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Tocotrienols Ameliorate Neurodegeneration and Motor Deficits in the 6-OHDA-Induced Rat Model of Parkinsonism: Behavioural and Immunohistochemistry Analysis

Mangala Kumari, Premdass Ramdas, Ammu Kutty Radhakrishnan, Methil Kannan Kutty, Nagaraja Haleagrahara

Nutrients . 2021 May 10;13(5):1583. doi: 10.3390/nu13051583.

Abstract

Parkinson’s disease (PD) is a debilitating neurodegenerative disease, which progresses over time, causing pathological depigmentation of the substantia nigra (SN) in the midbrain due to loss of dopaminergic neurons. Emerging studies revealed the promising effects of some nutrient compounds in reducing the risk of PD. One such nutrient compound that possess neuroprotective effects and prevents neurodegeneration is tocotrienol (T3), a vitamin E family member. In the present study, a single dose intracisternal injection of 250 µg 6-hydroxydopamine (6-OHDA) was used to induce parkinsonism in male Sprague Dawley (SD) rats. Forty-eight hours post injection, the SD rats were orally supplemented with alpha (α)- and gamma (γ)-T3 for 28 days. The neuroprotective effects of α- and γ-T3 were evaluated using behavioural studies and immunohistochemistry (IHC). The findings from this study revealed that supplementation of α- and γ-T3 was able to ameliorate the motor deficits induced by 6-OHDA and improve the neuronal functions by reducing inflammation, reversing the neuronal degradation, and preventing further reduction of dopaminergic neurons in the SN and striatum (STR) fibre density.

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Vitamin E and selenium improve mesenchymal stem cell conditioned media immunomodulatory effects

Fereshteh Ghasemi, Majid Khoshmirsafa, Elahe Safari, Marzieh Asgari, Mehdi Alemrajabi, Shahrzad Nojehdehi, Samane Khorrami

Stem Cell Investig . 2021 May 7;8:9. doi: 10.21037/sci-2020-008. eCollection 2021.

Abstract

Background: Mesenchymal stem cells (MSCs) with immunoregulatory properties affect immune systems. Many studies showed that antioxidants such as vitamin E (Vit E) and selenium (Se) could improve stem cells survival. This study aims to investigate the effects of MSC conditioned media (CM) treated with Vit E and Se on immune cells.

Methods: MSCs were isolated and cultured with Vit E and Se. Immature dendritic cells (DCs) and peripheral blood mononuclear cells (PBMCs) were cultured with MSC CM treated with Vit E and Se. The expression of HLA-DR, CD86, CD40, and CD83 on mature DC were evaluated. DC supernatant and PBMCs supernatant was collected for the study of TGF-β, IL-10, and IL-12. PBMCs evaluated for the expression of T-bet, GATA3, RORγt, and FOXP3.

Results: MSC CM increased CD40 on myeloid DC (mDC). CD40 has been decreased in DC treated with MSC (Vit E) and MSC (Se) CM. HLA-DR expression on DCs and IL-12 level were significantly reduced in MSC (Vit E) CM. IL-10 concentration increased in DCs treated with MSC (Vit E) and MSC (Se) CM. Treatment of PBMCs with MSC CM decreased IL-10 level, FOXP3, and RORγt expression. On the other hand, the MSC (Vit E) CM and MSC (Se) CM decreased the IL-10 level and increased IL-12, T-bet, and RORγt.

Conclusions: According to the results, the treatment of MSC with Vit E and Se enhanced the ability of MSCs to inhibit DCs and improved immunomodulatory effects. Concerning the effect of MSC on PBMC, it seems that it increased RORγt expression through monocytes.

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Vitamin E succinate exerts anti-tumour effects on human cervical cancer cells via the CD47-SIRPɑ pathway both in vivo and in vitro

Xiaoli Huang, Markus Neckenig, Jintang Sun, Di Jia, Yu Dou, Dan Ai, Zhaodi Nan, Xun Qu

J Cancer . 2021 May 5;12(13):3877-3886. doi: 10.7150/jca.52315. eCollection 2021.

