Synergistic protective effect of FTY720 and vitamin E against simulated cerebral ischemia in vitro.

Pang X, Hou X

Mol Med Rep. 2017 May 11. doi: 10.3892/mmr.2017.6572. [Epub ahead of print]

Abstract

The purpose of the present study was to explore the combination effect of FTY720 and vitamin E on cerebral ischemia. Astrocytes were isolated from newborn Sprague‑Dawley rats and were subjected to FTY720, vitamin E, or combination of the two. The astrocyte cultures were then exposed to oxygen‑glucose deprivation (OGD) to simulate an ischemic model in vitro. Cell viability, lactate dehydrogenase (LDH) leakage and cell apoptosis were detected following 12 h of exposure to OGD. In addition, the levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑6, IL‑1β, total antioxidant capacity, intercellular adhesion molecule (ICAM)‑1, vascular cell adhesion molecule (VCAM)‑1, chemokine (C‑X‑C motif) ligand (CXCL)‑10, heme oxygenase (HO)‑1 and superoxide dismutase (SOD)‑1 were measured. Pre‑treatment with FTY720 or vitamin E significantly elevated the cell viability and decreased LDH release and number of apoptotic cells. Combination treatment with FTY720 and vitamin E demonstrated a synergistic protective effect on OGD‑induced cell viability, toxicity and apoptosis. Pre‑treatment with FTY720 markedly reduced the release of IL‑1β, TNF‑α, IL‑6, ICAM‑1, VCAM‑1 and CXCL‑10, and pre‑treatment with vitamin E increased the levels of antioxidant, HO‑1 and SOD‑1. However, pre‑treatment with FTY720 combined with vitamin E revealed a synergistic effect. Pre‑treatment with FTY720 combined with vitamin E exerts synergistic neuroprotective effects in the simulated cerebral ischemia in vitro.

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δ-Tocotrienol, a natural form of vitamin E, inhibits pancreatic cancer stem-like cells and prevents pancreatic cancer metastasis.

Husain K, Centeno BA, Coppola D, Trevino J, Sebti SM, Malafa MP

Oncotarget. 2017 May 9;8(19):31554-31567. doi: 10.18632/oncotarget.15767.

Abstract

The growth, metastasis, and chemotherapy resistance of pancreatic ductal adenocarcinoma (PDAC) is characterized by the activation and growth of tumor-initiating cells in distant organs that have stem-like properties. Thus, inhibiting growth of these cells may prevent PDAC growth and metastases. We have demonstrated that δ-tocotrienol, a natural form of vitamin E (VEDT), is bioactive against cancer, delays progression, and prevents metastases in transgenic mouse models of PDAC. In this report, we provide the first evidence that VEDT selectively inhibits PDAC stem-like cells. VEDT inhibited the viability, survival, self-renewal, and expression of Oct4 and Sox2 transcription factors in 3 models of PDAC stem-like cells. In addition, VEDT inhibited the migration, invasion, and several biomarkers of epithelial-to-mesenchymal transition and angiogenesis in PDAC cells and tumors. These processes are critical for tumor metastases. Furthermore, in the L3.6pl orthotopic model of PDAC metastases, VEDT significantly inhibited growth and metastases of these cells. Finally, in an orthotopic xenograft model of human PDAC stem-like cells, we showed that VEDT significantly retarded the growth and metastases of gemcitabine-resistant PDAC human stem-like cells. Because VEDT has been shown to be safe and to reach bioactive levels in humans, this work supports investigating VEDT for chemoprevention of PDAC metastases.

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Alterations of plasma concentrations of lipophilic antioxidants are associated with Guillain-Barre syndrome.

