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  1. Fulltext Clinically Relevant Genes and Proteins Modulated by Tocotrienols in Human Colon Cancer Cell Lines: Systematic Scoping Review
    Khalid AQ, Bhuvanendran S, Magalingam KB, Ramdas P, Kumari M, Radhakrishnan AK
    Nutrients, 2021 Nov 12;13(11).
    PMID: 34836311 DOI: 10.3390/nu13114056
    The last decade has witnessed tremendous growth in tocotrienols (T3s) research, especially in the field of oncology, owing to potent anticancer property. Among the many types of cancers, colorectal cancer (CRC) is growing to become a serious global health threat to humans. Chemoprevention strategies in recent days are open to exploring alternative interventions to inhibit or delay carcinogenesis, especially with the use of bioactive natural compounds, such as tocotrienols. This scoping review aims to distil the large bodies of literature from various databases to identify the genes and their encoded modulations by tocotrienols and to explicate important mechanisms via which T3s combat CRC. For this scoping review, research papers published from 2010 to early 2021 related to T3s and human CRC cells were reviewed in compliance with the PRISMA guidelines. The study included research articles published in English, searchable on four literature databases (Ovid MEDLINE, PubMed, Scopus, and Embase) that reported differential expression of genes and proteins in human CRC cell lines following exposure to T3s. A total of 12 articles that fulfilled the inclusion and exclusion criteria of the study were short-listed for data extraction and analysis. The results from the analysis of these 12 articles showed that T3s, especially its γ and δ analogues, modulated the expression of 16 genes and their encoded proteins that are associated with several important CRC pathways (apoptosis, transcriptional dysregulation in cancer, and cancer progression). Further studies and validation work are required to scrutinize the specific role of T3s on these genes and proteins and to propose the use of T3s to develop adjuvant or multi-targeted therapy for CRC.
    Matched MeSH terms: Tocotrienols/pharmacology*
  2. Fulltext Tocotrienol-Rich Vitamin E (Tocovid) Improved Nerve Conduction Velocity in Type 2 Diabetes Mellitus Patients in a Phase II Double-Blind, Randomized Controlled Clinical Trial
    Chuar PF, Ng YT, Phang SCW, Koay YY, Ho JI, Ho LS, et al.
    Nutrients, 2021 Oct 25;13(11).
    PMID: 34836025 DOI: 10.3390/nu13113770
    Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFβ-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.
    Matched MeSH terms: Tocotrienols/administration & dosage*
  3. Fulltext The Ameliorative Effects of a Tocotrienol-Rich Fraction on the AGE-RAGE Axis and Hypertension in High-Fat-Diet-Fed Rats with Metabolic Syndrome
    Cheng HS, Ton SH, Tan JBL, Abdul Kadir K
    Nutrients, 2017 Sep 07;9(9).
    PMID: 28880217 DOI: 10.3390/nu9090984
    The clinical value of tocotrienols is increasingly appreciated because of the unique therapeutic effects that are not shared by tocopherols. However, their effect on metabolic syndrome is not well-established. This study aimed to investigate the effects of a tocotrienol-rich fraction (TRF) from palm oil in high-fat-diet-treated rats. Male, post-weaning Sprague Dawley rats were provided high-fat (60% kcal) diet for eight weeks followed by a TRF (60 mg/kg) treatment for another four weeks. Physical, metabolic, and histological changes were compared to those on control and high-fat diets respectively. High-fat feeding for eight weeks induced all hallmarks of metabolic syndrome. The TRF reversed systolic and diastolic hypertension, hypercholesterolemia, hepatic steatosis, impaired antioxidant defense, and myeloperoxidase hyperactivity triggered by the high-fat diet. It also conferred an inhibitory effect on protein glycation to reduce glycated hemoglobin A1c and advanced glycation end products (AGE). This was accompanied by the suppression of the receptor for advanced glycation end product (RAGE) expression in the liver. The treatment effects on visceral adiposity, glycemic control, triglyceride level, as well as peroxisome proliferator-activated receptor α and γ expression were negligible. To conclude, treatment with a TRF exhibited protective effects on the cardiovascular and liver health in addition to the amelioration of plasma redox imbalance and AGE-RAGE activation. Further investigation as a therapy for metabolic syndrome is therefore worthwhile.
