Vitamin E Ameliorates Lipid Metabolism in Mice with Nonalcoholic Fatty Liver Disease via Nrf2/CES1 Signaling Pathway

He W, Xu Y, Ren X, Xiang D, Lei K, Zhang C, Liu D

Dig Dis Sci. 2019 May 10. doi: 10.1007/s10620-019-05657-9. [Epub ahead of print]

Abstract

BACKGROUND:

Vitamin E has been reported to have a beneficial effect on nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanism of action has not yet been clearly defined.

AIM:

We aimed to evaluate the effects and mechanisms of vitamin E on lipid and glucose homeostasis both in vivo and in vitro.

METHODS:

An NAFLD model was established in C57BL/6 mice fed a 30% fructose solution for 8 weeks. Subsequently, NAFLD mice were given vitamin E (70 mg/kg) for 2 weeks. In addition, L02 cells were treated with 5 mM fructose and 100 nM vitamin E to explore the potential mechanisms of action.

RESULTS:

Vitamin E reversed the impaired glucose tolerance of fructose-treated mice. Histopathological examination showed that liver steatosis was significantly relieved in vitamin E-treated mice. These effects may be attributed to the upregulation of nuclear factor erythroid-2-related factor 2 (Nrf2), carboxylesterase 1 (CES1), and downregulated proteins involved in lipid synthesis by vitamin E treatment. In vivo, vitamin E also significantly reduced lipid accumulation in fructose-treated L02 cells, and the Nrf2 inhibitor ML385 reversed the protective effects of vitamin E.

CONCLUSION:

These data indicated that the therapeutic effects of vitamin E on lipid and glucose homeostasis may be associated with activation of the Nrf2/CES1 signaling pathway.

Casati M, Boccardi V, Ferri E, Bertagnoli L, Bastiani P, Ciccone S, Mansi M, Scamosci M, Rossi PD, Mecocci P, Arosio B

Aging Clin Exp Res. 2019 May 3. doi: 10.1007/s40520-019-01209-3. [Epub ahead of print]

Abstract

BACKGROUND:

Vitamin E represents a potent antioxidant and anti-inflammatory system, playing a role in Alzheimer’s disease (AD). Different plasma concentrations of the forms of vitamin E are observed in AD compared to cognitively healthy subjects.

AIM:

Since these modifications may modulate the markers of oxidative stress and cellular aging, we aim to explore the relationship between vitamin E forms and leukocyte telomere length (LTL) in AD.

METHODS:

53 AD subjects and 40 cognitively healthy controls (CTs) were enrolled. The vitamin E forms (α-, β-, γ- and δ-tocopherol, α-, β-, γ- and δ-tocotrienol), the ratio of α-tocopherylquinone/α-tocopherol and 5-nitro-γ-tocopherol/γ-tocopherol (markers of oxidative/nitrosative damage) and LTL were measured.

RESULTS AND DISCUSSION:

Regression model was used to explore the associations of vitamin E forms and LTL with AD. The interaction of LTL in the association between vitamin E forms and AD was tested. AD subjects showed significantly lower concentrations of α-, β-, γ- and δ-tocopherol, α- and δ-tocotrienol, total tocopherols, total tocotrienols and total vitamin E compared to CTs. AD subjects showed higher values of nitrosative/oxidative damage. The adjusted analyses confirmed a significant relationship of AD with plasma concentrations of α- and β-tocopherols, δ-tocotrienol, total tocopherols, total tocotrienol, total vitamin E and oxidative/nitrosative damage. However, nitrosative damage was significantly associated with AD only in subjects with higher LTL and not in those expressing marked cellular aging.

CONCLUSIONS:

Our study confirms the role of vitamin E in AD pathology and indicates that nitrosative damage influences the association with AD only in subjects characterized by longer LTL.

Ibrahim MA, Bakhaat GA, Tammam HG, Mohamed RM, El-Naggar SA

Biomed Pharmacother. 2019 May;113:108731. doi: 10.1016/j.biopha.2019.108731. Epub 2019 Mar 6.

Abstract

BACKGROUND:

Cisplatin (CP) has been used in wide range for cancer treatment. Although nephrotoxicity of CP was the main complication, cardiotoxicity has been reported.

OBJECTIVES:

This study investigates the protective role of green tea extract (GTE) and vitamin E (Vit-E) against CP-induced cardiotoxicity, and assesses their impact on CP antitumor efficacy.

