Vitamin E for the Prevention of Chemotherapy-Induced Peripheral Neuropathy: A meta-Analysis

Jie Chen, Haili Shan, Wenjun Yang, Jiali Zhang, Haibin Dai, Ziqi Ye

Front Pharmacol . 2021 May 13;12:684550. doi: 10.3389/fphar.2021.684550. eCollection 2021.

Abstract

Background: Vitamin E has been increasingly used to prevent chemotherapy-induced peripheral neuropathy (CIPN) in recent years. However, it is still unclear whether vitamin E can effectively prevent CIPN. Methods: We searched all clinical studies in the Embase, Cochrane Library, Clinicaltrials.gov, and PubMed databases from inception to December 2020. We performed a meta-analysis of 9 randomized controlled trials (RCTs) with 486 patients that compared the vitamin E group with the control group. Outcomes of the study were incidence of all-grade CIPN, incidence of severe CIPN, and the total neuropathy scores (TNS). Random effect models were used to make the meta-analysis results more cautious. Results: Notably, vitamin E significantly reduced the incidence of all-grade CIPN (overall risk ratio (RR) = 0.55, 95% CI: 0.36, 0.85, I2 = 77.3%, p = 0.007), and TNS (overall standard mean difference (SMD) = -0.64, 95% CI: 1.03, -0.25, I2 = 42.7%, p = 0.001). However, the results of the subgroup analysis, which included only double-blind RCTs, suggested that vitamin E did not significantly reduce the incidence of all-grade CIPN (overall RR = 0.52, 95% CI: 0.07, 4.06, I2 = 77.5%, p = 0.531). Moreover, there was no significant difference in the incidence of severe CIPN between these two arms (p = 0.440). Conclusion: The results of our meta-analysis suggests that vitamin E has a beneficial effect on the incidence and symptoms of CIPN. However, routine prophylactic use of vitamin E is still not recommended. Moreover, more high-quality double-blind RCTs are needed to further validate the effects of vitamin E in prevention of CIPN.

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Vitamin E regulates bovine granulosa cell apoptosis via NRF2-mediated defence mechanism by activating PI3K/AKT and ERK1/2 signalling pathways

Meimei Wang, Yan Li, Yanxia Gao, Qiufeng Li, Yufeng Cao, Yizhao Shen, Panliang Chen, Jinling Yan, Jianguo Li

Reprod Domest Anim . 2021 May 12. doi: 10.1111/rda.13950. Online ahead of print.

Abstract

High-yield dairy cows are usually subject to high-intensive cell metabolism and produce excessive reactive oxygen species (ROS). Once ROS is beyond the threshold of scavenging ability, it can induce oxidative stress, imperilling the reproductive performance of cows. The study was to investigate the effects of vitamin E (VE) on H2 O2 -induced proliferation and apoptosis of bovine granulosa cells and the underlying molecular mechanism. Granulosa cells were pretreated with VE for 24 hr and then treated with H2 O2 for 6 hr. The results showed that VE treatment decreased the intracellular ROS levels, increased the MDA content, and improved the antioxidant enzyme activity in a dose-dependent manner. Furthermore, VE treatment promoted the proliferation and inhibited apoptosis in granulosa cells by up-regulation of CCND1 and BCL2 levels and down-regulation of P21, BAX, and CASP3 levels. The cytoprotective effects of VE were attributed to the activation of the NRF2 signalling pathway. Knockdown of the NRF2 impaired the cytoprotective effects of VE on granulosa cells. Besides, the PI3K/AKT and ERK1/2, but not the p38 signalling pathway is involved in the regulation of VE-mediated cell proliferation and apoptosis. The PI3K/AKT inhibitor LY294002 and ERK1/2 inhibitor SCH772984 inhibited the VE-induced granulosa cell proliferation and promoted apoptosis, whereas the p38 inhibitor SB203580 had the opposite effects. These results were confirmed by proliferation and apoptosis-related gene expression at mRNA and protein levels. The results also showed that the PI3K/AKT inhibitor LY294002 and ERK1/2 inhibitor SCH772984 inhibited VE-induced NRF2, GCLC, GCLM, and HO-1 expression, whereas the p38 inhibitor SB203580 not. Overall, the results demonstrated that VE-regulated granulosa cell proliferation and apoptosis via NRF2-mediated defence system by activating the PI3K/AKT and ERK1/2 signalling pathway.

