The oil palm tree, Elaeis guineesis, is the source of palm oil, otherwise known as the “tropical golden oil”. To date, Malaysia and Indonesia are the leading producers of palm oil. Palm oil is widely used for domestic cooking in Malaysia. Palm oil is a rich source of phytonutrients such astocotrienols, tocopherol, carotene, phytosterols, squalene, coenzyme Q10, polyphenols, and phospholipids. Although the phytonutrients constitute only about 1% of its weight in crude palm oil, these are the main constituents through which palm oil exhibits its nutritional properties. Among the major health promoting properties shown to be associated with the various types of phytonutrients present in palm oil are anti-cancer, cardio-protection and anti-angiogenesis, cholesterol inhibition, brain development and neuro protective properties, antioxidative defence mechanisms, provitamin A activity and anti-diabetes.

To determine the bioavailability of tocotrienol complex with gamma-cyclodextrin, the effects of tocotrienol/gamma-cyclodextrin complex on tocotrienol concentration in rat plasma and tissues were studied. Rats were administered by oral gavage an emulsion containing tocotrienol, tocotrienol with gamma-cyclodextrin, or tocotrienol/gamma-cyclodextrin complex. At 3 h after administration, the plasma gamma-tocotrienol concentration of the rats administered tocotrienol/gamma-cyclodextrin complex was higher than that of the rats administered tocotrienol and gamma-cyclodextrin. In order to determine the effect of complexation on tocotrienol absorption, rats were injected with Triton WR1339, which prevents the catabolism of triacylglycerol-rich lipoprotein by lipoprotein lipase, and then administered by oral gavage an emulsion containing tocotrienol, tocotrienol with gamma-cyclodextrin, or tocotrienol/gamma-cyclodextrin complex. The plasma gamma-tocotrienol concentration of the Triton-treated rats administered tocotrienol/gamma-cyclodextrin complex was higher than that of the other Triton-treated rats. These results suggest that complexation of tocotrienol with gamma-cyclodextrin elevates plasma and tissue tocotrienol concentrations by enhancing intestinal absorption.

INTRODUCTION: Vitamin E is beneficial in restoring bone histomorphometric parameters in nicotine-treated rats. This study determined the effectiveness of 3 forms of vitamin E in restoring bone metabolism in nicotine-treated rats.

MATERIAL AND METHODS: Thirty-five male Sprague-Dawley rats were divided into 5 groups: (1) control (C), (2) nicotine cessation (NC), (3) α-tocopherol (ATF), (4) tocotrienol-enhanced fraction (TEF) and (5) γ-tocotrienol (GTT). Treatment was carried out for 4 months. The control group was administered normal saline and olive oil throughout the treatment period while treatment for groups 2-5 was performed in 2 phases. In the first phase, the groups received nicotine 7 mg/kg intraperitoneally for 2 months. The following 2 months, group 2 received normal saline and olive oil while groups 3-5 received ATF, TEF or GTT, 60 mg/kg orally. Pre-treatment and post-treatment serum was collected for bone biochemical marker measurement using the ELISA method.

RESULTS: Nicotine increased serum bone-resorbing cytokines (interleukin-1 and interleukin-6) and the bone resorption marker pyridinoline (PYD) while reducing the bone formation marker osteocalcin after 2 months of nicotine treatment. The parameters failed to improve after nicotine was stopped for 2 months. Supplementation with the 3 forms of vitamin E improved the parameters, i.e. reduced the cytokines and pyridinoline as well as increased the osteocalcin. In addition, the TEF and GTT groups had a higher level of osteocalcin than the control group.

CONCLUSIONS: Nicotine impaired bone metabolism and cessation of nicotine treatment did not reverse the effects. Vitamin E, especially the tocotrienols, restored bone metabolism that was impaired due to nicotine.

