Molecular dynamics simulation study of the positioning and dynamics of α-tocopherol in phospholipid bilayers

Sepideh Kavousi, Brian R Novak, Xinjie Tong, Dorel Moldovan

Eur Biophys J . 2021 May 29. doi: 10.1007/s00249-021-01548-y. Online ahead of print.

Abstract

Using molecular dynamics simulations, we investigate the interaction of α-tocopherol (α-toc) with dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylcholine (DMPC), palmitoyloleoylphosphatidylcholine (POPC), and palmitoyloleoylphosphatidylethanolamine (POPE) lipid bilayers. The goal is to develop a better understanding of the positioning and orientation of α-toc inside the bilayers; properties of significant relevance to α-toc anti-oxidant activity. We investigated bilayer systems with 128 lipids in the presence of either single or 14 α-toc molecules. The single α-toc bilayer systems were investigated via biased MD simulations in which the potential of mean force (PMF) and diffusivity were obtained as functions of the distance between α-toc head group and bilayer center. The higher α-toc concentration systems were investigated with unbiased MD simulations. For all four bilayers at both concentrations, the simulations show that the most probable location of the α-toc hydroxyl group is just below the lipid carbonyl group. Overall, the simulation results are in good agreement with existing experimental data except for the DMPC bilayer system for which some experiments predict α-toc to be located closer to bilayer center. The flip-flop frequency calculated shows that the α-toc flip-flop rate is sensitive to bilayer lipid type. In particular, α-toc has a much lower flip-flop rate in a POPE bilayer compared to the three PC lipid bilayers due to the smaller area per lipid in the POPE bilayer. For DMPC and POPC, the α-toc flip-flop rates are significantly higher at higher α-toc concentration and this appears to be related to the local structural disruption caused by α-toc clusters spanning the bilayer.

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The Effect of Combined Vitamin C and Vitamin E Supplementation on Oxidative Stress Markers in Women with Endometriosis: A Randomized, Triple-Blind Placebo-Controlled Clinical Trial

Leila Amini, Razieh Chekini, Mohammad Reza Nateghi, Hamid Haghani, Tannaz Jamialahmadi, Thozhukat Sathyapalan, Amirhossein Sahebkar

Pain Res Manag . 2021 May 26;2021:5529741. doi: 10.1155/2021/5529741. eCollection 2021.

Abstract

Background: Endometriosis is a chronic and estrogen-dependent pelvic inflammatory disease, which may have various causes, such as oxidative stress. Dysmenorrhea, dyspareunia, and pelvic pain are well-known symptoms of endometriosis. The present clinical trial assessed the role of supplementation with antioxidant vitamins on the indices of oxidative stress as well as the severity of pain in women with endometriosis.

Materials and methods: We enrolled 60 reproductive-aged (15-45 years) women with pelvic pain in this triple-blind clinical trial. They had 1-3 stages of laparoscopic-proven endometriosis. The participants were randomized to group A (n = 30), given vitamin C (1000 mg/day, 2 tablets of 500 mg each) and vitamin E (800 IU/day, 2 tablets of 400 IU each) combination, or group B (n = 30), given placebo pills daily for 8 weeks.

Results: Following treatment with vitamin C and vitamin E, we found a significant reduction in MDA and ROS compared with the placebo group. There was no significant decline in total antioxidant capacity after treatment. However, the severity of pelvic pain (p value <0.001), dysmenorrhea (p value <0.001), and dyspareunia (p value <0.001) significantly decreased in the treatment group after 8 weeks of supplementation.

Conclusions: The present findings support the potential role of antioxidants in the management of endometriosis. The intake of vitamin C and vitamin E supplements effectively reduced dysmenorrhea severity and improved dyspareunia and severity of pelvic pain.

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Ability of Sodium Dodecyl Sulfate (SDS) Micelles to Increase the Antioxidant Activity of α-Tocopherol

Raffaella Inchingolo, Ipek Bayram, Sibel Uluata, S Sezer Kiralan, Maria T Rodriguez-Estrada, D Julian McClements, Eric A Decker

J Agric Food Chem . 2021 May 26;69(20):5702-5708. doi: 10.1021/acs.jafc.1c01199. Epub 2021 May 12.