Abstract

Vitamin E succinate (RRR-a-tocopheryl succinate, VES) acts as a potent agent for cancer therapy and has no toxic and side effects on normal tissue cells. However, the mechanism by which VES mediates the effects are not yet fully understood. Here, we hypothesised that VES mediates antitumour activity on human cervical cancer cells via the CD47-SIRPɑ pathway in vivo and in vitro. Results indicated that the human cervical cancer HeLa cells treated with VES were more efficiently engulfed by THP-1-derived macrophages. In response to VES, the protein expression of CD47 on cell membranes and the mRNA level of CD47 in different human cervical cancer cells significantly decreased. And the level of calreticulin (CRT) mRNA in the VES-treated cells increased. By contrast, CRT protein expression was not altered. miRNA-155, miRNA-133 and miRNA-326 were up-regulated in the VES-treated HeLa cells. Knocking down miRNA-155 and miRNA-133 by RNA interference increased CD47 protein expression in the VES-treated cells. In vivo efficacy was determined in BALB/C nude mice with HeLa xenografts. Results showed that VES reduced tumour growth, increased overall survival and inhibited CD47 in the tumour transcriptionally and translationally. Furthermore, inflammatory factors (TNF-α, IL-12, IFN-γ, IL-2 and IL-10) in the spleen were altered because of VES treatment. Our results suggest that VES-induced antitumour activity is coupled to the CD47-SIRPɑ pathway in human cervical HeLa cancer cells.

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Association between ApoE status, circulating vitamin A and vitamin E levels with dyslipidemia in aging Chinese adults

Xiaojun Ma, Yujie Guo, Pengfei Li, Jingjing Xu, Yanyan Gao, Xiuwen Ren, Nicholas Van Halm-Lutterodt, Linhong Yuan

Arch Med Res . 2021 May 3;S0188-4409(21)00113-2. doi: 10.1016/j.arcmed.2021.04.007. Online ahead of print.

Abstract

Background: The influence of ApoE or lipid-soluble vitamins on lipid profile has been well documented. However, the association between ApoE status, vitamin A (VA) and vitamin E (VE) with dyslipidemia has been seldom reported. The aim of the present study was to investigate the impact of ApoE status on circulating VA and VE in aging adults with dyslipidemia.

Methods: A total of 1754 Chinese aged 55-75 was recruited from community health centers. They were interviewed to obtain demographic information. Food frequency questionnaire (FFQ) was used to investigate daily food intakes of the participants. Fasting venous blood samples were taken and used for serum lipid profile measurement and ApoE genotyping. Serum VA and VE concentrations were determined by using high-performance liquid chromatography (HPLC).

Results: Serum VE and VA concentrations were circulating lipids and ApoE status dependent. Dyslipidemia subjects showed higher serum TC, TG, HDL-c/LDL-c ratio, VE and lipid-adjusted VE levels than normal subjects. ApoE genotype-dependent differences in serum lipid profile, VE and VA levels were observed in both normal and dyslipidemia subjects. The relationship between circulating VA with dyslipidemia is modifiable by lipid status.

Conclusion: Higher serum VE and lipid adjusted VE levels associated with increased risk of dyslipidemia in aging Chinese adults, especially in ApoE4 carriers. Large scale longitudinal study is required to determine the optimal circulating VE levels in the elderly based on different lipid profiles and ApoE status.

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α-Tocopherol Stereoisomer Profiles in Matched Human Maternal and Umbilical Cord Plasma

Matthew J Kuchan, Stephen J DeMichele, Karen J Schimpf, Xinhua Chen

Curr Dev Nutr . 2021 May 3;5(6):nzab073. doi: 10.1093/cdn/nzab073. eCollection 2021 Jun.