Industrial and occupational exposure to chromium compounds, particularly hexavalent chromium (Cr(VI))-containing compounds are often known to cause acute renal injury (ARI) in humans and animals. Its nephrotoxicity is associated with an increased formation of reactive oxygen species and lipid peroxidation in renal tissue. Recent studies suggest that antioxidants of the vitamin E family have protective effects against metal toxicity.Tocotrienols are known to have greater antioxidant activity than tocopherols and protect more efficiently against some free radical-related diseases than does tocopherols. In the present study, ARI induced by potassium dichromate (K(2)Cr(2)O(7)) has been used as a model to investigate the possible nephroprotective effect of tocotrienol-rich fraction (TRF) from palm oil. Wistar male rats having an average body weight (bw) of 210 g were divided into four groups. The first group was taken as control and injected with vehicle alone while the second group was drug control and ingested with TRF (200mg/kg, bw, orally, once daily for 21 days); the third group served as toxicant and was pre-treated with saline, followed by a single subcutaneous (SC) injection of K(2)Cr(2)O(7) (15 mg/kg bw). The fourth group was pre-treated with TRF and subsequently injected with K(2)Cr(2)O(7) (same dose as for the third group). Renal functions, oxidative and nitrosative stress were evaluated on days 0, 1, 2, 4, 7, 11 and 14 after treatment with K(2)Cr(2)O(7). The results revealed altered proximal tubular function; decreased glomerular filtration accompanied by oxidative damage 48 h after exposure to dichromate; while in the TRF-treated group proximal reabsorptive function, glomerular function and the cellular redox status were sustained. These results were further supported and confirmed by histological findings. The study suggests that TRF is effective in preventing K(2)Cr(2)O(7)-induced acute renal injury, but more studies are needed to confirm the effects of TRF as a nephroprotective agent.

To determine the bioavailability of tocotrienol complex with gamma-cyclodextrin, the effects of tocotrienol/gamma-cyclodextrin complex ontocotrienol concentration in rat plasma and tissues were studied. Rats were administered by oral gavage an emulsion containing tocotrienol,tocotrienol with gamma-cyclodextrin, or tocotrienol/gamma-cyclodextrin complex. At 3 h after administration, the plasma gamma-tocotrienolconcentration of the rats administered tocotrienol/gamma-cyclodextrin complex was higher than that of the rats administered tocotrienol and gamma-cyclodextrin. In order to determine the effect of complexation on tocotrienol absorption, rats were injected with Triton WR1339, which prevents the catabolism of triacylglycerol-rich lipoprotein by lipoprotein lipase, and then administered by oral gavage an emulsion containing tocotrienol,tocotrienol with gamma-cyclodextrin, or tocotrienol/gamma-cyclodextrin complex. The plasma gamma-tocotrienol concentration of the Triton-treated rats administered tocotrienol/gamma-cyclodextrin complex was higher than that of the other Triton-treated rats. These results suggest that complexation of tocotrienol with gamma-cyclodextrin elevates plasma and tissue tocotrienol concentrations by enhancing intestinal absorption.

α-Tocopherol (a-Toc) enhances T cell function, whereas little is known in this regard for tocotrienols (T3), the less-known members of the vitamin E family. We pair-fed young (4 mo) and old (23 mo) C57BL/6 mice 0.1% Tocomin 50%, a mixture of T3 and α-Toc or a control diet containing an equal amount of α-Toc for 6 wk. As expected, lymphocyte proliferation was lower in the old mice compared with the young mice. Lymphocyte proliferation in the old T3 group was significantly higher than that in the old control group, whereas no significant difference was found in young mice. Splenocytes from old mice produced less interleukin (IL)-2, IL-4, IL-6, and IL-10 compared with young mice, whereas no significant age-related difference was found in IL-1b, tumor necrosis factor-a, and interferon-g. T3 feeding was associated with a higher IL-1b production in old mice but not in young mice. Peritoneal macrophages from old mice produced significantly more IL-1b, IL-6, IL-10, and prostaglandin E2 (PGE2) compared with those from young mice. Mice of both ages fed T3 had higher production of IL-1b but not PGE2 or other cytokines. In the in vitro study, splenocytes isolated from young and old mice were supplemented with the purified form of each individual T3 (0.01–10 mmol/L) and mitogen-stimulated cell proliferation was determined. All T3 enhanced lymphocyte proliferation in old but not young mice with a potency order of α> γ> δ-T3. Together, these results suggest a beneficial effect of T3 in improving the age-related decline in T cell function.