    Matched MeSH terms: Tocotrienols/pharmacology*
  4. Fulltext Rice Bran: From Waste to Nutritious Food Ingredients
    Tan BL, Norhaizan ME, Chan LC
    Nutrients, 2023 May 28;15(11).
    PMID: 37299466 DOI: 10.3390/nu15112503
    Rice (Oryza sativa L.) is a principal food for more than half of the world's people. Rice is predominantly consumed as white rice, a refined grain that is produced during the rice milling process which removes the bran and germ and leaves the starchy endosperm. Rice bran is a by-product produced from the rice milling process, which contains many bioactive compounds, for instance, phenolic compounds, tocotrienols, tocopherols, and γ-oryzanol. These bioactive compounds are thought to protect against cancer, vascular disease, and type 2 diabetes. Extraction of rice bran oil also generates various by-products including rice bran wax, defatted rice bran, filtered cake, and rice acid oil, and some of them exert bioactive substances that could be utilized as functional food ingredients. However, rice bran is often utilized as animal feed or discarded as waste. Therefore, this review aimed to discuss the role of rice bran in metabolic ailments. The bioactive constituents and food product application of rice bran were also highlighted in this study. Collectively, a better understanding of the underlying molecular mechanism and the role of these bioactive compounds exerted in the rice bran would provide a useful approach for the food industry and prevent metabolic ailments.
    Matched MeSH terms: Tocotrienols*
  5. Alkaloid extracts of Ficus species and palm oil-derived tocotrienols synergistically inhibit proliferation of human cancer cells
    Abubakar IB, Lim KH, Loh HS
    Nat Prod Res, 2015;29(22):2137-40.
    PMID: 25515603 DOI: 10.1080/14786419.2014.991927
    Tocotrienols have been reported to possess anticancer effects other than anti-inflammatory and antioxidant activities. This study explored the potential synergism of antiproliferative effects induced by individual alkaloid extracts of Ficus fistulosa, Ficus hispida and Ficus schwarzii combined with δ- and γ-tocotrienols against human brain glioblastoma (U87MG), lung adenocarcinoma (A549) and colorectal adenocarcinoma (HT-29) cells. Cell viability and morphological results demonstrated that extracts containing a mixture of alkaloids from the leaves and bark of F. schwarzii inhibited the proliferation of HT-29 cells, whereas the alkaloid extracts of F. fistulosa inhibited the proliferation of both U87MG and HT-29 cells and showed synergism in combined treatments with either δ- or γ-tocotrienol resulting in 2.2-34.7 fold of reduction in IC50 values of tocotrienols. The observed apoptotic cell characteristics in conjunction with the synergistic antiproliferative effects of Ficus species-derived alkaloids and tocotrienols assuredly warrant future investigations towards the development of a value-added chemotherapeutic regimen against cancers.
    Matched MeSH terms: Tocotrienols/isolation & purification; Tocotrienols/pharmacology*
  6. Co-encapsulation of gemcitabine and tocotrienols in nanovesicles enhanced efficacy in pancreatic cancer
    Maniam G, Mai CW, Zulkefeli M, Fu JY
    Nanomedicine (Lond), 2021 02;16(5):373-389.
    PMID: 33543651 DOI: 10.2217/nnm-2020-0374
    Aim: To synthesize niosomes co-encapsulating gemcitabine (GEM) and tocotrienols, and physicochemically characterize and evaluate the antipancreatic effects of the nanoformulation on Panc 10.05, SW 1990, AsPC-1 and BxPC-3 cells. Materials & methods: Niosomes-entrapping GEM and tocotrienols composed of Span 60, cholesterol and D-α-tocopheryl polyethylene glycol 1000 succinate were produced by Handjani-Vila and film hydration methods. Results: The film hydration produced vesicles measuring 161.9 ± 0.5 nm, approximately 50% smaller in size than Handjani-Vila method, with maximum entrapment efficiencies of 20.07 ± 0.22% for GEM and 34.52 ± 0.10% for tocotrienols. In Panc 10.05 cells, GEM's antiproliferative effect was enhanced 2.78-fold in combination with tocotrienols. Niosomes produced a significant ninefold enhancement in cytotoxicity of the combination, supported by significantly higher cellular uptake of GEM in the cells. Conclusion: This study is a proof of concept on the synthesis of dual-drug niosomes and their efficacy on pancreatic cancer cells in vitro.
