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Dose-response impact of various tocotrienols on serum lipid parameters in 5-week-old female chickens.
Yu SG, Thomas AM, Gapor A, Tan B, Qureshi N, Qureshi AA.
Advanced Medical Research, Madison, Wisconsin 53719, USA.
The cholesterol-suppressive action of the tocotrienol-rich-fraction (TRF) of palm oil may be due to the effect of its constituent tocotrienols on beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase activity. The tocotrienols, modulate HMG-CoA reductase activity via a post-transcriptional mechanism. As a consequence small doses (5-200 ppm) of TRF-supplemented diets fed to experimental animals lower serum cholesterol levels. These findings led us to evaluate the safety and efficacy of large supplements of TRF and its constituents. Diets supplemented with 50, 100, 250, 500, 1000, or 2000 ppm of TRF, alpha-tocopherol, alpha-tocotrienol, gamma-tocotrienol, or 6-tocotrienol were fed to chickens for 4 wk. There were no differences between groups or within groups in weight gain, or in feed consumption at the termination of the feeding period. Supplemental TRF produced a dose-response (50-2000 ppm) lowering of serum total and LDL cholesterol levels of 22% and 52% (P < 0.05), respectively, compared with the control group. alpha-Tocopherol did not affect total or LDL-cholesterol levels. Supplemental alpha-tocotrienol within the 50-500 ppm range produced a dose-response lowering of total (17%) and LDL (33%) cholesterol levels. The more potent gamma and delta isomers yielded dose-response (50-2,000 ppm) reductions of serum total (32%) and LDL (66%) cholesterol levels. HDL cholesterol levels were minimally impacted by the tocotrienols; as a result, the HDL/LDL cholesterol ratios were markedly improved (123-150%) by the supplements. Serum triglyceride levels were significantly lower in sera of pullets receiving the higher supplements. The safe dose of various tocotrienols for human consumption might be 200-1000 mg/d based on this study.
PMID: 16933790 [PubMed - indexed for MEDLINE]
Proposed mechanisms for red palm oil induced cardioprotection in a model of hyperlipidaemia in the rat.
Esterhuyse JS, van Rooyen J, Strijdom H, Bester D, du Toit EF.
Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa; Department of Physiological Sciences, University of Stellenbosch, South Africa.
High-cholesterol diets alter myocardial and vascular NO-cGMP signaling and have been implicated in ischaemic/reperfusion injury. We investigated the effects of dietary red palm oil (RPO) containing fatty acids, carotonoids, tocopherols and tocotrienols on myocardial ischaemic tolerance and NO-cGMP pathway function in the rat. Wistar rats were fed a standard rat chow+/-RPO, or a standard rat chow+cholesterol+/-RPO diet. Myocardial mechanical function and NO-cGMP signaling pathway intermediates were determined before, during and after 25min ischaemia. RPO-supplementation improved aortic output recovery and increased myocardial ischaemic cGMP concentrations. Simulated ischaemia (hypoxia) increased cardiomyocyte nitric oxide levels in the two RPO supplemented groups, but not in control non-supplemented groups. RPO supplementation also increased hypoxic nitric oxide levels in the control diet fed, but not the cholesterol fed rats. These data suggest that dietary RPO may improve myocardial ischaemic tolerance by increasing bioavailability of NO and improving NO-cGMP signaling in the heart.
PMID: 16920346 [PubMed - in process]
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Tocotrienol-rich fraction of palm oil induces cell cycle arrest and apoptosis selectively in human prostate cancer cells.
Srivastava JK, Gupta S.
Department of Urology, Case Western Reserve University, Cleveland, OH 44106, USA.
One of the requisite of cancer chemopreventive agent is elimination of damaged or malignant cells through cell cycle inhibition or induction of apoptosis without affecting normal cells. In this study, employing normal human prostate epithelial cells (PrEC), virally transformed normal human prostate epithelial cells (PZ-HPV-7), and human prostate cancer cells (LNCaP, DU145, and PC-3), we evaluated the growth-inhibitory and apoptotic effects of tocotrienol-rich fraction (TRF) extracted from palm oil. TRF treatment to PrEC and PZ-HPV-7 resulted in almost identical growth-inhibitory responses of low magnitude. In sharp contrast, TRF treatment resulted in significant decreases in cell viability and colony formation in all three prostate cancer cell lines. The IC(50) values after 24h TRF treatment in LNCaP, PC-3, and DU145 cells were in the order 16.5, 17.5, and 22.0 microg/ml. TRF treatment resulted in significant apoptosis in all the cell lines as evident from (i) DNA fragmentation, (ii) fluorescence microscopy, and (iii) cell death detection ELISA, whereas the PrEC and PZ-HPV-7 cells did not undergo apoptosis, but showed modestly decreased cell viability only at a high dose of 80 microg/ml. In cell cycle analysis, TRF (10-40 microg/ml) resulted in a dose-dependent G0/G1 phase arrest and sub G1 accumulation in all three cancer cell lines but not in PZ-HPV-7 cells. These results suggest that the palm oil derivative TRF is capable of selectively inhibiting cellular proliferation and accelerating apoptotic events in prostate cancer cells. TRF offers significant promise as a chemopreventive and/or therapeutic agent against prostate cancer.
