Alpha-tocopherol potentiates the cervical resistance decreasing effects of COX-inhibitors in pregnant rats: the putative role of cyclooxygenase-2 inhibition

Kothencz A, Hajagos-Toth J, Szucs KF, Schaffer A, Gaspar R

J Pharmacol Exp Ther. 2018 Nov 15. pii: jpet.118.251850. doi: 10.1124/jpet.118.251850. [Epub ahead of print]

Abstract

Vitamin E and their analogues as antioxidant and lipid soluble compounds can have diverse effects on the physiological processes. By binding to receptors and enzymes, they may modify the action of drugs. It has been proved that alpha-tocopherol succinate modifies the effects of β2 agonist terbutaline and cyclooxygenase (COX) inhibitors on rat trachea and myometrium. Our aim was to investigate how alpha-tocopherol and COX inhibitors may influence cervical resistance in rats. The cervical resistance of non-pregnant and 22-day-pregnant Sprague-Dawley rats was determined in an isolated organ bath in vitro. Alpha-tocopherol-succinate (10-7 M) was used, while the COX non-selective diclofenac (10-6 M), the COX-2 selective rofecoxib (10-6 M) and the COX-1 selective SC-560 (10-6 M) were applied as inhibitors. The COX activities of the cervices were measured by enzyme-immunoassay. The modifying effect of single doses of COX-inhibitors and tocopherol on the onset of labor was investigated in vivo. The cervical resistance of non-pregnant samples was not changed by either alpha-tocopherol or COX inhibitors. On pregnant cervices, tocopherol, diclofenac or rofecoxib pretreatment decreased cervical resistance that was further reduced by COX-inhibitors after pretreatment with tocopherol. Alpha-tocopherol elicited a significant COX-2 enzyme inhibition in pregnant cervical samples. By co-administration of tocopherol and rofecoxib, the parturition was initiated earlier than in the other groups. It is supposed that COXs play a significant role not only in cervical ripening, but also in the contraction of the cervical smooth muscle a few hours before parturition. This latter action may be developed by COX-2 liberated prostaglandins.

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Vitamin E intake and risk of stroke: a meta-analysis

Cheng P, Wang L, Ning S, Liu Z, Lin H, Chen S, Zhu J

Br J Nutr. 2018 Nov;120(10):1181-1188. doi: 10.1017/S0007114518002647.

Abstract

Findings from observational studies on the associations between vitamin E intake and stroke risk remain controversial, and the dose-response relationship between vitamin E intake and risk of stroke remains to be determined. We conducted a meta-analysis of prospective studies aiming to clarify the relationships between vitamin E intake and risk of stroke. Relevant studies were identified by searching online databases through to June 2018. We computed summary relative risks (RR) with corresponding 95 % CI. Among 3156 articles retrieved from online databases and relevant bibliographies, nine studies involving 3284 events and 220 371 participants were included in the final analyses. High dietary vitamin E intake was inversely associated with the risk of overall stroke (RR=0·83, 95 % CI 0·73, 0·94), and with the risk of stroke for individuals who were followed-up for <10 (RR=0·84, 95 % CI 0·72, 0·91). There was a non-linear association between dietary vitamin E intake and stroke risk (P=0·0249). Omission of any single study did not alter the summary result. In conclusion, this meta-analysis suggests that there is a significant inverse relationship between dietary vitamin E intake and stroke risk. This meta-analysis provides evidence that a higher dietary vitamin E intake is associated with a lower stroke risk.

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Gamma-Tocotrienol Attenuates the Hepatic Inflammation and Fibrosis by Suppressing Endoplasmic Reticulum Stress in Mice

Kim Y, Natarajan SK, Chung S

Mol Nutr Food Res. 2018 Nov;62(21):e1800519. doi: 10.1002/mnfr.201800519. Epub 2018 Sep 9.

Abstract

SCOPE:

Gamma-tocotrienol (γT3), an unsaturated isoform of vitamin E, is implicated in the hepatoprotective effects. The aim is to determine the effectiveness of γT3 on nonalcoholic fatty liver disease (NAFLD).