Abstract

As emulsifiers become saturated on the surface of an emulsion droplet, any additional emulsifier migrates to the aqueous phase. Continuous phase surfactants have been shown to increase α-tocopherol efficacy, but it is unclear if this is the result of chemical or physical effects. The addition of α-tocopherol to an oil-in-water emulsion after homogenization resulted in a 70% increase of α-tocopherol in the continuous phase when sodium dodecyl sulfate (SDS) was at levels that were greater than the SDS critical micelle concentration. Conversely, when α-tocopherol was dissolved in the lipid before emulsification, continuous phase SDS concentrations did not increase. When SDS concentration led to an increase in the aqueous phase α-tocopherol, the oxidative stability of oil-in-water emulsions increased. Data indicated that the increased antioxidant activity was the result of surfactant micelles being able to decrease the prooxidant activity of α-tocopherol. Considering these results, surfactant micelles could be an important tool to increase the effectiveness of α-tocopherol.

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alpha-Tocopherol supplementation reduces inflammation and apoptosis in high cholesterol mediated nonalcoholic steatohepatitis

Tugce Demirel-Yalciner, Erdi Sozen, Esra Ozaltin, Ali Sahin, Nesrin Kartal Ozer

Biofactors . 2021 May;47(3):403-413. doi: 10.1002/biof.1700. Epub 2021 Jun 8.

Abstract

Inflammation and apoptosis signaling are crucial steps in the progression from nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH). Alpha-tocopherol, the most active form of vitamin E, is an important modulator of signaling mechanisms, but its involvement to cholesterol-induced NASH pathogenesis remains poorly defined. Herein we have reported a novel effect of α-tocopherol in the transition from hepatic steatosis to NASH. High cholesterol diet alone (without α-tocopherol) in rabbits elevated NASH development as indicated by increased inflammatory response, apoptotic activity and liver fibrosis. Such elevation results from induction of signaling mechanisms since the expressions of IL1β, phospho c-Jun/c-Jun ratio, JNK, caspase 9, CHOP and Bax were increased, and recruitment of macrophage, α-smooth muscle actin (α-SMA) and COL1A1 into the liver tissue were induced. Alpha-tocopherol supplementation inhibited inflammatory response, apoptosis and fibrosis development without affecting lipid accumulation in high cholesterol-induced NASH. Specifically, α-tocopherol lowered the inflammatory level as observed by reduced macrophage infiltration and JNK/c-Jun signaling. Lower inflammatory status co-occurred with the reduction of CHOP and Bax expressions as well as fibrosis-related COL1A1 and α-SMA levels. Taken together, α-tocopherol supplementation inhibits cholesterol-induced NASH development by lowering JNK/c-Jun/inflammation axis in addition to JNK/CHOP/apoptosis signaling, which might contribute to resistance against NAFLD/NASH transition.

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Effect of dietary vitamins C and E on the risk of Parkinson’s disease: A meta-analysis

Min Cheol Chang, Sang Gyu Kwak, Soyoung Kwak

Clin Nutr . 2021 May 21;40(6):3922-3930. doi: 10.1016/j.clnu.2021.05.011. Online ahead of print.

Abstract

Background & aims: A neuroprotective effect of dietary vitamins C and E on Parkinson’s disease (PD) has been suggested, however, several human studies have reported controversial results. Therefore, we conducted a meta-analysis on the effect of vitamins C and E on the risk of Parkinson’s disease.

Methods: A comprehensive literature search was conducted using the PubMed, EMBASE, Cochrane Library, and SCOPUS databases for studies published up to January 23, 2021. We included studies that reported (1) intake of vitamins C and E using validated methods; (2) assessment of odds ratio (OR), relative risk (RR), or hazard ratio (HR); and (3) patients with PD identified by a neurologist, hospital records, or death certificates. The Comprehensive Meta-Analysis Software 2 program was used for statistical analyses of the pooled data.

Results: A total of 12 studies (four prospective cohort and eight case-control studies) were included in our meta-analysis. No significant risk reduction was observed in the high vitamin C intake group compared to low intake group. On the other hand, the high vitamin E intake group showed a significantly lower risk of development of PD than the low intake group (pooled OR = 0.799. 95% CI = 0.721 to 0.885).

Conclusions: We conclude that vitamin E might have a protective effect against PD, while vitamin C does not seem to have such an effect. However, the exact mechanism of the transport and regulation of vitamin E in the CNS remains elusive, and further studies would be necessary in this field.

