability is weak in liposomal systems.

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A green multicomponent synthesis of tocopherol analogues with antiproliferative activities.

Ingold M, Dapueto R, Victoria S, Galliusi G, Batthyàny C, Bollati-Fogolín M, Tejedor D, García-Tellado F, Padrón JM, Porcal W, López GV

Eur J Med Chem. 2017 Nov 3. pii: S0223-5234(17)30888-7. doi: 10.1016/j.ejmech.2017.11.003.

Abstract

A one-pot efficient, practical and eco-friendly synthesis of tocopherol analogues has been developed using water or solvent free conditions via Passerini and Ugi multicomponent reactions. These reactions can be optimized using microwave irradiation or ultrasound as the energy source. Accordingly, a small library of 30 compounds was prepared for biological tests. The evaluation of the antiproliferative activity in the human solid tumor cell lines A549 (lung), HBL-100 (breast), HeLa (cervix), SW1573 (lung), T-47D (breast), and WiDr (colon) provided lead compounds with GI50 values between 1 and 5 μM. A structure-activity relationship is also discussed. One of the studied compounds comes up as a future candidate for the development of potent tocopherol-mimetic therapeutic agents for cancer.

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Epidermal E-Cadherin Dependent β-Catenin Pathway Is Phytochemical Inducible and Accelerates Anagen Hair Cycling.

Ahmed NS, Ghatak S, El Masry MS, Gnyawali SC, Roy S, Amer M, Everts H, Sen CK, Khanna S

Mol Ther. 2017 Nov 1;25(11):2502-2512. doi: 10.1016/j.ymthe.2017.07.010. Epub 2017 Jul 20.

Abstract

Unlike the epidermis, which regenerates continually, hair follicles anchored in the subcutis periodically regenerate by spontaneous repetitive cycles of growth (anagen), degeneration (catagen), and rest (telogen). The loss of hair follicles in response to injuries or pathologies such as alopecia endangers certain inherent functions of the skin. Thus, it is of interest to understand mechanisms underlying follicular regeneration in adults. In this work, a phytochemical rich in the natural vitamin E tocotrienol (TRF) served as a productive tool to unveil a novel epidermal pathway of hair follicular regeneration. Topical TRF application markedly induced epidermal hair follicle development akin to that during fetal skin development. This was observed in the skin of healthy as well as diabetic mice, which are known to be resistant to anagen hair cycling. TRF suppressed epidermal E-cadherin followed by 4-fold induction of β-catenin and its nuclear translocation. Nuclear β-catenin interacted with Tcf3. Such sequestration of Tcf3 from its otherwise known function to repress pluripotent factors induced the plasticity factors Oct4, Sox9, Klf4, c-Myc, and Nanog. Pharmacological inhibition of β-catenin arrested anagen hair cycling by TRF. This work reports epidermal E-cadherin/β-catenin as a novel pathway capable of inducing developmental folliculogenesis in the adult skin.

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Palm vitamin E reduces locomotor dysfunction and morphological changes induced by spinal cord injury and protects against oxidative damage.

Zadeh-Ardabili PM, Rad SK, Rad SK, Khazaài H, Sanusi J, Zadeh MH

Sci Rep. 2017 Oct 30;7(1):14365. doi: 10.1038/s41598-017-14765-3.

Abstract

Spinal cord injury (SCI) occurs following different types of crushes. External and internal outcomes of SCI are including paralysis, cavity, and cyst formation. Effects of dietary derived antioxidants, such as palm vitamin E on central nervous system (CNS) encourage researchers to focus on the potential therapeutic benefits of antioxidant supplements. In the present study, experiments were carried out to evaluate the neuro-protective effect of the palm vitamin E on locomotor function and morphological damages induced SCI. Seventy-two male rats (Sprague-Dawley) were randomly divided into four groups: sham (laminectomy); control (supplemented with the palm vitamin E at a dose of 100 mg/kg/day); untreated-SCI (partial crush, 30-33% for 20 sec); treated-SCI (partial crush, 30-33% for 20 sec supplemented with the palm vitamin E at a dose of 100 mg/kg/day). The treatment with the palm vitamin E significantly improved the hind limb locomotor function, reduced the histopathological changes and the morphological damage in the spinal cord. Also, the palm vitamin E indicated a statistically significant decrease in the oxidative damage indicators, malondialdehyde (MDA) level and glutathione peroxidase (GPx) activity in the treated-SCI compared to the untreated-SCI.

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