Tocotrienol-rich fraction supplementation prevents foetal loss in females mated with corticosterone-treated male Sprague-Dawley rats.

Abd Aziz NAA, Chatterjee A, Chatterjee R, Durairajanayagam D

Andrologia. 2018 Nov 20:e13199. doi: 10.1111/and.13199. [Epub ahead of print]

Abstract

This study examined whether tocotrienol supplementation to corticosterone-treated male rats could prevent foetal loss in females upon their mating. Epididymides of adult male Sprague-Dawley (SD) rats with proven fertility were surgically separated at the testis-caput junction. Twenty-four hours post-surgery, these animals received for 7 days either: tocopherol-stripped corn oil (Control), corticosterone 25 mg/kg s.c. (CORT), CORT 25 mg/kg s.c. and tocotrienol-rich fraction (TRF) 100 mg/kg orally (CORT + TRF) or TRF 100 mg/kg orally (TRF). On day 8, males were cohabited with proestrus females. A spermatozoa-positive vaginal smear indicated pregnancy. Males were euthanised for analysis of testosterone and antioxidant activities. Reproductive organs were weighed. On day 8 of pregnancy, females were laparotomised to count the number of implantation sites. Pregnancy was continued until term. Number of pups delivered and their weights were determined. Data were analysed using ANOVA. Malondialdehyde levels were significantly lower in CORT + TRF group compared with CORT group. Enzymatic antioxidant activities, testosterone level and reproductive organ weights were significantly higher in CORT + TRF group compared with CORT group. Number of implantation sites and live pups delivered, and their birth weights from females mated with CORT + TRF males were significantly higher compared to CORT group. Therefore, TRF prevents foetal loss in females mated with CORT + TRF-treated males.

Malavolta M, Pierpaoli E, Giacconi R, Basso A, Cardelli M, Piacenza F, Provinciali M

Biol Proced Online. 2018 Nov 20;20:22. doi: 10.1186/s12575-018-0087-4. eCollection 2018.

Abstract

Tocotrienols (T3) have been shown to represent a very important part of the vitamin E family since they have opened new opportunities to prevent or treat a multitude of age-related chronic diseases. The beneficial effects of T3 include the amelioration of lipid profile, the promotion of Nrf2 mediated cytoprotective activity and the suppression of inflammation. All these effects may be the consequence of the ability of T3 to target multiple pathways. We here propose that these effects may be the result of a single target of T3, namely senescent cells. Indeed, T3 may act by a direct suppression of the senescence-associated secretory phenotype (SASP) produced by senescent cells, mediated by inhibition of NF-kB and mTOR, or may potentially remove the origin of the SASP trough senolysis (selective death of senescent cells). Further studies addressed to investigate the impact of T3 on cellular senescence “in vitro” as well as in experimental models of age-related diseases “in vivo” are clearly encouraged.

Tanaka-Yachi R, Shirasaki M, Otsu R, Takahashi-Muto C, Inoue H, Aoki Y, Koike T, Kiyose C

Biochem Biophys Res Commun. 2018 Nov 17;506(1):53-59. doi: 10.1016/j.bbrc.2018.10.021. Epub 2018 Oct 15

Abstract

Activation of thermogenic adipocytes (brown and beige) has been considered an attractive target for weight loss and treatment of metabolic disease. Peroxisome proliferator-activated receptor γ co-activator-1 α (PGC1-α) is a master regulator of thermogenic gene expression in thermogenic adipocytes. We previously reported that α-tocopherol upregulated PGC-1α gene expression and promoted thermogenic adipocyte differentiation in mammalian adipocytes. In this study, we investigated the effects of the vitamin E analogs (α-, γ- and δ-tocopherol) on PGC-1α and uncoupling protein 1 (UCP1) gene expression in 3T3-L1 cells. The expression of PGC-1α and UCP1 increased significantly with the addition of δ-tocopherol. In δ-tocopherol-treated cells, nuclear translocation of PGC-1α increased, as did p38 mitogen-activated protein kinase (MAPK) expression and phosphorylation. Our results suggest that p38 MAPK activation by δ-tocopherol contributes to PGC-1α activation and UCP1 induction.

Boonnoy P, Karttunen M, Wong-Ekkabut J

J Phys Chem B. 2018 Nov 15;122(45):10362-10370. doi: 10.1021/acs.jpcb.8b09064. Epub 2018 Nov 6.

Abstract

α-Tocopherols (α-toc) are crucial in protecting biological membranes against oxidation by free radicals. We investigate the behavior of α-toc molecules in lipid bilayers containing oxidized lipids by molecular dynamics (MD) simulations. To verify the approach, the location and orientation of α-toc are first shown to be in agreement with previous experimental results. The simulations further show that α-toc molecules stay inside the lipid bilayer with their hydroxyl groups in contact with the bilayer surface. Interestingly, interbilayer α-toc flip-flop was observed in both oxidized and nonoxidized bilayers with significantly higher frequency in aldehyde lipid bilayer. Free-energy calculations were performed, and estimates of the flip-flop rates across the bilayers were determined. As the main finding, our results show that the presence of oxidized lipids leads to a significant decrease of free-energy barriers and that the flip-flop rates depend on the type of oxidized lipid present. Our results suggest that α-toc molecules could potentially act as high-efficacy scavengers of free radicals to protect membranes from oxidative attack and help stabilize them under oxidative stress.

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.

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.

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.

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.

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.

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.