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.

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.

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.

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.

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.

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 α–tocopherolsupplementation 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 (+)-α–tocopherol 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, α–tocopherolameliorated redox equilibrium disorders, tempered inflammatory response, and protected from changes in determined molecular markers of depression.

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.