    Matched MeSH terms: Tocotrienols
  7. Tumor regression and modulation of gene expression via tumor-targeted tocotrienol niosomes
    Tan DM, Fu JY, Wong FS, Er HM, Chen YS, Nesaretnam K
    Nanomedicine (Lond), 2017 Oct;12(20):2487-2502.
    PMID: 28972460 DOI: 10.2217/nnm-2017-0182
    AIM: To develop 6-O-palmitoyl-ascorbic acid-based niosomes targeted to transferrin receptor for intravenous administration of tocotrienols (T3) in breast cancer.

    MATERIALS & METHODS: Niosomes were prepared using film hydration and ultrasonication methods. Transferrin was coupled to the surface of niosomes via chemical linker. Nanovesicles were characterized for size, zeta potential, morphology, stability and biological efficacy.

    RESULTS: When evaluated in MDA-MB-231 cells, entrapment of T3 in niosomes caused 1.5-fold reduction in IC50 value compared with nonformulated T3. In vivo, the average tumor volume of mice treated with tumor-targeted niosomes was 12-fold lower than that of untreated group, accompanied by marked downregulation of three genes involved in metastasis.

    CONCLUSION: Findings suggested that tumor-targeted niosomes served as promising delivery system for T3 in cancer therapy.

    Matched MeSH terms: Tocotrienols/chemistry*
  8. Fulltext Tocotrienol-rich fraction, [6]-gingerol and epigallocatechin gallate inhibit proliferation and induce apoptosis of glioma cancer cells
    Rahman AA, Makpol S, Jamal R, Harun R, Mokhtar N, Ngah WZ
    Molecules, 2014 Sep 12;19(9):14528-41.
    PMID: 25221872 DOI: 10.3390/molecules190914528
    Plant bioactives [6]-gingerol (GING), epigallocatechin gallate (EGCG) and asiaticoside (AS) and vitamin E, such as tocotrienol-rich fraction (TRF), have been reported to possess anticancer activity. In this study, we investigated the apoptotic properties of these bioactive compounds alone or in combination on glioma cancer cells. TRF, GING, EGCG and AS were tested for cytotoxicity on glioma cell lines 1321N1 (Grade II), SW1783 (Grade III) and LN18 (Grade IV) in culture by the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. With the exception of AS, combinations of two compounds were tested, and the interactions of each combination were evaluated by the combination index (CI) using an isobologram. Different grades of glioma cancer cells showed different cytotoxic responses to the compounds, where in 1321N1 and LN18 cells, the combination of EGCG + GING exhibited a synergistic effect with CI = 0.77 and CI = 0.55, respectively. In contrast, all combinations tested (TRF + GING, TRF + EGCG and EGCG + GING) were found to be antagonistic on SW1783 with CI values of 1.29, 1.39 and 1.39, respectively. Combined EGCG + GING induced apoptosis in both 1321N1 and LN18 cells, as evidenced by Annexin-V FITC/PI staining and increased active caspase-3. Our current data suggests that the combination of EGCG + GING synergistically induced apoptosis and inhibits the proliferation 1321N1 and LN18 cells, but not SW1783 cells, which may be due to their different genetic profiles.
    Matched MeSH terms: Tocotrienols/administration & dosage*
  9. Fulltext Production of Nanoemulsions from Palm-Based Tocotrienol Rich Fraction by Microfluidization
    Goh PS, Ng MH, Choo YM, Amru NB, Chuah CH
    Molecules, 2015;20(11):19936-46.
    PMID: 26556328 DOI: 10.3390/molecules201119666
    In the present study, tocotrienol rich fraction (TRF) nanoemulsions were produced as an alternative approach to improve solubility and absorption of tocotrienols. In the present study, droplet size obtained after 10 cycles of homogenization with increasing pressure was found to decrease from 120 to 65.1 nm. Nanoemulsions stabilized with Tween series alone or emulsifier blend Brij 35:Span 80 (0.6:0.4 w/w) homogenized at 25,000 psi and 10 cycles, produced droplet size less than 100 nm and a narrow size distribution with a polydispersity index (PDI) value lower than 0.2. However blend of Tween series with Span 80 produced nanoemulsions with droplet size larger than 200 nm. This work has also demonstrated the amount of tocols losses in TRF nanoemulsion stabilized Tweens alone or emulsifier blend Brij 35:Span 80 (0.6:0.4 w/w) ranged between 3%-25%. This can be attributed to the interfacial film formed surrounding the droplets exhibited different level of oxidative stability against heat and free radicals created during high pressure emulsification.
