Effects of delta-tocotrienol on obesity-related adipocyte hypertrophy, inflammation and hepatic steatosis in high-fat-fed mice.

Allen L, Ramalingam L, Menikdiwela K, Scoggin S, Shen CL, Tomison MD, Kaur G, Dufour JM, Chung E, Kalupahana NS, Moustaid-Moussa N

J Nutr Biochem. 2017 Oct;48:128-137. doi: 10.1016/j.jnutbio.2017.07.003. Epub 2017 Jul 10.

Abstract

Inflammation is a major underlying cause for obesity-associated metabolic diseases. Hence, anti-inflammatory dietary components may improve obesity-related disorders. We hypothesized that delta-tocotrienol (δT3), a member of the vitamin E family, reduces adiposity, insulin resistance and hepatic triglycerides through its anti-inflammatory properties. To test this hypothesis, C57BL/6J male mice were fed a high-fat diet (HF) with or without supplementation of δT3 (HF+δT3) at 400 mg/kg and 1600 mg/kg for 14 weeks, and they were compared to mice fed a low-fat diet (LF) or HF supplemented with metformin as an antidiabetic control. Glucose tolerance tests were administered 2 weeks prior to the end of treatments. Histology, quantitative polymerase chain reaction and protein analyses were performed to assess inflammation and fatty acid metabolism in adipose and liver tissues. Significant improvements in glucose tolerance, and reduced hepatic steatosis and serum triglycerides were observed in δT3-supplemented groups compared to the HF group. Body and fat pad weights were not significantly reduced in HF+δT3 groups; however, we observed smaller fat cell size and reduced macrophage infiltration in their adipose tissues compared to other groups. These changes were at least in part mechanistically explained by a reduction of mRNA and protein expression of proinflammatory adipokines and increased expression of anti-inflammatory adipokines in HF+δT3 mice. Moreover, δT3 dose-dependently increased markers of fatty acid oxidation and reduced markers of fatty acid synthesis in adipose tissue and liver. In conclusion, our studies suggest that δT3 may promote metabolically healthy obesity by reducing fat cell hypertrophy and decreasing inflammation in both liver and adipose tissue.

Alshiek JA, Dayan L, Asleh R, Blum S, Levy AP, Jacob G

Diabetes Res Clin Pract. 2017 Sep;131:200-207. doi: 10.1016/j.diabres.2017.06.026. Epub 2017 Jul 13.

Abstract

Vascular dysfunction in both conduit arteries and small vessels is a major contributor to the development of cardiovascular disease (CVD) in diabetes mellitus (DM). In diabetes there is a process of systemic chronic inflammation accompanied by high oxidative stress causing a subsequent decrease in vascular reactivity and negatively affect the metabolic processes responsible for functioning of the microvasculature. Vitamin E is classified as an antioxidant due to its ability to scavenge lipid radicals and terminate oxidative chain reactions. We conducted a double-blinded cross-over study with vitamin E versus placebo in individuals with type 2DM and the Hp2-2 genotype and assessed different aspects of peripheral vascular function in these patients. Twenty patients completed the study with 10 individuals in each study cohort. We were able to show significant improvement of indirect indices of vascular function following 8weeks of treatment with vitamin E. This improvement was consistent for weeks even after stopping the vitamin E treatment. We concluded that a pharmacogenomic rationale utilizing the Hp genotype might potentially provide cardiovascular benefit with vitamin E.

Yap WN

J Cosmet Dermatol. 2017 Sep 26. doi: 10.1111/jocd.12421.

Abstract

BACKGROUND:

UV radiation from the sun is the most common environmental stressor to damage the skin. It is now well established that photodamaged skin manifests signs of mild but chronic inflammation, termed as “inflammaging.” Thus, there is an urgent need for anti-inflammatory regimes that can limit the damage caused by inflammation.

OBJECTIVES:

This study aimed to evaluate the possible palliative effects of a new topical nanoemulsion formulation containing tocotrienol-rich fraction (TRF) on UV-induced inflammation (erythema) of human skin.