Tang HY, Ho HY, Chiu DT, Huang CY, Cheng ML, Chen CM

Clin Chim Acta. 2017 May 2;470:75-80. doi: 10.1016/j.cca.2017.05.001. [Epub ahead of print]

Abstract

BACKGROUND:

Guillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy resulting in demyelination in peripheral nervous system. Myelin enriched in lipids is easily oxidized by reactive oxygen species during inflammation. Oxidative stress and lipophilic anti-oxidative capacities in GBS patients have not been fully explored. To evaluate the redox status of GBS patients, we measured malondialdehyde (MDA), myeloperoxidase (MPO), lipophilic antioxidants, and tocopherols concentrations in plasma from GBS patients and age-matched healthy controls.

RESULTS:

Concentrations of γ-tocopherol and δ-tocopherol decreased significantly, and α-carotene significantly increased in GBS patients compared to healthy controls. However, no significant changes in MDA and MPO concentrations were detected. In GBS patients, the γ-tocopherol concentration correlated positively with concentrations of δ-tocopherol, α-tocopherol, lutein, Q10, and γ-CEHC, respectively. Similarly, the δ-tocopherol concentration correlated positively with γ-tocopherol, α-tocopherol, lutein, Q10, δ-CEHC, and γ-CEHC concentrations, respectively. The receiver operating characteristics curve analysis showed that γ-tocopherol may serve as a good predictor for GBS.

CONCLUSIONS:

Diminished lipophilic antioxidant defense, mainly γ-tocopherol and δ-tocopherol, in GBS patients accounting for their lowered resistance to reactive oxygen species is probably associated with pathogenesis of GBS, and potentially useful for the development of therapeutic strategies.

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Synergistic Impact of d-δ-Tocotrienol and Geranylgeraniol on the Growth and HMG CoA Reductase of Human DU145 Prostate Carcinoma Cells.

Yeganehjoo H, DeBose-Boyd R, McFarlin BK, Mo H

Nutr Cancer. 2017 May-Jun;69(4):682-691. doi: 10.1080/01635581.2017.1299876. Epub 2017 Mar 31.

Abstract

The growth-suppressive effect of d-δ-tocotrienol and geranylgeraniol is at least partially attributed to their impact on 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting enzyme in the mevalonate pathway that provides essential intermediates for the posttranslational modification of growth-related proteins including RAS. We hypothesize that these agents synergistically impact cell growth based on their complementary mechanisms of action with HMG CoA reductase. d-δ-tocotrienol (0-40 µmol/L; half maximal inhibitory concentration [IC50] = 15 µmol/L) and geranylgeraniol (0-100 µmol/L; IC50 = 60 µmol/L) each induced concentration-dependent suppression of the growth of human DU145 prostate carcinoma cells. Blends of the two agents synergistically suppressed the growth of DU145 cells, with combination index values ranging 0.67-0.75. While 7.5 µmol/L d-δ-tocotrienol and 30 µmol/L geranylgeraniol individually had no impact on cell cycle distribution in DU145 cells, a blend of the agents induced cell cycle arrest at the G1 phase. The synergistic downregulation of the expression of HMG CoA reductase by 7.5 µmol/L d-δ-tocotrienol and 30 µmol/L geranylgeraniol was accompanied by a reduction in membrane K-RAS protein. Our finding supports the cancer chemopreventive action of plant-based diets and their isoprenoid constituents. Properly formulated isoprenoids and derivatives may provide novel approaches in prostate cancer prevention and therapy.

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Inhibitory effects of vitamin E on osteocyte apoptosis and DNA oxidative damage in bone marrow hemopoietic cells at early stage of steroid-induced femoral head necrosis.

Jia YB, Jiang DM, Ren YZ, Liang ZH, Zhao ZQ, Wang YX.

Mol Med Rep. 2017 Apr;15(4):1585-1592. doi: 10.3892/mmr.2017.6160. Epub 2017 Feb 2.