    Matched MeSH terms: Tocotrienols
  10. Fulltext Synthesis of [18F]F-γ-T-3, a Redox-Silent γ-Tocotrienol (γ-T-3) Vitamin E Analogue for Image-Based In Vivo Studies of Vitamin E Biodistribution and Dynamics
    Roselt P, Cullinane C, Noonan W, Elsaidi H, Eu P, Wiebe LI
    Molecules, 2020 Dec 03;25(23).
    PMID: 33287202 DOI: 10.3390/molecules25235700
    Vitamin E, a natural antioxidant, is of interest to scientists, health care pundits and faddists; its nutritional and biomedical attributes may be validated, anecdotal or fantasy. Vitamin E is a mixture of tocopherols (TPs) and tocotrienols (T-3s), each class having four substitutional isomers (α-, β-, γ-, δ-). Vitamin E analogues attain only low concentrations in most tissues, necessitating exacting invasive techniques for analytical research. Quantitative positron emission tomography (PET) with an F-18-labeled molecular probe would expedite access to Vitamin E's biodistributions and pharmacokinetics via non-invasive temporal imaging. (R)-6-(3-[18F]Fluoropropoxy)-2,7,8-trimethyl-2-(4,8,12-trimethyltrideca-3,7,11-trien-1-yl)-chromane ([18F]F-γ-T-3) was prepared for this purpose. [18F]F-γ-T-3 was synthesized from γ-T-3 in two steps: (i) 1,3-di-O-tosylpropane was introduced at C6-O to form TsO-γ-T-3, and (ii) reaction of this tosylate with [18F]fluoride in DMF/K222. Non-radioactive F-γ-T-3 was synthesized by reaction of γ-T-3 with 3-fluoropropyl methanesulfonate. [18F]F-γ-T-3 biodistribution in a murine tumor model was imaged using a small-animal PET scanner. F-γ-T-3 was prepared in 61% chemical yield. [18F]F-γ-T-3 was synthesized in acceptable radiochemical yield (RCY 12%) with high radiochemical purity (>99% RCP) in 45 min. Preliminary F-18 PET images in mice showed upper abdominal accumulation with evidence of renal clearance, only low concentrations in the thorax (lung/heart) and head, and rapid clearance from blood. [18F]F-γ-T-3 shows promise as an F-18 PET tracer for detailed in vivo studies of Vitamin E. The labeling procedure provides acceptable RCY, high RCP and pertinence to all eight Vitamin E analogues.
    Matched MeSH terms: Tocotrienols/pharmacokinetics*; Tocotrienols/chemistry*
  11. Fulltext The Role of Tocotrienol in Protecting Against Metabolic Diseases
    Pang KL, Chin KY
    Molecules, 2019 Mar 06;24(5).
    PMID: 30845769 DOI: 10.3390/molecules24050923
    Obesity is a major risk factor for diabetes, and these two metabolic conditions cause significant healthcare burden worldwide. Chronic inflammation and increased oxidative stress due to exposure of cells to excess nutrients in obesity may trigger insulin resistance and pancreatic β-cell dysfunction. Tocotrienol, as a functional food component with anti-inflammatory, antioxidant, and cell signaling-mediating effects, may be a potential agent to complement the current management of obesity and diabetes. The review aimed to summarize the current evidence on the anti-obesity and antidiabetic effects of tocotrienol. Previous studies showed that tocotrienol could suppress adipogenesis and, subsequently, reduce body weight and fat mass in animals. This was achieved by regulating pathways of lipid metabolism and fatty acid biosynthesis. It could also reduce the expression of transcription factors regulating adipogenesis and increase apoptosis of adipocytes. In diabetic models, tocotrienol was shown to improve glucose homeostasis. Activation of peroxisome proliferator-activated receptors was suggested to be responsible for these effects. Tocotrienol also prevented multiple systemic complications due to obesity and diabetes in animal models through suppression of inflammation and oxidative stress. Several clinical trials have been conducted to validate the antidiabetic of tocotrienol, but the results were heterogeneous. There is no evidence showing the anti-obesity effects of tocotrienol in humans. Considering the limitations of the current studies, tocotrienol has the potential to be a functional food component to aid in the management of patients with obesity and diabetes.