MATERIALS AND METHODS:

Forty-eight male albino Balb/c mice were randomly divided into six groups, 8 per/group (Gp) were included. Gp1 served as control; Gp2 and Gp3 received oral GTE (400 mg/kg) and Vit-E (100 mg/kg) for 30 consecutive days respectively. Gp4 had received CP (7 mg/kg i.p.) once on the 27th day; Gp5 had received GTE (400 mg/kg p.o.) for 30 days and CP (7 mg/kg i.p.) on the 27th day. Gp6 had received Vit-E (100 mg/kg p.o.) for 30 days and CP (7 mg/kg i.p.) on the 27th day. Blood and tissues samples were harvested for biochemical and histopathological investigations. To evaluate the effect of GTE and Vit-E on the antitumor efficacy of CP, 49 female albino mice were inoculated intraperitoneally by Ehrlich ascetic carcinoma -cells (2 × 10⁶/mouse) then treated with none, corn oil, CP, CP/GTE, CP/Vit-E, GTE or Vit-E.

RESULTS:

CP injection significantly increased Troponin I, CPK, CK-MB, malondialdehyde (MDA), and nitric oxide (NO) levels, while glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase levels were significantly reduced with disruption of cardiac muscle fibers, loss of striations, absence of intercalated disc, and the nuclei are pyknotic. Treatment with GTE and Vit-E improve the biochemical and histological parameters. Treatment with CP alone led to eradication of the tumor cells from the tumor-bearing mice. However, co-administration of GTE or Vit-E orally with CP did not interfere with its therapeutic effects.

CONCLUSION:

Treatment with GTE and Vit-E significantly ameliorated the CP cardiotoxicity and improved the myocardial histopathological architecture. GTE and Vit-E may be combined with CP to alleviate cardiotoxicity in cancer chemotherapy without interfering with its antitumor activity.

Erdemli Z, Erdemli ME, Turkoz Y, Gul M, Yigitcan B, Gozukara Bag H

Andrologia. 2019 Apr 17:e13292. doi: 10.1111/and.13292. [Epub ahead of print]

Abstract

Thirty rats, with confirmed pregnancies by vaginal smear, were divided into five groups, each including six rats, as the Control, Corn Oil, Vitamin E, Acrylamide, Vitamin E + Acrylamide groups. The births were monitored on the 21st day to select the male rats, and the selected male rats were decapitated at the end of the 8th week. Oxidant-antioxidant parameters, serum hormone levels and histopathological examinations were performed on testis tissues of the rats. It was found that acrylamide (AA) negatively affected the serum hormone levels (Total Testosterone, Progesterone, FSH, LH, Estradiol), oxidant-antioxidant parameters in the tissues (MDA, GSH, NO, SOD, CAT, TAS, TOS) (p < 0.05) and the histological findings (the Johnson’s score, seminiferous tubule diameter, histopathological images), and Vitamin Eadministration resulted with an increase in the total testosterone, progesterone, FSH, LH, GSH, TAS, NO, SOD, CAT levels (p < 0.05) and an improvement in histopathological findings. Currently, it is almost inevitable to be exposed to food-induced AA toxicity and such toxicity is likely to cause lifelong damage. It was concluded that Vitamin E was able to present a protective effect in the testis tissue against AA toxicity; however, further studies are necessary.

Ranard KM, Kuchan MJ, Erdman JW Jr

Lipids. 2019 Apr 16. doi: 10.1002/lipd.12149. [Epub ahead of print]

Abstract

Of the antioxidant vitamin E isoforms, α-tocopherol (αT) and γ-tocopherol (γT) are the most abundant in the human diet, and αT is consumed from both natural and synthetic sources. αT and γT may differentially impact inflammation and influence cardiovascular outcomes, in part by modulating gene expression. The goal of this study was to compare the effects of natural αT, synthetic αT, and γT on gene expression in two human cell lines. Human aortic smooth muscle cells (HASMC) and endothelial cells (HAEC) were either: (1) treated with 25 μM tocopherolsalone, or (2) pretreated with tocopherols prior to a pro-inflammatory cytokine (tumor necrosis factor-alpha, TNF-α) stimulation. The expression of atherosclerosis-related genes was measured using RT² Profiler PCR arrays. Tocopherol treatments alone did not significantly modulate the expression of genes in unstimulated HASMC or HAEC. TNF-α stimulation significantly upregulated genes involved with apoptosis and stress response in both cell lines. Pretreating cells with tocopherols did not normalize the gene expression changes induced by TNF-α. However, αT pretreatments, but not γT pretreatments, attenuated TNF expression in both HASMC and HAEC. These findings suggest that under stimulated conditions, αT modestly modulates the expression of selective genes and that αT may be more anti-inflammatory than γT.