METHODS:

An in vitro model was used to demonstrate the ability of TRF to alleviate photodamage via attenuation of UV-induced oxidative stress and inflammation. Two ex vivo models (skin antioxidative potential and radical sun protection factor) were used to determine the efficacy of different formulations of TRF on the skin. A UV-induced erythema protection test in 20 subjects was conducted.

RESULTS:

In vitro studies involving HaCaT keratinocytes revealed that TRF possesses marked anti-inflammatory properties, as indicated by the attenuation of UV-induced upregulation of pro-inflammatory cytokines. A 1% TRF formulation was found to be more effective in enhancing the endogenous antioxidative protection of skin compared to 1% TRF in medium chain triglycerides because of its higher penetration kinetic profile. The clinical study showed that formulated TRF was effective in reducing skin redness after UV irradiation as early as after 6 hours of application. A significant depigmentation was also observed in TRF treatment subjects.

CONCLUSION:

TRF may serve as an anti-inflammatory compound that is safe to be applied daily to protect the skin from UV-induced inflammaging.

Zulkapli R, Abdul Razak F, Zain RB

Integr Cancer Ther. 2017 Sep;16(3):414-425. doi: 10.1177/1534735416675950. Epub 2016 Nov 10.

Abstract

Cancers involving the oral cavity, head, and neck regions are often treated with cisplatin. In cancer therapy, the main target is to eliminate unwanted cancerous cells. However, reports on the nonselective nature of this drug have raised few concerns. Incorrect nutritional habits and lifestyle practices have been directly linked to cancer incidence. Nutrients with antioxidant activity inhibit cancer cells development, destroying them through oxidative stress and apoptosis. α-tocopherol, the potent antioxidant form of vitamin E is a known scavenger of free radicals. In vitro study exhibited effective antitumor activity of α-tocopherol on ORL-48 at 2.5 ± 0.42 µg/mL. Cisplatin exhibited stronger activity at 1.0 ± 0.15 µg/mL, but unlike α-tocopherol it exhibited cytotoxicity on normal human epidermal keratinocytes at very low concentration (<0.1 µg/mL). Despite the lower potency of α-tocopherol, signs of apoptosis such as the shrinkage of cells and appearance of apoptotic bodies were observed much earlier than cisplatin in time lapse microscopy. No apoptotic vesicles were formed with cisplatin, instead an increased population of cells in the holoclone form which may suggest different induction mechanisms between both agents. High accumulation of cells in the G0/G1 phase were observed through TUNEL and annexin V-biotin assays, while the exhibition of ultrastructural changes of the cellular structures verified the apoptotic mode of cell death by both agents. Both cisplatin and α-tocopherol displayed cell cycle arrest at the Sub G0 phase. α-tocopherol thus, showed potential as an antitumour agent for the treatment of oral cancer and merits further research.

Reddy VD, Padmavathi P, Bulle S, Hebbani AV, Marthadu SB, Venugopalacharyulu NC, Maturu P, Varadacharyulu NC

Neurotoxicol Teratol. 2017 Sep;63:60-65. doi: 10.1016/j.ntt.2017.07.004. Epub 2017 Aug 1.

Abstract

Chronic and excessive alcohol consumption leads to various neurological diseases. Synaptosomes are ideal organelles to study the functional properties of the brain in alcoholism. This study focuses on the association between oxidative stress and synaptosomal membrane properties in alcohol treated rats. Sixty day old male albino rats were treated with 20% alcohol at 5g/kg body weight/ day for sixty days. Alcohol administration significantly increased the levels of thiobarbituric acid reactive substances (TBARS) and protein carbonyls with decreased catalase, glutathione peroxidase (GPx), superoxide dismutase (SOD) activities and reduced glutathione (GSH) content in synaptosomes. Further, alcohol administration decreased (cholesterol/phospholipids) C/P ratio in synaptosomal membranes, which was further confirmed using 1,6 diphenyl 1,3 hexatriene (DPH) as fluorescent probe. Moreover, alcohol treatment also increased membrane bound Na⁺/K⁺-ATPase, Ca²⁺-ATPase and Mg²⁺-ATPase enzyme activities. Correlation (r) analysis revealed that anisotropic (γ) values were strongly associated with lipid peroxidation (r=0.678) and Na⁺/K⁺-ATPase activity (r=0.793). The results of the present study clearly indicate that lipid peroxidation was positively correlated (r=0.621) with Na⁺/K⁺-ATPase activity and C/P ratio was negatively associated (r=-0.549) in alcohol treated animals. Similar results were found on alcohol treatment (50 and 100mM) of brain synaptosomes in vitro. But with the co-treatment of vitamin E reversed these changes. In conclusion, synaptosomal membranes properties are impaired due to increased oxidative stress, changes in lipid composition, altered fluidity and membrane bound enzyme activities. And treatment with vitamin E renders protection against ethanol-induced membrane alterations.