    Matched MeSH terms: Tocotrienols/pharmacology; Tocotrienols/chemistry*
  12. Fulltext The Effect of Pressure and Solvent on the Supercritical Fluid Chromatography Separation of Tocol Analogs in Palm Oil
    Ng MH, Kushairi A
    Molecules, 2017 Aug 29;22(9).
    PMID: 28850073 DOI: 10.3390/molecules22091424
    There are six tocol analogs present in palm oil, namely α-tocopherol (α-T), α-tocomonoenol (α-T₁), α-tocotrienol (α-T₃), γ-tocotrienol (γ-T₃), β-tocotrioenol (β-T₃) and δ-tocotrienol (δ-T₃). These analogs were difficult to separate chromatographically due to their similar structures, physical and chemical properties. This paper reports on the effect of pressure and injection solvent on the separation of the tocol analogs in palm oil. Supercritical CO₂ modified with ethanol was used as the mobile phase. Both total elution time and resolution of the tocol analogs decreased with increased pressure. Ethanol as an injection solvent resulted in peak broadening of the analogs within the entire pressure range studied. Solvents with an eluent strength of 3.4 or less were more suitable for use as injecting solvents.
    Matched MeSH terms: Tocotrienols/isolation & purification; Tocotrienols/chemistry
  13. Fulltext Chromatographic Separation of Vitamin E Enantiomers
    Fu JY, Htar TT, De Silva L, Tan DM, Chuah LH
    Molecules, 2017 Feb 04;22(2).
    PMID: 28165404 DOI: 10.3390/molecules22020233
    Vitamin E is recognized as an essential vitamin since its discovery in 1922. Most vegetable oils contain a mixture of tocopherols and tocotrienols in the vitamin E composition. Structurally, tocopherols and tocotrienols share a similar chromanol ring and a side chain at the C-2 position. Owing to the three chiral centers in tocopherols, they can appear as eight different stereoisomers. Plant sources of tocopherol are naturally occurring in the form of RRR while synthetic tocopherols are usually in the form of all-racemic mixture. Similarly, with only one chiral center, natural tocotrienols occur as the R-isoform. In this review, we aim to discuss a few chromatographic methods that had been used to separate the stereoisomers of tocopherols and tocotrienols. These methods include high performance liquid chromatography, gas chromatography and combination of both. The review will focus on method development including selection of chiral columns, detection method and choice of elution solvent in the context of separation efficiency, resolution and chiral purity. The applications for separation of enantiomers in vitamin E will also be discussed especially in terms of the distinctive biological potency among the stereoisoforms.
    Matched MeSH terms: Tocotrienols/chemistry
  14. Effects of topically applied tocotrienol on cataractogenesis and lens redox status in galactosemic rats
    Abdul Nasir NA, Agarwal R, Vasudevan S, Tripathy M, Alyautdin R, Ismail NM
    Mol Vis, 2014;20:822-35.
    PMID: 24940038
    Oxidative and nitrosative stress underlies cataractogenesis, and therefore, various antioxidants have been investigated for anticataract properties. Several vitamin E analogs have also been studied for anticataract effects due to their antioxidant properties; however, the anticataract properties of tocotrienols have not been investigated. In this study, we investigated the effects of topically applied tocotrienol on the onset and progression of cataract and lenticular oxidative and nitrosative stress in galactosemic rats.
    Matched MeSH terms: Tocotrienols/administration & dosage*; Tocotrienols/pharmacology; Tocotrienols/therapeutic use*
  15. δ- and γ-tocotrienols induce classical ultrastructural apoptotic changes in human T lymphoblastic leukemic cells
    Wong RS, Radhakrishnan AK, Ibrahim TA, Cheong SK
    Microsc Microanal, 2012 Jun;18(3):462-9.