Abstract

Apoptosis and DNA oxidative damage serve significant roles in the pathogenesis of steroid‑induced femoral head necrosis. Vitamin E demonstrates anti‑apoptotic and anti‑oxidant properties. Therefore, the present study investigated the effects of vitamin E on osteocyte apoptosis and DNA oxidative damage in bone marrow hemopoietic cells at an early stage of steroid‑induced femoral head osteonecrosis. Japanese white rabbits were randomly divided into three groups (steroid, vitamin E‑treated, and control groups), each comprising 12 rabbits. Those in the steroid group (group S) were initially injected twice with an intravenous dose of 100 µg/kg Escherichia coli endotoxin, with a 24 h interval between the two injections, and then with an intramuscular dose of 20 mg/kg methylprednisolone, three times at intervals of 24 h in order to establish a rabbit model of osteonecrosis. The vitamin E treated group (group E) received the same treatment as group S, and were administered 0.6 g/kg/d vitamin E daily from the beginning of modeling. The control group (group C) was injected with normal saline at the equivalent dosage and times as the aforementioned two groups. Two time points, weeks 4 and 6 following the completion of modeling, were selected. Osteonecrosis was verified by histopathology with hematoxylin-eosin staining. The apoptosis rate of osteonecrosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The apoptosis expression levels of caspase‑3 and B‑cell lymphoma 2 (Bcl‑2), and DNA oxidative damage of bone marrow hematopoietic cells were analyzed by immunohistochemistry. At weeks 4 and 6 following the completion of modeling, the vacant bone lacunae rates of group E were 15.87±1.97 and 25.09±2.67%, respectively, lower than the results of 20.02±2.21 and 27.79±1.39% for group S; and the osteocyte apoptosis indexes of group E were 20.99±2.95 and 33.93±1.62%, respectively, lower than the results of 26.46±3.37 and 39.90±3.74% from group S. In addition, the Bcl-2 expression at week 4 in the femoral head tissues of group E was higher compared with group S; and the proportion of Bcl‑2‑positive cells of group E was 9.81±1.01%, higher compared with group S at 8.26±1.13%. The caspase‑3 staining data at week 4 in femoral head tissues demonstrated that in the 12 femoral heads of group S, four were negative (32%) and eight were positive (68%); in group E, five were negative (45%) and seven were positive (55%); and in group C, 11 were negative (95%) and one was positive (5%). In addition, the DNA oxidative damage rate at week 4 in the bone marrow hemopoietic cells of group E was (7.24±1.44%), lower compared with group S (11.80±1.26%), and higher compared with group C (5.75±1.47%). Vitamin E is effective in intervening in apoptosis through decreasing caspase‑3 expression and upregulating Bcl‑2 expression, and by alleviating DNA oxidative damage in bone marrow hemopoietic cells at the early stage of steroid‑induced femoral head necrosis in rabbit models.

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Antioxidant activity of amino acids in soybean oil at frying temperature: Structural effects and synergism with tocopherols.

Hwang HS, Winkler-Moser JK.

Food Chem. 2017 Apr 15;221:1168-1177. doi: 10.1016/j.foodchem.2016.11.042. Epub 2016 Nov 9.

Abstract

The purpose of this study was to evaluate amino acids as natural antioxidants for frying. Twenty amino acids were added to soybean oil heated to 180°C, and the effects of amino acid structure on the antioxidant activity were investigated. Amino acids containing a thiol, a thioether, or an extra amine group such as arginine, cysteine, lysine, methionine, and tryptophan had the strongest antioxidant activities. At 5.5mM, these amino acids had stronger antioxidant activities than 0.02% (1.1mM) tert-butylhydroquinone (TBHQ). A functional group such as an amide, carboxylic acid, imidazole, or phenol appeared to negatively affect amino acid antioxidant activity. Synergism between amino acids and tocopherols was demonstrated, and we found that this synergistic interaction may be mostly responsible for the antioxidant activity that was observed. In a frying study with potato cubes, 5.5mM l-methionine had significantly stronger antioxidant activity than 0.02% TBHQ.

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Chemical composition of Brazilian chia seeds grown in different places

da Silva BP, Anunciação PC, Matyelka JC, Della Lucia CM, Martino HS, Pinheiro-Sant'Ana HM.