Abstract

Background: α-Tocopherol (αT) is essential for fetal development. One study has shown that the human placenta preferentially transfers the natural stereoisomer, RRR-αT. But prenatal supplements generally contain synthetic αT (S-αT).

Objectives: We aimed to determine if umbilical cord plasma is enriched for RRR-αT in racially diverse neonates from both uncomplicated and complicated pregnancies and if cord RRR-αT enrichment is impacted by maternal αT stereoisomer profile.

Methods: We measured αT and αT stereoisomers in plasma from a randomly selected subset of 66 predominantly black and Hispanic maternal-fetal pairs from the Camden Study involving control (n = 28) and complicated pregnancies (n = 38). We collected maternal plasma at study entry (week 16 gestation; w16) and week 28 gestation (w28) and cord plasma at birth.

Results: RRR-αT was the predominant stereoisomer in all maternal and cord plasma samples, but S-αT stereoisomers were found in most samples and comprised a high percentage of αT in some maternal-neonate pairs. Cord plasma had a higher percentage RRR-αT (P < 0.05) and lower percentage S-αT (P < 0.0001) than w28 plasma. Pregnancy status did not impact maternal or cord plasma concentrations of αT, RRR-αT, or S-αT; except plasma from complicated pregnancies was higher in S-αT at w28 than at w16 (P < 0.05). Maternal w28 αT did not correlate with cord αT. However, both maternal w28 αT and S-αT positively correlated with both cord S-αT (r = 0.340, P = 0.0049; r = 0.538, P < 0.00001) and percentage S-αT (r = 0.399, P = 0.001; r = 0.786, P < 0.00001) but negatively correlated with cord percentage RRR-αT (r = -0.399, P = 0.0009; r = -0.786, P < 0.00001).

Conclusions: The proportion of RRR-αT was higher in cord compared with maternal plasma in both uncomplicated and complicated pregnancies. Our data suggest that maternal S-αT raises cord S-αT and decreases the proportion of RRR-αT in the neonatal circulation. Because the bioactivities of RRR-αT and S-αT differ, this warrants future research to determine the importance of our observations to neonatal αT status.

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Vitamin E at a high dose as an anti-ferroptosis drug and not just a supplement for COVID-19 treatment

Shima Tavakol, Alexander M Seifalian

Biotechnol Appl Biochem . 2021 May 2. doi: 10.1002/bab.2176. Online ahead of print.

Abstract

Even though the neurodegeneration upon vitamin Edeficiency is related to the ferroptosis. Maybe the neu-ral damages in COVID-19 patients are inhibited in partusing vitamin E consumption through an anti-ferroptosismechanism. In conclusion, it might be said that RBCcharacteristics such as RDW-CV% have vital importancein the prognosis of COVID-19 patients, while the ironserum level affects RDW-CV% and RBC volume and needsmore attention to be monitored in patients. Therefore, thetoxic mechanisms behind iron serum levels such as fer-roptosis should be prevented by vitamin E consumptionthroughinhibitinglipoxygenaseandperoxylradicals.Vita-min E supplement at a high dose of 500 mg/kg may alsoact as a treatment drug to inhibit ferroptosis in COVID-19 patients and decline ferroptosis damages to multipleorgans, including lung, kidney, liver, gut, heart, and ner-vous system. Based on some reports, it is leading to viralclearance and inflammation ablation through the T cells modulation.

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Antioxidant vitamins promote anticancer effects on low-concentration methotrexate-treated glioblastoma cells via enhancing the caspase-3 death pathway

Giou-Teng Yiang, Tsu-Yi Chen, Cian Chen, Yu-Ting Hung, Kuan-Chun Hsueh, Tsai-Kun Wu, Ying-Ru Pan, Yi-Chung Chien, Chao-Hsuan Chen, Yung-Lung Yu, Chyou-Wei Wei

Food Sci Nutr . 2021 May 1;9(6):3308-3316. doi: 10.1002/fsn3.2298. eCollection 2021 Jun.