Russo T, Currò M, Ferlazzo N, Caccamo D, Perrone P, Arena S, Antonelli E, Antonuccio P, Ientile R, Romeo C, Impellizzeri P

Urol Int. 2019 Apr 16:1-7. doi: 10.1159/000499846. [Epub ahead of print]

Abstract

BACKGROUND:

Lichen sclerosus (LS) is a disease of the skin of unclear etiology that can occur in the foreskin. Topical therapy with corticosteroids is recommended, but they can have side effects.

OBJECTIVES:

We aimed to compare the effects of ozonides with vitamin E acetate (OZOILE) versus topical corticosteroid in children undergoing circumcision.

METHOD:

Twenty children undergoing circumcision were treated before surgery: 10 children with OZOILE cream and 10 with 0.1% mometasone furoate once a day for 7 days. Ten age-matched patients with LS of the foreskin without any treatment were recruited as controls. Transcript levels of proinflammatory and anti-inflammatory cytokines and e-cadherin were evaluated in removed foreskins by qRT-PCR.

RESULTS:

OZOILE and steroid topical treatment produced a similar reduction of TNF-α and IL-1β mRNA levels in foreskins from patients with LS when compared to untreated patients (p < 0.001). OZOILE and steroid treatment caused an increase in the transcript levels of IL-13 and e-cadherin in the foreskin of patients affected by LS in comparison to untreated foreskin (p < 0.001).

CONCLUSIONS:

On the basis of our biochemical data, a randomized clinical trial might be useful to verify the actual clinical effect of OZOILE as alternative treatment to corticosteroids in children affected by LS of the foreskin.

Alzoubi KH, Hasan ZA, Khabour OF, Mayyas FA, Al Yacoub ON, Banihani SA, Alomari MA, Alrabadi NN

Physiol Behav. 2019 Apr 13;206:200-205. doi: 10.1016/j.physbeh.2019.04.011. [Epub ahead of print]

Abstract

There is increasing evidence that oxidative stress is a causal factor in different neurodegenerative disorders such as Alzheimer’s disease and epilepsy. High-fat diet (HFD) has been shown to induce oxidative stress and neuronal damage that may increase susceptibility to seizures. The present study was undertaken to investigate the relationships between vitamin E, a potent antioxidant, HFD, and chemically induced seizures, using the PTZ seizure model in rats. Animals were randomly assigned into four groups: control, HFD, vitamin E (Vit E), and high-fat diet with vitamin E (HFD + Vit E) group. Vitamin E and/or HFD were administered to animals for 6 weeks. Thereafter, PTZ seizure threshold was measured in control and treated rats, and different brain regions were analyzed for levels of oxidative stress biomarkers. Current results revealed a significant reduction in PTZ seizure threshold in rats consuming HFD, which could be prevented by vitamin E supplement. Alongside, vitamin E supplement prevented HFD induced changes in oxidative stress biomarkers and capacity enzymes. Therefore, current results suggest that prolonged consumption of HFD increases susceptibility to PTZ induced seizures, which may be related to HFD induced oxidative stress. This increase in the PTZ susceptibility could be prevented by the administration of vitamin E, probably through its antioxidant effect, particularly at the brain hippocampal region.

Zainal Z, Abdul Rahim A, Khaza'ai H, Chang SK

Int J Mol Sci. 2019 Apr 10;20(7). pii: E1764. doi: 10.3390/ijms20071764.

Abstract

Synthetic therapeutic drugs for asthma, a chronic airway inflammation characterised by strong eosinophil, mast cell, and lymphocyte infiltration, mucus hyper-production, and airway hyper-responsiveness, exhibit numerous side effects. Alternatively, the high antioxidant potential of palm oil phytonutrients, including vitamin E (tocotrienol-rich fractions; TRF) and carotene, may be beneficial for alleviating asthma. Here, we determined the therapeutic efficacy of TRF, carotene, and dexamethasone in ovalbumin-challenged allergic asthma in Brown Norway rats. Asthmatic symptoms fully developed within 8 days after the second sensitization, and were preserved throughout the time course via intranasal ovalbumin re-challenge. Asthmatic rats were then orally administered 30 mg/kg body weight TRF or carotene. TRF-treated animals exhibited reduced inflammatory cells in bronchial alveolar lavage fluid. TRF- and carotene-treated rats exhibited notable white blood cell reduction comparable to that from dexamethasone. TRF- and carotene-treatment also downregulated pro-inflammatory markers (IL-β, IL-6, TNF-α), coincident with anti-inflammatory marker IL-4 and IL-13 upregulation. Treatment significantly reduced asthmatic rat plasma CRP and IgE, signifying improved systemic inflammation. Asthmatic lung histology displayed severe edema and inflammatory cell infiltration in the bronchial wall, whereas treated animals retained healthy, normal-appearing lungs. The phytonutrients tocotrienol and carotene thus exhibit potential benefits for consumption as nutritional adjuncts in asthmatic disease.