    PMID: 22640960 DOI: 10.1017/S1431927612000177
    Tocotrienols are isomers of the vitamin E family, which have been reported to exert cytotoxic effects in various cancer cells. Although there have been some reports on the effects of tocotrienols in leukemic cells, ultrastructural evidence of tocotrienol-induced apoptotic cell death in leukemic cells is lacking. The present study investigated the effects of three isomers of tocotrienols (alpha, delta, and gamma) on a human T lymphoblastic leukemic cell line (CEM-SS). Cell viability assays showed that all three isomers had cytotoxic effects (p < 0.05) on CEM-SS cells with delta-tocotrienol being the most potent. Transmission electron microscopy showed that the cytotoxic effects by delta- and gamma-tocotrienols were through the induction of an apoptotic pathway as demonstrated by the classical ultrastructural apoptotic changes characterized by peripheral nuclear chromatin condensation and nuclear fragmentation. These findings were confirmed biochemically by the demonstration of phosphatidylserine externalization via flow cytometry analysis. This is the first study showing classical ultrastructural apoptotic changes induced by delta- and gamma-tocotrienols in human T lymphoblastic leukemic cells.
    Matched MeSH terms: Tocotrienols
  16. Analysis of tocotrienols in different sample matrixes by HPLC
    Sundram K, Nor RM
    Methods Mol Biol, 2002;186:221-32.
    PMID: 12013770
    Matched MeSH terms: Tocotrienols/analysis*; Tocotrienols/blood
  17. Fulltext Effects of Palm Tocotrienols on Oxidative Stress and Bone Strength in Ovariectomised Rats
    Nazrun, A.S., Khairunnur, A., Norliza, M., Norazlina, M., Iman Nirwana, S.
    Medicine & Health, 2008;3(2):247-255.
    MyJurnal
    Oxidative stress has been associated with postmenopausal osteoporosis which pre-disposes to risk of fracture. Palm tocotrienol is a potent antioxidant and has the poten-tial to be used for treatment of post-menopausal osteoporosis. The aim of the study is to determine if palm tocotrienol supplementation could alleviate oxidative stress in ovariectomised rat model and improve its bone strength. The rats were di- vided into four groups: (i) sham-operated  group (SHAM) (ii) ovariectomised-control group (OVX) (iii) ovariectomised and given 60mg/kg α-tocopherol by oral gavage (OVX + ATF) (iv) ovariectomised and given 60mg/kg palm tocotrienols by oral gavage (OVX + PTT). After eight weeks of treatment, blood samples were taken to measure oxida-tive status (MDA, SOD and GPX) while the femurs were biomechanically tested for strength and resistance to fracture. Ovariectomy was shown to induce oxidative stress as shown by the raised MDA levels and reduced GPX activity. Palm tocotrienols seemed to offer protection against the ovariectomy-induced oxidative stress as shown by the suppression of MDA levels and raised GPX and SOD activities in the OVX+PTT group. In comparison, α-tocopherol was only able to raise the SOD but not as high as palm tocotrienols. The biomechanical tests have shown that ovariectomy has not af-fected the bone strength significantly after eight weeks. Palm tocotrienols supplemen-tation for eight weeks was effective in preventing oxidative stress in a post-meno-pausal rat.
    Matched MeSH terms: Tocotrienols
  18. Effects of Nicotine and Tocotrienol-Rich Fraction Supplementation on Cytoskeletal Structures of Murine Pre-Implantation Embryos
    Hamirah NK, Kamsani YS, Mohamed Nor Khan NA, Ab Rahim S, Rajikin MH
    Med Sci Monit Basic Res, 2017 Dec 08;23:373-379.