Food Chem. 2017 Apr 15;221:1709-1716. doi: 10.1016/j.foodchem.2016.10.115. Epub 2016 Nov 2.

Abstract

This study investigated and compared the occurrence and concentration of macronutrients, moisture, ash, dietary fiber, fatty acids, minerals, carotenoids, vitamins, flavonoids, phenolic compounds, antioxidant activity, phytate and tannin in Brazilian chia seeds grown in the states of Mato Grosso (MT) and Rio Grande do Sul (RS). High concentrations of lipids (31.2g.100g-1, on average), proteins (18.9g.100g-1, on average), dietary fiber (35.3g.100g-1, on average), vitamin E (8,203.6μg.100g-1, on average) were observed. Similar values for total phenolic compounds and phytic acid in chia seeds from both regions were observed. Chia grown in RS showed higher antioxidant activity than chia grown in MT, and the tannin concentrations were higher in chia seeds grown in Mato Grosso (19.08±1.08eq.catequina/gsample). In conclusion, Brazilian chia seeds showed high concentrations of lipids, proteins, total dietary fiber, minerals and vitamin E.

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Attenuating Effect of Zinc and Vitamin E on the Intestinal Oxidative Stress Induced by Silver Nanoparticles in Broiler Chickens.

Song Z, Lv J, Sheikhahmadi A, Uerlings J, Everaert N.

Biol Trace Elem Res. 2017 Apr 14. doi: 10.1007/s12011-017-1016-0. [Epub ahead of print]

Abstract

Silver nanoparticles (AgNPs) have been increasingly used as antimicrobial and disinfectant. However, intestinal model studies have shown that AgNPs induce oxidative stress. Hence, this study aims to investigate the effects of dietary supplemental zinc (Zn) and vitamin E (VE; α-tocopherol acetate) on attenuating AgNP-induced intestinal oxidative stress in broiler chickens. The chickens were divided into two groups as follows: (1) control group fed with a corn-soybean meal basal diet and (2) nano group, received drinking water containing 1000 mg/kg AgNPs. All the nano-exposed birds were divided into six dietary treatment groups, namely, the basal diets supplemented with (1) 60 mg/kg Zn as ZnSO4, (2) 120 mg/kg Zn, (3) 100 mg/kg VE, (4) 200 mg/kg VE, (5) 60 mg/kg Zn and 100 mg/kg VE, and (6) 120 mg/kg Zn and 200 mg/kg VE. Results showed that the AgNPs significantly reduced the body weights of the broilers after 42 days of oral administration of AgNPs (P < 0.05), and this effect was not alleviated by any of the dietary treatments. The activity of superoxide dismutase (CuZn-SOD) increased in all the AgNP-treated birds (P < 0.05); however, CuZn-SOD did not increase in birds fed with basal diet supplemented with 200 mg/kg VE. In this treatment, the VE exerted an antioxidant effect to prevent the activation of the CuZn-SOD enzyme. Furthermore, supplementing Zn increased the activities of catalase and glutathione peroxidase in the jejunal mucosa (P < 0.05), which were accompanied with increased malondialdehyde levels (P < 0.05) in the broilers. AgNP exposure resulted in a significant messenger RNA (mRNA) upregulation of toll-like receptor 4 (TLR4) and TLR2-1 in the jejunal mucosa (P < 0.05). However, supplemental ZnVE did not reduce TLRs’ mRNA expression, except for the diminished TLR2-1 mRNA levels in birds fed with basal diet supplemented with 120 mg/kg Zn and 200 mg/kg VE. We concluded that although dietary Zn and VE supplementation did not attenuate growth depression effect of AgNP, it however attenuates intestinal oxidative stress in AgNP-treated broiler chickens.

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The Effects of Omega-3 Fatty Acids and Vitamin E Co-Supplementation on Indices of Insulin Resistance and Hormonal Parameters in Patients with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

Ebrahimi FA, Samimi M, Foroozanfard F, Jamilian M, Akbari H, Rahmani E, Ahmadi S, Taghizadeh M, Memarzadeh MR, Asemi Z.