Abstract

Vitamin C and vitamin E are well-known antioxidant vitamins, both of which are also applied as adjunct treatments for cancer therapy. Methotrexate (MTX) is a clinical drug that is used widely for rheumatoid arthritis and cancer treatment. Human glioblastoma multiforme (GBM) is an aggressive malignant brain tumor; the mean survival time for GBM patients is <2 years with traditional therapies. Developing and investigating novel treatments are important for clinical GBM therapy. Therefore, the aim of this study was to investigate whether combined treatment with vitamin C/E and MTX can display anticancer activities on GBM. Our studies showed that MTX displays anticancer effects on GBM in a dose-dependent manner, while vitamins C and E are not cytotoxic to glioblastoma. Importantly, this study showed that vitamins C and E can promote anticancer effects on low-concentration methotrexate-treated glioblastoma. Additionally, this study suggested that MTX alone or combined with vitamins C/E inhibits GBM cell growth via the caspase-3 death pathway.

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The effects of tocotrienols intake on obesity, blood pressure, inflammation, liver and glucose biomarkers: a meta-analysis of randomized controlled trials

Fengxiang Li, Biao Xu, Samira Soltanieh, Fernando Zanghelini, Ahmed Abu-Zaid, Jian Sun

Crit Rev Food Sci Nutr . 2021 Apr 28;1-14. doi: 10.1080/10408398.2021.1911926. Online ahead of print.

Abstract

The objective of this study is to accomplish a systematic review and meta-analysis of all randomized controlled trials that dissected the influence of tocotrienol supplementation on various anthropometric and cardiometabolic indices in all individuals, irrespective of health condition. This research was carried out in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. 17 eligible articles were included in the final quantitative analysis. Current study revealed that tocotrienol consumption was not associated with CRP, WC, MDA, BMI, IL-6, HbA1C, ALT, AST, creatinine TNF-α, FPG, BW, DBP, and SBP. We did observe an overall increase in BW (SMD: 0.063 kg, 95% CI: -0.200, 0.327, p = 0.637) and DBP (SMD: 0.249 mmHg, 95% CI: 0.053, 0.446, p = 0.013). In addition, a significant reduction in SBP was observed (SMD: -0.616 mmHg, 95% CI: -1.123, -0.110, p = 0.017). In summary, our meta-analysis revealed that tocotrienol consumption was associated with increase in BW and DBP and decrease in SBP. Significant associations were not observed for other outcomes.

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Paternal trans-fatty acid and vitamin E diet affects rat offspring’s semen quality and PPARs expression

Narges Khamehiee, Parham Jazireian, Bita Ebrahimi, AliReza Alizadeh, Maryam Shahhoseini

Andrologia . 2021 Apr 27;e14082. doi: 10.1111/and.14082. Online ahead of print.

Abstract

Trans-fatty acids (TFAs) consumption has created concerns regarding male/female reproductive system. However, the effects of TFA in paternal diet on offspring’s reproduction have not been addressed. The purpose of this study is to investigate the effects of rat paternal TFAs and vitamin E consumption on offspring’s sperm quality and expression pattern of peroxisome proliferator-activated receptors (PPARs) in testis tissues. Forty adult male rats were randomly divided into four groups: Control diet (C); Control diet plus TFA (CTH); diet supplemented with vitamin E (E) and a diet containing vitamin E and TFA (ETH). Mother rats had normal diet during gestation period. Three offspring from each group were chosen randomly and their testicular samples were collected, and sperm parameters were measured by CASA. Our results indicate that feeding fathers with TFA can negatively affect offspring’s sperm concentration and motility, while consumption of vitamin E can improve these parameters (p < .05). The paternal diet containing TFA down-regulated the expression of PPARβ and PPARγ genes, whereas vitamin E-containing diet up-regulated the transcription of PPAR genes. In conclusion, TFA intake in paternal diet may have negative effects on reproductive system of the offspring while vitamin E may not diminish these effects.

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