    PMID: 29217815
    BACKGROUND Cytoskeletal structures, in particular actin and tubulin, provide a fundamental framework in all cells, including embryos. The objective of this study was to evaluate the effects of nicotine, which is a source of oxidative stress, and subsequent supplementation with Tocotrienol-rich fraction (TRF) on actin and tubulin of 2- and 8-cell murine embryos. MATERIAL AND METHODS Thirty female Balb/C mice were divided into 4 groups: Group 1 received: subcutaneous (sc) injection of 0.9% NaCl; Group 2 received sc injection of 3.0 nicotine mg/kg bw/day; Group 3 received 3.0 sc injection of nicotine mg/kg bw/day +60 mg/kg bw/day TRF; and Group 4 received 60 sc injection of TRF mg/kg bw/day for 7 consecutive days. The animals were superovulated with 5 IU PMSG followed by 5 IU hCG 48 h later. Animals were cohabited with fertile males overnight and euthanized through cervical dislocation at 24 h post coitum. Embryos at the 2- and 8-cell stages were harvested, fixed, and stained to visualize actin and tubulin distributions by using CLSM. RESULTS Results showed that at 2-cell stage, actin intensities were significantly reduced in the nicotine group compared to that of the control group (p<0.001). In Group 3, the intensity of actin significantly increased compared to that of the nicotine group (p<0.001). At 8-cell stage, actin intensity of the nicotine group was significantly lower than that of the control group (p<0.001). The intensities of actin in Group 3 were increased compared to that of nicotine treatment alone (p<0.001). The same trend was seen in tubulin at 2- and 8-cell stages. Interestingly, both actin and tubulin structures in the TRF-treated groups were enhanced compared to the control. CONCLUSIONS This study suggests that TRF prevents the deleterious effects of nicotine on the cytoskeletal structures of 2- and 8-cell stages of pre-implantation mice embryos in vitro.
    Matched MeSH terms: Tocotrienols/metabolism*
  19. Fulltext Selective uptake of alpha-tocotrienol and improvement in oxidative status in rat brains following short- and long- term intake of tocotrienol rich fraction
    Musalmah, M., Leow, K.S., Nursiati, M.T., Raja Najmi Hanis Raja, l., Fadly Syah, A., Renuka, S., et al.
    Malays J Nutr, 2013;19(2):251-259.
    MyJurnal
    Introduction: Tocotrienol exerts neuroprotective effects resulting in an improved circulating oxidative status. However, accumulation of tocotrienol due to longterm intake may exert pro-oxidant effects. Thus the effects of short- and longterm supplementation of vitamin E tocotrienol rich fraction (TRF) on the parameters of oxidative status in rat brains were determined. Methods: Wistar rats aged 3 months were supplemented with TRF for 3 or 8 months. Control groups received equivolume of distilled water. Rats were sacrificed and brains
    harvested, weighed and homogenised. Supernatants were analysed for catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities, vitamin E and protein carbonyl. Results: A significant decline in the level of total vitamin E and its isomers with increasing age were found. TRF supplementation increased the level of total vitamin E with alpha-tocotrienol (ATT) being the major isomer raised. Glutathione peroxidase activity was also
    significantly increased in the long-term supplemented group compared to the short-term supplemented and control groups. The results also showed significantly higher superoxide dismutase activity (p
    Matched MeSH terms: Tocotrienols
  20. Fulltext Dose-dependent cholesterolemic activity of tocotrienols and α-tocopherol
    Khor, Hun Teik, Ng, Theng Theng, Rajendran, Raajeswari
    Malays J Nutr, 2002;8(2):157-166.
    MyJurnal
    Tocotrienols and tocopherols are isoforms of vitamin E. Vitamin E may exhibit antioxidant, prooxidant and non-antioxidant activities depending upon circumstances. In this study, the effect of tocotrienols and α-tocopherol on the activities of HMG CoA reductase and cholesterol 7 α-hydroxylase was investigated. Pure tocotrienols were isolated from palm fatty acid distillate and pure α-tocopherol was obtained commercially. Guinea pigs were treated with different dosages of tocotrienols and α-tocopherol. After the treatment period, animals were sacrificed and liver microsomes were prepared. HMG CoA reductase and cholesterol 7α-hydroxylase were assayed using tracer techniques. Our results showed that the effects of tocotrienols and α-tocopherol on the activities of both the enzymes were dose-dependent. At low dosages, both tocotrienols and α-tocopherol exhibited an inhibitory effect on both the enzymes. Moreover, tocotrienols were a much stronger inhibitors than α-tocopherol. At high dosages, on the other hand, tocotrienols and α-tocopherol showed opposite effects on the enzymes. While tocotrienols continued to exhibit an inhibitory effect, α-tocopherol actually exhibited a stimulatory effect on both the enzymes. A possible explanation for this observation is suggested.
    Matched MeSH terms: Tocotrienols
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