METHODS AND RESULTS:

C57BL/6 male mice are fed a diet containing high fat (45%) and cholesterol (0.2%) along with sucrose drink (HFCS) or HFCS diet supplemented with 0.1% γT3 (HFCS + γT3). The inclusion of γT3 robustly decreases the HFCS diet-induced de novo lipogenesis (DNL), ER stress, and inflammation leading to reduced hepatic steatosis and fibrosis. Next, mice are fed a methionine- and choline-deficient (MCD) diet or MCD diet with γT3 (MCD + γT3). The γT3 supplementation significantly reduces the MCD diet-induced hepatic ER stress and fibrosis despite the minimal impact on steatosis. To further investigate the role of ER stress, the mice with genetic ablation of CHOP are fed an MCD or MCD + γT3 diet. CHOP deletion abolishes the γT3-mediated suppression of hepatic fibrosis, suggesting that modulation of ER stress is a prerequisite to inhibit hepatic inflammation and fibrosis.

CONCLUSION:

γT3 supplementation is effective in attenuating NAFLD and fibrosis through a synergistic mechanism of decreased DNL and hepatic ER stress. This work strongly supports the translational potential of γT3 supplementation against NAFLD.

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Vitamin E deficiency in South Asian population and the therapeutic use of alpha-tocopherol (Vitamin E) for correction of anemia

Jilani T, Iqbal MP

Pak J Med Sci. 2018 Nov-Dec;34(6):1571-1575. doi: 10.12669/pjms.346.15880.

Abstract

Mild to moderate vitamin E deficiency because of inadequate consumption of vitamin E-rich foods and intestinal fat malabsorption is common in growing children, women of reproductive age and elderly South Asian population. Severe vitamin E deficiency may lead to peripheral and motor neurodegenerative diseases (e.g ataxia and motor skeletal myopathy), impaired immune response and free radical-induced hemolytic anemias. Vitamin E insufficiency and/or deficiency status in the general Pakistani population has not been sufficiently investigated. Moreover, there are challenges in determining vitamin E status in apparently healthy humans due to variations in their age, sources of consumed vitamin E and plasma lipid levels. Oxidative stress-induced reactive oxygen species have been shown to cause ineffective erythropoiesis and enhanced lysis of erythrocytes in some of the experimental animals and humans. Several studies on patients with various types of inherited hemolytic anemias, chronic renal disease, premature low birth infants and apparently healthy humans have shown that vitamin E might be therapeutically effective in the prevention and/ or treatment of anemia in these subjects.

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Effect of vitamin C and vitamin E on lung contusion: A randomized clinical trial study

Abdoulhossein D, Taheri I, Saba MA, Akbari H, Shafagh S, Zataollah A

Ann Med Surg (Lond). 2018 Nov 9;36:152-157. doi: 10.1016/j.amsu.2018.10.026. eCollection 2018 Dec.

Abstract

There is association between lung contusion (lC) and a progressive inflammatory response. The protective effect of vitamin C and vitamin E, as strong free radical scavengers on favourite outcome of (LC) in animal models, has been confirmed.

DESIGN:

to evaluate the effect of vitamins, E and C on arterial blood gas (ABG) and ICU stay, in (LC), with injury severity score (ISS) 18 ± 2, due to blunt chest trauma.

METHODS:

This study was a randomized, double-blind, placebo-controlled clinical trial. Patients with (ISS) 18 ± 2 blunt chest trauma, who meet criteria, participated in the study. A total of 80 patients from Feb 2015 to Jun2018and were randomly divided into 4 groups. Patients received intravenous vitamin E (1000IU mg), was (group I); intravenous vitamin C (500) (group II). Vitamin C + vitamin E = (group III), and intravenous distilled water = (control group) or (group IV). ABG, serum cortisol, and CRP levels were determined at baseline, 24 h and 48 h after the intervention.

RESULTS:

a significant decrease in ICU stay in group III compared to other groups (p < 0.001). Co-administration of vitamin C and vitamin Eshowed significant increases pH (values to reference range from acidemia”), oxygen pressure, and oxygen saturation in group III compared to other groups (p < 0.001). A significant decrease in carbon dioxide pressure was also detected after receiving vitamin C and vitamin E in group III, compared to other groups (p < 0.001). There was no significant difference cortisol and CRP levels between groups after the intervention.

CONCLUSION:

Co-administration of vitamin C and vitamin E, improve the ABG parameters and reduce ICU stay.

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Testicular injury induced by DBP involved in activation of ERK pathway in KM mice

Li J, Wu Z, Cheng J

Wei Sheng Yan Jiu. 2018 Nov;47(6):956-962.

Abstract

OBJECTIVE:

To investigate the role of extracellular regulated protein kinase( ERK) pathway activation in the testicular injury induced by dibutyl phthalate( DBP) in KM mice.