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Endogenous vitamin E metabolites mediate allosteric PPARγ activation with unprecedented co-regulatory interactions

Sabine Willems, Leonie Gellrich, Apirat Chaikuad, Stefan Kluge, Oliver Werz, Jan Heering, Stefan Knapp, Stefan Lorkowski, Manfred Schubert-Zsilavecz, Daniel Merk

Cell Chem Biol . 2021 May 12;S2451-9456(21)00212-9. doi: 10.1016/j.chembiol.2021.04.019. Online ahead of print.

Abstract

Vitamin E exhibits pharmacological effects beyond established antioxidant activity suggesting involvement of unidentified mechanisms. Here, we characterize endogenously formed tocopherol carboxylates and the vitamin E mimetic garcinoic acid (GA) as activators of the peroxisome proliferator-activated receptor gamma (PPARγ). Co-stimulation of PPARγ with GA and the orthosteric agonist pioglitazone resulted in additive transcriptional activity. In line with this, the PPARγ-GA complex adopted a fully active conformation and interestingly contained two bound GA molecules with one at an allosteric site. A co-regulator interaction scan demonstrated an unanticipated co-factor recruitment profile for GA-bound PPARγ compared with canonical PPARγ agonists and gene expression analysis revealed different effects of GA and pioglitazone on PPAR signaling in hepatocytes. These observations reveal allosteric mechanisms of PPARγ modulation as an alternative avenue to PPARγ targeting and suggest contributions of PPARγ activation by α-13-tocopherolcarboxylate to the pharmacological effects of vitamin E.

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Low Serum Vitamin E Level Associated with Low Hand Grip Strength in Community-Dwelling Adults: Korean National Health and Nutrition Examination Survey (KNHANES VII) 2016-2018

Yongjae Kim, Sungjae Shin, Namki Hong, Yumie Rhee

Nutrients . 2021 May 11;13(5):1598. doi: 10.3390/nu13051598.

Abstract

This study assessed the association between serum vitamin E levels and hand grip strength (HGS) in community-dwelling adults data of 1011 men aged 50 years and older and 1144 postmenopausal women were analyzed. Low HGS was defined as HGS below the sex-stratified median value. Proportion of low HGS was the greatest in the lowest quintile of serum vitamin E level (<10.51 mg/L, 57.1%), with a decreasing trend toward the highest vitamin E quintile (>17.81 mg/L, 43.6%; p < 0.001). A one-unit (mg/L) decrease in vitamin E levels was associated with lower HGS in men (adjusted beta coefficient -0.10, 95% confidence interval [CI] -0.18 to -0.02, p = 0.019), but not in women (-0.01, 95% CI -0.06 to 0.03, p = 0.550). Compared with the middle quintile (Q3; 12.59-14.69 mg/L), the lowest vitamin E quintile (Q1) was associated with elevated odds of low HGS (adjusted odds ratio [aOR]: 1.38, p = 0.045), independent of sociodemographic factors, health-related lifestyles, comorbidities, dietary intake, and cholesterol level. However, the odds of low HGS did not differ significantly in other vitamin E quintiles (Q2, aOR 1.12; Q4, aOR 1.38; Q5, aOR 1.12; p > 0.05). Individuals with the lowest quintile vitamin E level had elevated odds of low HGS independent of covariates, findings which merit further validation.

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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 (= 28) and complicated pregnancies (= 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 (< 0.05) and lower percentage S-αT (< 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 (< 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, = 0.0049; r = 0.538, < 0.00001) and percentage S-αT (r = 0.399, = 0.001; r = 0.786, < 0.00001) but negatively correlated with cord percentage RRR-αT (r = -0.399, = 0.0009; r = -0.786, < 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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