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Dietary Intake of Vitamin E and Fats Associated with Sarcopenia in Community-Dwelling Older Japanese People: A Cross-Sectional Study from the Fifth Survey of the ROAD Study

Yuta Otsuka, Toshiko Iidaka, Chiaki Horii, Shigeyuki Muraki, Hiroyuki Oka, Kozo Nakamura, Takayuki Izumo, Tomohiro Rogi, Hiroshi Shibata, Sakae Tanaka, Noriko Yoshimura

Nutrients . 2021 May 20;13(5):1730. doi: 10.3390/nu13051730.

Abstract

Dietary habits are of considerable interest as a modifiable factor for the maintenance of muscle health, especially sarcopenia. The present study aimed to investigate the association between dietary intake and sarcopenia prevalence in community-dwelling Japanese subjects. This cross-sectional study was conducted using data from the fifth survey of the Research on Osteoarthritis/Osteoporosis against Disability (ROAD) study, and 1345 participants (437 men and 908 women) aged ≥60 years were included in the analysis. Sarcopenia was determined by the definition of the Asian Working Group for Sarcopenia established in 2014, and dietary intake was assessed with the brief-type self-administered diet history questionnaire. Overall, 77 subjects (5.7%) were identified as having sarcopenia, 5.0% of men and 6.1% of women. Multiple logistic regression analysis showed that the odds ratios of sarcopenia for the dietary intake of vitamin E (α-tocopherol, 0.14 (CI 0.04-0.49), β-tocopherol (0.24, CI 0.07-0.78), γ-tocopherol (0.28, CI 0.09-0.87), and fats (fat 0.27, CI 0.08-0.96; monounsaturated fatty acids, 0.22, CI 0.07-0.72, polyunsaturated fatty acids, 0.28, CI 0.09-0.89) at the highest quantile were significantly lower compared with those at the lowest quantile. Therefore, higher dietary intakes of vitamin E and fats would be associated with a lower prevalence of sarcopenia.

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Evaluation of common genetic variants in vitamin E-related pathway genes and colorectal cancer susceptibility

Qiuyi Zhang, Yixuan Meng, Mulong Du, Shuwei Li, Junyi Xin, Shuai Ben, Zhengdong Zhang, Dongying Gu, Meilin Wang

Arch Toxicol . 2021 May 19. doi: 10.1007/s00204-021-03078-0. Online ahead of print.

Abstract

Vitamin E is effective for preventing the risk of cancer. However, few studies have elucidated the mechanism of vitamin E in cancer occurrence. Herein, we aimed to identify the genetic variants in vitamin E-related pathway genes associated with colorectal cancer risk. We applied logistic regression models to assess the association between single-nucleotide polymorphisms (SNPs) in vitamin E-related pathway genes and colorectal cancer risk in the Chinese and European population. The false discovery rate (FDR) method was used to correct multiple comparisons. The mRNA and protein expression analysis were evaluated in public database and in-house RNA-Seq data. SCARB1 rs73227586 was identified significantly increased risk of colorectal cancer in the Chinese population (odd ratio (OR) = 1.46, 95% confidence interval (CI) = 1.22-1.75, P = 2.99 × 10-5). This finding was further validated in the European population (OR = 1.11, 95% CI = 1.02-1.20, P = 1.44 × 10-2). Additionally, the mRNA and protein expression of SCARB1 were markedly up-regulated in colorectal tumor tissues. Moreover, rs73227586 T allele could increase the minimum free energy (MFE) and weaken binding ability to transcription factor ELL2. Our findings indicated that SCARB1 may play a carcinogenic role in colorectal cancer. Genetic variants in vitamin E-related pathway genes may concern to be predictors of colorectal cancer risk.

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Dynamics of Serum Retinol and Alpha-Tocopherol Levels According to Non-Alcoholic Fatty Liver Disease Status

Dongsub Jeon, Minkook Son, Juhyun Shim

Nutrients . 2021 May 19;13(5):1720. doi: 10.3390/nu13051720.