METHODS:

A total of fifty-six male KM mice were randomly divided into 8 groups: control group, 50 mg/( kg·d) DBP group, 50 mg/( kg·d) vitamin E( VE)group, 2 mg/( kg·d) nimodipine( Ni) group, DBP + VE group, DBP + Ni group, Ni +VE group and DBP + Ni + VE group. After consecutive 28 days of treatment, the body weight, testis weight, organ coefficient and sperm density of mice were measured. The histomorphological damage of testis was observed by light microscope. The contents of reactive oxygen species( ROS) and malondialdehyde( MDA) in testicular homogenate of mice in each group were detected by DCFH-DA fluorescence and thiobarbituric acid( TBA) colorimetric method, respectively. The contents of calmodulin( CaM) and level of phosphorylated ERK( p-ERK) were measured by enzyme-linked immunosorbent assay( ELISA).

RESULTS:

Compared with control group, the body weight, testis weight and testicular organ coefficient of mice in 50 mg/( kg·d) DBP group decreased to( 36. 48 ±0. 99) g, ( 0. 25 ± 0. 01) g, ( 0. 54 ± 0. 09) %( P < 0. 05), sperm density decreased to( 11. 70 ± 0. 23) × 10~6/m L( P < 0. 05), and the degree of testicular tissue injury increased with the fluorescence intensity of ROS and the content of MDA increased to( 1698. 18 ± 77. 58), ( 1. 65 ± 0. 13) μmol/g prot( P < 0. 05) respectively. Meanwhile the content of CaM decreased to( 45. 61 ± 2. 69) μg/m L( P < 0. 05) as well as the level of p-ERK increased to( 1150. 43 ± 48. 79) pg/m L( P < 0. 05). After adding VE as antioxidant and Ni as a calcium channel antagonist, compared with 50 mg/( kg·d) DBP group, the body weight and testicular organ coefficient of mice in DBP + Ni + VE group increased to( 40. 69 ± 0. 75) g, ( 0. 69 ± 0. 03) %( P < 0. 05), sperm density increased to( 13. 50 ± 0. 16) × 10~6/m L( P < 0. 05), and the degree of testicular tissue injury decreased with the fluorescence intensity of ROS and the content of MDA decreased to( 1080. 60 ± 98. 64), ( 1. 06 ± 0. 13) μmol/g prot( P < 0. 05) respectively. Meanwhile the content of CaM increased to( 54. 76 ± 1. 74) μg/m L( P < 0. 05) as well as the level of p-ERK decreased to( 904. 55 ± 64. 73) pg/m L( P < 0. 05).

CONCLUSION:

VE as antioxidant and Ni as calcium channel antagonist can reduce the damage of mouse testicular tissue induced by DBP in varying degrees, suggesting that DBP may activate ERK1/2 pathway through oxidative stress and Ca2 +signal, which may lead to testicular tissue damage in mice.

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Could Nanotechnology Make Vitamin E Therapeutically Effective?

Tamura T, Otulakowski G, Kavanagh BP

Am J Physiol Lung Cell Mol Physiol. 2018 Nov 8. doi: 10.1152/ajplung.00430.2018. [Epub ahead of print]

Abstract

Vitamin E (VitE) has important antioxidant and anti-inflammatory effects and is necessary for normal physiological fuction. α-Tocopherol (α-T), the predominant form of VitE in human tissues, has been extensively studied, yet therapeutic trials of VitE have been uniformly negative. We postulate that a nanoparticle approach might provide effective delivery and therapeutic effect.

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α-Tocopherol Ameliorates Redox Equilibrium and Reduces Inflammatory Response Caused by Chronic Variable Stress

Herbet M, Izdebska M, Piątkowska-Chmiel I, Gawrońska-Grzywacz M, Natorska-Chomicka D, Pawłowski K, Sysa M, Ślaska B, Dudka J

Biomed Res Int. 2018 Nov 8;2018:7210783. doi: 10.1155/2018/7210783. eCollection 2018.

