Administration of vitamin E attenuates airway inflammation through restoration of Nrf2 in a mouse model of asthma

Quang Luu Quoc, Tra Cao Thi Bich, Seo-Hee Kim, Hae-Sim Park, Yoo Seob Shin

J Cell Mol Med . 2021 Jun 4. doi: 10.1111/jcmm.16675. Online ahead of print.

Abstract

Accumulating evidence reveals that ROS is one of the key mediators that contribute to the development of asthma. Studies on antioxidants have shown to have beneficial effects on asthma management. However, we still do not know the precise mechanism, and the effects depend on age. This study was conducted to assess the levels of ROS and the effect of antioxidants in younger and older mice using an eosinophilic asthma model. We analyzed airway hyperresponsiveness (AHR), cytokines in bronchoalveolar lavage fluid (BALF), inflammatory cell counts, and the expression levels of NFκB, Nrf2, EPx, and EDN in the lung tissue, as well as the level of ROS in the lung tissue and BALF. The degree of eosinophilia and the levels of IL-5, ROS, and NFκB were significantly increased, whereas the endogenous levels of vitamin E and Nrf2 were decreased in the lung and BALF in the older mice compared to younger mice. The administration of vitamin E attenuated AHR, airway inflammation, and the level of IL-13 and ROS and enhanced the Nrf2 level in the older mice compared to the younger mice. Taken together, vitamin E treatment may have the therapeutic potential through restoration of the Nrf2 level, especially in elderly asthma.

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Topical cream containing nanoparticles with vitamin E to prevent radiodermatitis in women with breast cancer: a clinical trial protocol

Fernanda Mateus Queiróz Schmidt, Carol V Serna González, Rodrigo Calixto Mattar, Luciana Biagini Lopes, Marinilce Fagundes Dos Santos, Vera L C de Gouveia Santos

J Wound Care . 2021 Jun 1;30(Sup6):S44-S50. doi: 10.12968/jowc.2021.30.Sup6.S44.

Abstract

Objective: Little is known about the efficacy of products aiming to prevent radiodermatitis, which affects between 90-95% of women with breast cancer. The use of antioxidants is promising, however, there is a lack of evidenceon their effectiveness. Here, the authors present a clinical trial protocol to evaluate the effects of applying a cream containing nanoparticles with vitamin E to prevent radiodermatitis in patients with breast cancer.

Method: The protocol recommends that 108 women with breast cancer, receiving radiotherapy, are included in this triple-blinded, randomized, controlled study at an oncology hospital. Patients will be divided in three groups of 36 individuals each: group A will receive a cream with lipid nanoparticles and vitamin E, group B will receive a cream without nanoparticles nor vitamin E, and group C will receive a cream with nanoparticles without vitamin E. The primary endpoints will evaluate the incidence, degree, and time of onset of radiodermatitis. The secondary endpoints will focus on the quality of life, symptoms, and local temperature. Patients will be assessed three times a week, from the start of their radiotherapy treatment to two weeks after the last session. This protocol was approved by the research ethics committee of the institutions involved and registered on an international trials database.

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Annatto tocotrienol may help manage blood sugar: RCT

Supplementation with annatto-derived delta-tocotrienol may improve glucose control, inflammation and oxidative stress in people with type 2 diabetes mellitus (T2DM), says a new study from the National University of Medical Sciences in Pakistan.

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δ-Tocotrienol induces apoptosis and inhibits proliferation of nasopharyngeal carcinoma cells

Junjun Shen, Tao Yang, Yiping Tang, Tianyi Guo, Ting Guo, Tao Hu, Feijun Luo, Qinlu Lin

Food Funct . 2021 May 31. doi: 10.1039/d1fo00461a. Online ahead of print.

Abstract

Nasopharyngeal carcinoma has a notably high incidence rate in Southern China, Southeast Asia, North Africa, Middle East, and the Arctic. δ-Tocotrienol is abundant in cereal and has some health benefits. In our recent study, we showed that δ-tocotrienol exerted anti-inflammatory effects in murine macrophages in vitro. The aim of this study was to further investigate the chemopreventive effects of δ-tocotrienol on human CNE1 cells. We showed that δ-tocotrienol induced apoptosis and cell cycle arrest at G0/G1 and M phases in nasopharyngeal carcinoma cells. Microarray analysis revealed that after CNE1 cells were treated with δ-tocotrienol, 169 genes were up-regulated and 167 down-regulated. ERK1/2 was shown to play a vital role in cell cycle arrest by gene chips. The results suggest that δ-tocotrienol induces cell cycle arrest in CNE1 cells via the p16/CDK4/cyclin D1 signaling pathway. Western blots showed that CNE1 apoptosis was related to dysregulated expression of Bax-2 and Bcl-2. Furthermore, caspase-3, -8, -9 up-regulation was related to the apoptotic effect of δ-tocotrienol; therefore, δ-tocotrienol triggers apoptosis in CNE1 cells through caspase-3 signaling. δ-Tocotrienol may potentially be developed as an anti-cancer agent in the management of nasopharyngeal carcinoma.

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Tocotrienols: Dietary Supplements for Chronic Obstructive Pulmonary Disease

Xiangming Ji, Hongwei Yao, Maureen Meister, Douglas S Gardenhire, Huanbiao Mo

Antioxidants (Basel) . 2021 May 31;10(6):883. doi: 10.3390/antiox10060883.

Abstract

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Emphysema and chronic bronchitis are the two major phenotypes of COPD, which have many symptoms, such as dyspnea, chronic cough, and mucus overproduction. Emphysema is characterized by the destruction of the alveolar wall, while chronic bronchitis is characterized by limitations in expiratory airflow. Cigarette smoking is the most significant risk factor for the pathogenesis of COPD in the developed world. Chronic inflammation contributes to the onset and progression of the disease and furthers the risk of comorbidities. Current treatment options and prevention strategies for COPD are very limited. Tocotrienols are a group of vitamin E molecules with antioxidant and anti-inflammatory properties. Individual tocotrienols (α, γ, and δ) have shown their ability to attenuate inflammation specifically via suppressing nuclear factor-κB-mediated cytokine production. The δ- and γ-forms of tocotrienols have been indicated as the most effective in the prevention of macrophage infiltration, production of reactive oxygen species, and cytokine secretion. This review briefly discusses the pathogenesis of COPD and the role of inflammation therein. Furthermore, we summarize the in vitro and in vivo evidence for the anti-inflammatory activity of tocotrienols and their potential application to COPD management. Coupled with the bioavailability and safety profile of tocotrienols, the ability of these compounds to modulate COPD progression by targeting the inflammation pathways renders them potential candidates for novel therapeutic approaches in the treatment of COPD patients.

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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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