Zheng XY, Liang J, Li YS, Tu M

J Clin Rheumatol. 2017 Sep 19. doi: 10.1097/RHU.0000000000000587. [Epub ahead of print]

Abstract

Osteoarthritis (OA) is a chronic degenerative joint disease, in which metabolic imbalance in bone is observed. The pathological mechanism of metabolic imbalance is not clear yet, but the nutritional factors, particularly the vitamins, might be intrinsic to the development and progression of OA. In this review article, we have explored databases such as PubMed, Scopus, and Google Scholar articles until the beginning of 2017 and reviewed the role of fat-soluble vitamins in pathological and therapeutic aspects of OA. Vitamin D plays an important role in the development and maintenance of the skeleton, as well as bone and cartilage metabolism, and its deficiency is implicated in the pathological process of OA. Vitamin E enhances chondrocyte growth and exhibits an anti-inflammatory activity, as well as plays an important role in the prevention of cartilage degeneration. In human OA cartilage, vitamin K deficiency produces abnormal growth plate calcification and inappropriate mineralization of cartilage. Thus, these fat-soluble vitamins play a key role in the pathophysiology of OA, and supplementation of these vitamins may provide innovative approaches for OA management. However, vitamin A has a different role, which is a regulator of cartilage and skeletal formation. When metabolite levels of vitamin A are elevated in synovial fluid, they appear to drive OA development. The role of inhibitors of vitamin A here remains unclear. More investigations are needed to examine the effects of fat-soluble vitamins on the various molecular pathways of OA, as well as to assess the efficacy and safety of their usage clinically.

Zhang J, Song W, Sun Y, Shan A

Environ Sci Pollut Res Int. 2017 Sep 16. doi: 10.1007/s11356-017-0104-1. [Epub ahead of print]

Abstract

Currently, public pay more attention to the adverse effect of organophosphate pesticides on human and animal health and on the environment in developing nations. Vitamin E may protect the hepatocyte and increase the function of liver. The study was to investigate the effects of phoxim-induced hepatotoxicity on Sprague Dawley (SD) rats and the protection of vitamin E. SD rats received by gavage 180 mg kg^-1 (per body weight) of phoxim, 200 mg kg^-1 (per body weight) of vitamin E, and phoxim + vitamin E. The results showed that exposure to phoxim elevated liver coefficient; glutamyl transpeptidase (GGT), aspartate aminotransferase, alkaline phosphatase, total bilirubin, total bile acid, and alanine aminotransferase in the serum; ROS in the liver; and the expression of p53, Bax, CYP2E1, ROS, caspase-9, caspase-8, and caspase-3, while phoxim caused a reduction of total protein, albumin, and cholinesterase in the serum; acetylcholinesterase, total antioxidant capacity, glutathione peroxidase, and glutathione in the liver; and the expression of Bcl-2. Vitamin Emodified the phoxim-induced hepatotoxicity by reducing the GGT in the serum, malondialdehyde in the liver, and the expression of CYP2E1 significantly. There were no significant changes of globulin in the serum, the activity of catalase in the liver, as well as expression levels of Fas and Bad in the liver. Overall, subacute exposure to phoxim induced hepatic injury, oxidative stress damage, and cell apoptosis. Vitamin Emodified phoxim-induced hepatotoxicity slightly. And, vitamin E minimized oxidative stress damage and ultrastructural changes in rat hepatocytes notably.

Duan L, Li J, Ma P, Yang X, Xu S

Food Chem Toxicol. 2017 Sep;107(Pt A):47-56. doi: 10.1016/j.fct.2017.06.025. Epub 2017 Jun 15.