Abstract

The available data on the association between micronutrients in the blood and non-alcoholic fatty liver disease (NAFLD) are limited. To investigate the clinical implications of this relationship, we sought to identify the difference in the serum levels of vitamins A and E according to NAFLD status using data from the seventh Korea National Health and Nutrition Examination Survey. In this cross-sectional study of the Korean population, NAFLD and its severity were defined using prediction models. Differences in the prevalence and severity of NAFLD were analyzed according to serum retinol (vitamin A) and alpha (α)-tocopherol (vitamin E) levels. Serum levels of retinol and α-tocopherol were positively correlated with the prevalence of NAFLD. In most prediction models of the NAFLD subjects, serum retinol deficiency was significantly correlated with advanced fibrosis, while serum α-tocopherol levels did not differ between individuals with or without advanced fibrosis. Similar trends were also noted with cholesterol-adjusted levels of α-tocopherol. In summary, while circulating concentrations of retinol and α-tocopherol were positively associated with the presence of NAFLD, advanced liver fibrosis was only correlated with serum retinol levels. Our findings could provide insight into NAFLD patient care at a micronutrient level.

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Risk of Colorectal Cancer in a Brazilian Population is Differentially Associated with the Intake of Processed Meat and Vitamin E

Radmila Raiani Alves Ribeiro, Isabella Rolim de Brito, Karolline Andrade Souza, Larissa de Castro Souza, Tiago Almeida de Oliveira, Mathias Weller

Nutr Cancer . 2021 May 17;1-10. doi: 10.1080/01635581.2021.1926519. Online ahead of print.

Abstract

The incidence and mortality rates of colorectal cancer (CRC) in Northeast Brazil are increasing. To study the association between CRC and diet, data were obtained from 64 patients with CRC and 123 sex- and age-matched controls. The dietary details were recorded using a validated food frequency questionnaire. Nutrient intake was calculated using Dietsys software (National Cancer Institute, Maryland, USA). In a binary logistic regression model of dietary components (model 1), the chance of CRC increased by 0.2% (odds ratio [OR] = 1.002; 95% confidence interval [CI]: 1.000-1.004) for each gram of processed meat intake per week (p < 0.010). Consumption of eggs decreased the chance by 0.1% per gram (OR = 0.999; 95% CI: 0.998-1.000; p < 0.050). The use of oil (including olive oil) for served food decreased the chance by 1.8% (OR = 0.982; 95% CI: 0.970-0.992) for each time consumed (p < 0.010). In a model of nutritional factors (model 2), intake of vitamin E decreased the chance by 16.8% (OR = 0.832; 95% CI: 0.725-0.940) for each milligram intake per week (p < 0.010). In model 1 and 2 smoking increased the chance of CRC by 10.294 (95%CI: 4.240-27.670) and 2.496 (95% CI: 1.425-3.566) times (p < 0.010; p < 0.010), respectively.

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Simultaneous quantification of vitamin E and vitamin E metabolites in equine plasma and serum using LC-MS/MS

Hadi Habib, Carrie J Finno, Ingrid Gennity, Gianna Favro, Erin Hales, Birgit Puschner, Benjamin C Moeller

J Vet Diagn Invest . 2021 May;33(3):506-515. doi: 10.1177/10406387211005433. Epub 2021 Apr 13.

Abstract

Vitamin E deficiencies can impact normal growth and development in humans and animals, and assessment of circulating levels of vitamin E and its metabolites may be an important endpoint for evaluation. Development of a sensitive method to detect and quantify low concentrations of vitamin E and metabolites in biological specimens allows for a proper diagnosis for patients and animals that are deficient. We developed a method to simultaneously extract, detect, and quantify the vitamin E compounds alpha-tocopherol (α-TP), gamma-tocopherol (γ-TP), alpha-tocotrienol (α-TT), and gamma-tocotrienol (γ-TT), and the corresponding metabolites formed after β-oxidation of α-TP and γ-TP, alpha-carboxymethylbutyl hydroxychroman (α-CMBHC) and alpha- or gamma-carboxyethyl hydroxychroman (α- or γ-CEHC), respectively, from equine plasma and serum. Quantification was achieved through liquid chromatography-tandem mass spectrometry. We applied a 96-well high-throughput format using a Phenomenex Phree plate to analyze plasma and serum. Compounds were separated by using a Waters ACQUITY UPLC BEH C18 column with a reverse-phase gradient. The limits of detection for the metabolites and vitamin E compounds were 8-330 pg/mL. To validate the method, intra-day and inter-day accuracy and precision were evaluated along with limits of detection and quantification. The method was then applied to determine concentrations of these analytes in plasma and serum of horses. Alpha-TP levels were 3-6 µg/mL of matrix; the metabolites were found at much lower levels, 0.2-1.0 ng/mL of matrix.

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