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Nanostructured lipid carriers (NLCs), made from mixtures of solid and liquid lipids, were postulated to have superior properties over solid lipid nanoparticles (SLNs). Nonetheless, the architecture of their inner cores remains elusive. The objective of this study was to elucidate the mode by which tocotrienol-rich fraction (TRF) is entrapped within NLCs and the impact of TRF interaction with solid lipids on the long-term stability of the nanoparticles. The mode of TRF localization was postulated from TEM image analysis and (1)H NMR signals’ amplitude. The size, polydispersity, and fusion enthalpy were found to decrease with an increase in TRF loading, which implied a distortion in the crystallinity of the nanoparticles and the preferential entrapment of TRF within the cores of the NLCs. Nonetheless, (1)H NMR spectra of TRF-NLCs broadened as TRF load decreased from 100 to 10%, which was attributed to partial TRF mobility on the surface of the nanoparticles. This was confirmed by TEM images of NLCs at 50% TRF loads. These data led to the conclusion that NLCs have limited capacity to accommodate TRF with the excess being expelled to the surface of the nanoparticles. Such arrangement may have implication on future utility of the NLCs as drug delivery vehicles.

gamma-Tocotrienol (gamma-T3) is a member of the vitamin E family that displays potent anticancer activity and other therapeutic benefits. The objective of this study was to evaluate gamma-T3 intestinal uptake and metabolism using the in situ rat intestinal perfusion model. Isolated segments of rat jejunum and ileum were perfused with gamma-T3 solution, and measurements were made as a function of concentration (5-150 microM). Intestinal permeability (P(eff)) and metabolism were studied by measuring total compound disappearance and major metabolite, 2,7,8-trimethyl-2-(beta-carboxy-ethyl)-6-hydroxychroman, appearance in the intestinal lumen. gamma-T3 and metabolite levels were also determined in mesenteric blood. The P(eff) of gamma-T3 was similar in both intestinal segments and significantly decreased at concentrations > or =25 microM in jejunum and ileum (p < 0.05), whereas metabolite formation was minimal and mesenteric blood concentrations of gamma-T3 and metabolite remained very low. These results indicate that gamma-T3 intestinal uptake is a saturable carrier-mediated process and metabolism is minimal. Results from subsequent in situ inhibition studies with ezetimibe, a potent and selective inhibitor of Niemann-Pick C1-like 1 (NPC1L1) transporter, suggested gamma-T3 intestinal uptake is mediated by NPC1L1. Comparable findings were obtained when Madin-Darby canine kidney II cells that express endogenous NPC1L1 were incubated with increasing concentrations of gamma-T3 or gamma-T3 with increasing concentrations of ezetimibe. The present data show for the first time that gamma-T3 intestinal absorption is partly mediated by NPC1L1.

Tocopherols and tocotrienols have been originally identified as essential nutrients in mammals based on their vitamin E activity. These lipid-soluble compounds are potent antioxidants that protect polyunsaturated fatty acids from lipid peroxidation. The biosynthesis of tocopherols and tocotrienolsoccurs exclusively in photosynthetic organisms. The biosynthetic precursors and the different pathway intermediates have been identified by biochemical studies and the different vitamin E biosynthetic genes (VTE genes) have been isolated in several plants and cyanobacteria. The characterization of transgenic plants overexpressing one or multiple VTE genes combined with the study of vitamin E deficient mutants allows from now on understanding the regulation and the function of tocopherols and tocotrienols in plants.

Vitamin E is composed of closely related compounds, including tocopherols and tocotrienols. Studies of the last decade provide strong support for a specific role of alpha-tocopherol in cell signalling and the regulation of gene expression. It produces significant effects on inflammation, cell proliferation and apoptosis that are not shared by other vitamin E isomers with similar antioxidant properties. The different behaviours of vitamin E isomers might relate, at least in part, to the specific effects they exert at the plasma membrane. alpha-Tocopherol is not randomly distributed throughout the phospholipid bilayer of biological membranes, and as compared with other isomers, it shows a propensity to associate with lipid rafts. Distinct aspects of vitamin E transport and metabolism is discussed with emphasis on the interaction between alpha-tocopherol and lipid rafts and the consequences of these interactions on cell metabolism.