Exp Clin Endocrinol Diabetes. 2017 Apr 13. doi: 10.1055/s-0042-117773. [Epub ahead of print]

Abstract

This study was conducted to determine the effects of omega-3 fatty acids and vitamin E co-supplementation on indices of insulin resistance and hormonal parameters in women with polycystic ovary syndrome (PCOS). This randomized double-blind, placebo-controlled trial was done on 68 women diagnosed with PCOS according to the Rotterdam criteria aged 18-40 years old. Participants were randomly assigned into 2 groups to receive either 1 000 mg omega-3 fatty acids from flaxseed oil containing 400 mg α-Linolenic acid plus 400 IU vitamin E supplements (n=34) or placebo (n=34) for 12 weeks. Hormonal parameters were quantified at the beginning of the study and after 12-week intervention. After 12 weeks of intervention, compared to the placebo, omega-3 fatty acids and vitamin E co-supplementation resulted in a significant decrease in insulin (-1.0±3.5 vs. +2.7±6.6 µIU/mL, P=0.004), homeostasis model of assessment-estimated insulin resistance (-0.2±0.8 vs. +0.6±1.5, P=0.005), homeostasis model of assessment-estimated B cell function (-4.3±14.3 vs. +10.5±24.5, P=0.004) and a significant increase in quantitative insulin sensitivity check index (+0.006±0.02 vs. -0.01±0.04, P=0.008). Supplementation with omega-3 fatty acids plus vitamin E led to significant reductions in serum total testosterone (-0.5±0.7 vs. -0.1±0.5 ng/mL, P=0.008) and free testosterone (-1.2±2.1 vs. -0.2±1.7, P=0.04) compared to the placebo group. We did not observe any significant effect of omega-3 fatty acids and vitamin E co-supplementation on fasting plasma glucose and other hormonal profiles. Omega-3 fatty acids and vitamin E co-supplementation for 12 weeks in PCOS women significantly improved indices of insulin resistance, total and free testosterone.

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Gamma-tocotrienol profoundly alters sphingolipids in cancer cells by inhibition of dihydroceramide desaturase and possibly activation of sphingolipid hydrolysis during prolonged treatment.

Jang Y, Rao X, Jiang Q

J Nutr Biochem. 2017 Apr 12;46:49-56. doi: 10.1016/j.jnutbio.2017.04.003. [Epub ahead of print]

Abstract

Vitamin E gamma-tocotrienol (γTE) is known to have anticancer effects, but mechanisms underlying these actions are not clear. Here using liquid chromatography tandem mass spectrometry, we show that γTE induced marked changes of sphingolipids including rapid elevation of dihydrosphingosine and dihydroceramides (dhCers) in various types of cancer cells. The elevation of dihydrosphingolipids coincided with increased cellular stress, as indicated by JNK phosphorylation, and was prior to any sign of induction of apoptosis. Chemically blocking de novo synthesis of sphingolipids partially counteracted γTE-induced apoptosis and autophagy. Experiments using 13C3, 15N-labeled l-serine together with enzyme assays indicate that γTE inhibited cellular dihydroceramide desaturase (DEGS) activity without affecting its protein expression or de novo synthesis of sphingolipids. Unlike the effect on dhCers, γTE decreased ceramides (Cers) after 8-h treatment but increased C18:0-Cer and C16:0-Cer after 16 and 24 h, respectively. The increase of Cers coincides with γTE-induced apoptosis and autophagy. Since γTE inhibits DEGS and decreases de novo Cer synthesis, elevation of Cers during prolonged γTE treatment is likely caused by sphingomeylinase-mediated hydrolysis of sphingomyelin. This idea is supported by the observation that an acid sphingomeylinase inhibitor partially reversed γTE-induced cell death. Our study demonstrates that γTE altered sphingolipid metabolism by inhibiting DEGS activity and possibly by activating SM hydrolysis during prolonged treatment in cancer cells.

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