Abstract

Millions of people are regularly exposed to ozone, a gas known to contribute significantly to worsening the symptoms of patients with asthma. However, the mechanisms underlying these ozone exacerbation effects are not fully understood. In this study, we examined the exacerbation effect of ozone in OVA-induced asthma mice and tried to demonstrate the protective mechanism of vitamin E (VE). An asthma mouse model was established, and used to identify the exacerbating effects of ozone by assessing cytokine and serum immunoglobulin concentrations, airway leukocyte infiltration, histopathological changes in lung tissues, and airway hyper-responsiveness. We then determined the amount of reactive oxygen species (ROS) accumulated, the extent to which VE induced ROS elimination, and examined the antagonistic effects of VE on the ozone-induced exacerbating effects. This study showed that 1-ppm ozone exposure could exacerbate OVA-induced asthma in mice. More importantly we found that ozone induced oxidative stress in asthmatic airways may lead to the inhibition of Nuclear factor-erythroid 2-related factor 2 (Nrf2), and may subsequently induce even more exaggerated oxidative stress associated with asthma exacerbation. Through VE induced Nrf2 activation and the subsequent increase in Nrf2 target protein expression, this study suggests a novel mechanism for alleviating ozone exacerbated asthma symptoms.

Bivona JJ, Patel S, Vajdy M

Expert Opin Biol Ther. 2017 Sep 14:1-13. doi: 10.1080/14712598.2017.1375096. [Epub ahead of print]

Abstract

INTRODUCTION:

Vitamins E and C are well known small molecules that have been used to maintain health for decades. Recent studies of the cellular and molecular pathways leading to immunomodulation by these molecules have been of interest, as have their anti-oxidant properties and signal transduction pathways for curing or improving infectious diseases and cancer. Areas covered: Herein, the authors provide a definition and the structural classification of vitamins E and C and how these molecules influence cellular function. The studies include in vitro, ex vivo and in vivo studies in animal models as well as clinical trials. The authors give particular focus to the scientifically factual and putative roles of these molecules in innate and adaptive immunomodulation and prevention or cure of diseases. Expert opinion: The antioxidant properties of vitamins E and C are well studied. However, whether there is a link between their antioxidant and immunomodulation properties is unclear. In addition, there is a strong, albeit putative, prevailing notion that vitamin C can prevent or cure infectious diseases or cancer. Presently, while there is proven evidence that vitamin E possesses immunomodulatory properties that may play a positive role in disease outcomes, this evidence is less available for vitamin C.

Gan YL, Fu JY, Lai OM, Chew BH, Yuen KH, Teng KT, Nesaretnam K, Selvaduray KR, Meganathan P

Sci Rep. 2017 Sep 14;7(1):11542. doi: 10.1038/s41598-017-11813-w.

Abstract

Tocotrienols, the unsaturated form of vitamin E, were reported to modulate platelet aggregation and thrombotic mechanisms in pre-clinical studies. Using a Food and Drug Administration (FDA)-approved cartridge-based measurement system, a randomised, double-blind, crossover and placebo-controlled trial involving 32 metabolic syndrome adults was conducted to investigate the effect of palm-based tocotrienols and tocopherol (PTT) mixture supplementation on platelet aggregation reactivity. The participants were supplemented with 200 mg (69% tocotrienols and 31% α-tocopherol) twice daily of PTT mixture or placebo capsules for 14 days in a random order. After 14 days, each intervention was accompanied by a postprandial study, in which participants consumed 200 mg PTT mixture or placebo capsule after a meal. Blood samples were collected on day 0, day 14 and during postprandial for the measurement of platelet aggregation reactivity. Subjects went through a 15-day washout period before commencement of subsequent intervention. Fasting platelet aggregation reactivity stimulated with adenosine diphosphate (ADP) did not show substantial changes after supplementation with PTT mixture compared to placebo (p = 0.393). Concomitantly, changes in postprandial platelet aggregation reactivity remained similar between PTT mixture and placebo interventions (p = 0.408). The results of this study highlight the lack of inhibitory effect on platelet aggregation after short-term supplementation of PTT mixture in participants with metabolic syndrome.