Abstract

Chronic exposure to stress factors contributes to the development of depression by generating excess of reactive oxygen species which leads to oxidative stress and inflammatory processes. The aim of the study was to assess the potential protective properties of αtocopherolsupplementation on the rats exposed to chronic variable stress (CVS). Male Wistar rats (50-55 days old, weighing 200-250 g) were divided into three groups (n=10): control, stressed, and stressed and receiving (+)-αtocopherol solution in a dose of 100 mg/kg/day. Rats in the stressed groups were exposed to CVS for 40 days. Markers of redox disorders (glutathione reduced and oxidized levels, GSH/GSSG ratio, glutathione peroxidase, glutathione reductase activities, total antioxidant status, and lipid peroxidation) and inflammatory response (IL-1β, IL6, and TNF-α) were determined in the blood. Additionally, molecular biomarkers of depression (expression of Fkbp5 and Tph2) were studied in hippocampus. The biochemical analysis was inconclusive about the presence of oxidative stress in the blood of rats exposed to CVS. However, changes in all parameters suggest presence of redox equilibrium disorders. Similarly, activation of inflammatory processes was observed as a result of CVS. Molecular effects of environmental stress in hippocampus were also observed. Generally, αtocopherolameliorated redox equilibrium disorders, tempered inflammatory response, and protected from changes in determined molecular markers of depression.

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Fertility hormones and vitamin E in active and passive adult male smokers in Calabar, Nigeria

Bassey IE, Gali RM, Udoh AE

PLoS One. 2018 Nov 6;13(11):e0206504. doi: 10.1371/journal.pone.0206504. eCollection 2018.

Abstract

Smoking is an extremely lethal act and is associated with many illnesses. Lately, major concerns that passive smokers face the same health risks as (if not higher than) active smokers have been raised. Some studies have shown that active smoking is associated with low serum levels of vitamins and testosterone. Are these facts also valid in passive smokers? This study investigated the levels of cotinine, testosterone, follicle stimulating (FSH), Luteinizing Hormone (LH), prolactin and vitamin E in male active smokers and compare these with male passive smokers. Serum levels of cotinine, testosterone, FSH, LH, prolactin and vitamin E were determined in 60 cigarette smokers, 60 passive smokers and 60 non-smokers recruited from Calabar metropolis. The hormones were assayed using ELISA and Vitamin E using high performance liquid chromatography. Socio-demographic and anthropometric indices were obtained and data analyzed using PAWstatistic 18. Cotinine levels were significantly (p<0.05) higher in active smokers than in passive smokers and controls. Vitamin E and testosterone were significantly lower in both active (p<0.05) and passive smokers (p<0.05) when compared to non-smokers. The FSH of the active smokers was significantly higher (p = 0.034) than that of the controls while the passive smokers had the highest LH values (p = 0.0001). However, there were no significant variations in the prolactin levels among the three groups. Both passive and active smoking depletes serum vitamins E and lowers testosterone levels. Lower serum vitamin E is pointer to increased oxidative stress which in conjunction with lower testosterone levels may lead to increased incidence of infertility in both active and passive male smokers.

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Vitamin E δ-tocotrienol inhibits TNF-α-stimulated NF-κB activation by up-regulation of anti-inflammatory A20 via modulation of sphingolipid including elevation of intracellular dihydroceramides

Yang C, Jiang Q

J Nutr Biochem. 2018 Nov 3;64:101-109. doi: 10.1016/j.jnutbio.2018.10.013. [Epub ahead of print]

Abstract

Nuclear factor-κB (NF-κB) regulates inflammation and cell survival, and is considered a potential target for anti-inflammatory and anti-cancer therapy. δ-Tocotrienol (δTE), a vitamin E form, has been shown to inhibit NF-κB, but the mechanism underlying this action is not clear. In the present study, we show that δTE inhibited TNF-α-induced activation of NF-κB and LPS-stimulated IL-6 in a dose- and time-dependent manner in Raw 264.7 macrophages. δTE potently inhibited TNF-α-induced phosphorylation of transforming growth factor β-activated kinase 1 (TAK1), an upstream kinase essential for the activation of NF-κB. Interestingly, δTE significantly increased the expression of A20 and to a less extent, cylindromatosis (CYLD), both of which are inhibitors of NF-κB. The importance of induction of A20 in δTE’s anti-NF-κB effect is validated in A20 knockout cells where δTE’s inhibition of NF-κB was largely diminished. In pursuit of the cause for A20 induction, we found that δTE treatment caused rapid and persistent elevation of dihydroceramides, while decreased ceramides initially but increased ceramides during prolonged treatment. These changes of sphingolipids were accompanied by increased cellular stress markers. Importantly, δTE’s induction of A20 and inhibition of NF-κB activation were partially counteracted by myriocin, a potent inhibitor of de novo synthesis of sphingolipids, indicating a critical role of sphingolipid modulation in δTE-mediated effects. Since dihydroceramide has been shown to induce A20 and inhibit NF-κB in RAW cells, we conclude that that δTE inhibits NF-κB activation by enhancing its negative regulator A20 as a result of modulating sphingolipids especially elevation of dihydroceramides.

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