Sadeghi F, Alavi-Naeini A, Mardanian F, Ghazvini MR, Mahaki B

Int J Vitam Nutr Res. 2019 Apr 8:1-7. doi: 10.1024/0300-9831/a000588. [Epub ahead of print]

Abstract

BACKGROUND:

Polycystic ovary syndrome is one of the most important factors in female infertility. Oxidative stress is likely to contribute to increased insulin and androgen production in the ovaries, as well as probably impairing follicle production.

AIMS:

This study aims to determine the complementary effects of omega-3 and vitamin E supplements on certain oxidative stress indices in obese and overweight women with polycystic ovary syndrome.

MATERIALS AND METHODS:

This double-blind, randomized clinical trial was performed on polycystic ovary syndrome subjects with BMI > 25. Patients were randomly allocated into two groups to receive either 2 g of omega-3 plus 400 IU of vitamin E, or a placebo, for 8 weeks. At the beginning and the end of the study, total antioxidant capacity, glutathione levels, catalase activity, malondialdehyde concentrations, as well as dietary intake and physical activity were evaluated. Statistical analysis was performed using SPSS.

RESULTS:

32 patients in the intervention group and 30 patients in the placebo group completed the study. Co-supplementation of omega-3 and vitamin E significantly increased total antioxidant capacity (mg/dl) (1.15 ± 0.93 vs -0.6 ± 0.72; P < 0.001), catalase activity (IU/L) (1.19 ± 1.06 vs 0.12 ± 0.36; P < 0.001) and glutathione levels (μmol/L) (1.5 ± 1.06 vs 0.23 ± 1.43; P = 0.028). Additionally, a significant reduction of malondialdehyde levels (nmol/L) (-0.34 ± 0.32 vs 0.57 ± 2.20; P = 0.008) was observed, in comparison with placebo.

CONCLUSION:

Co-supplementation with omega-3 and vitamin E had beneficial effect on total antioxidant capacity, malondialdehyde concentrations, glutathione levels and catalase activity.

Bahrami A, Khorasanchi Z, Sadeghnia HR, Tayefi M, Avan A, Ferns GA, Bahrami-Taghanaki H, Ghayour-Mobarhan M

J Affect Disord. 2019 Apr 8;252:68-73. doi: 10.1016/j.jad.2019.04.048. [Epub ahead of print]

Abstract

BACKGROUND:

The inflammation and oxidative stress are thought to play an important role in the etiopathogenesis of some psychological disorders. We aimed to assess the potential relationships between serum fat soluble vitamins (Vitamins A and E), antibody titers to Hsp27 (anti-Hsp27) and hematological markers of inflammation, with mood disorders in a population of adolescent girls.

METHODS:

A total of 563 adolescent girls (Age 12-18 years) were included in the study. The presence and severity of depression, insomnia and sleepiness were assessed using validated questionnaires. Serum vitamins A and E, anti-Hsp27 antibody titers, white blood cell, lymphocyte, neutrophil, platelet counts, and red blood cell distribution width (RDW), were also measured. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and RDW to platelet ratio (RPR) were calculated.

RESULTS:

Serum anti-HSP27 antibody titers, PLR, and RPR values was significantly higher in subjects with a high depression score compared to normal individuals (p < 0.05). However, there was no association between serum inflammatory markers concentrations and sleep disorders; although individuals with insomnia had a lower vitamin E/HDL ratio compared to healthy adolescents. In multivariate logistic regression analyses adjusted for potential confounders, anti-HSP was an independent predictor of severe depression (OR = 5.0, 95% CI: 1.6-15.7, p < 0.05).

LIMITATION:

The cross-sectional design of study and the inclusion of only female adolescents participants are limitations.

CONCLUSION:

Our findings suggest that serum anti-HSP27 antibody titers may be useful biological marker in depressive patients. This finding may support a role of oxidative stress in the etiology of depression, and targeting this pathway may be of value in the treatment of depression.