PMID: 16762318 [PubMed - indexed for MEDLINE]
Molecular mechanism of antioxidant synergism of tocotrienols and carotenoids in palm oil.
Schroeder MT, Becker EM, Skibsted LH.
Department of Food Science, Food Chemistry, The Royal Veterinary and Agricultural University, Rolighedsvej 30, DK-1958 Frederiksberg C, Denmark.
During repeated deep-fat frying of potato slices at 163 degrees C in yellow or red palm olein of comparable fatty acid profiles, the oxidative stability (peroxide value and anisidine value) of the palm oleins was similar, and in yellow palm olein, the rate of antioxidant depletion decreased in the order gamma-T3 > alpha-T3 > delta-T3 (T3, tocotrienol). In red palm olein, which had a total tocopherol/tocotrienol content of 1260 vs 940 ppm in yellow palm olein and a corresponding longer induction period in the Rancimat stability test at 120 degrees C, only depletion of gamma-T3 was significant among the phenols during frying and slower as compared to that in yellow palm olein. The carotenes in the red palm olein were depleted linearly with the number of fryings, apparently yielding an overall protection of the phenols. In antioxidant-depleted palm olein and in phospholipid liposomes with added increasing concentrations of phenols, gamma-T3 was found to be a better antioxidant than alpha-T3. alpha-T3 and alpha-T (T, tocopherol) had a similar antioxidant effect in antioxidant-depleted palm olein in the Rancimat stability test, while in the liposomes the ordering as determined by induction period for the formation of conjugated dienes was gamma-T3 > alpha-T3 > alpha-T. The addition of 100-1000 ppm beta-carotene to antioxidant-depleted palm olein or liposomes (lycopene also tested) did not provide any protection against oxidation. In the liposomes, synergistic interactions were observed between beta-carotene or lycopene and alpha-T, alpha-T3, or gamma-T3 for carotene/phenol ratios of 1:10 and 1:2 but not for 1:1. In chloroform, carotenes were regenerated by tocopherols/tocotrienols from carotene radicals generated by laser flash photolysis as shown by transient absorption spectroscopy, suggesting that carotenes rather than phenols are the primary substrate for lipid-derived radicals in red palm olein, in effect depleting carotenes prior to phenols during frying. Regeneration of carotenes by the phenols also explains the synergism in liposomes. In the laser flash photolysis experiments, gamma-T3 was also found to be faster in regenerating carotenes than alpha-T3 and alpha-T.
PMID: 16637706 [PubMed - indexed for MEDLINE]
Palm oil and palm olein frying applications.
Ismail R.
Malaysian Palm Oil Board, No. 6, Persiaran Institusi, Bandar Baru Bangi, 43000 Kajang, Selangor, Malaysia. razali@mpob.gov.my
Several million tones of palm oil and palm olein are used annually in the world for frying. This paper will discuss their frying performances in three major applications - industrial production of potato chips/crisps, industrial production of pre-fried frozen French fries and in fast food outlets. In the first study, about four tones of potato chips were continuously fried 8 hours a day and five days a week. The palm olein used (with proper management) performed well and was still in excellent condition and usable at the end of the trial. This was reflected in its low free fatty acid (FFA) content of around 0.23%, peroxide value of 4 meq/kg, anisidine value of 16, low polar and polymer contents of 10% and 2%, respectively, induction period (OSI) of 21 hours and high content of tocopehrols and tocotrienols of 530 ppm even after >1900 hours. In the second study in which an average 12 tones pre-fried frozen French fries were continuously fried a day for 5 days a week, palm oil performed excellently as reflected by its low FFA of 0.34%, food oil sensor reading of 1.1, low polar and polymer contents of 17% and 2.8%, respectively, over the 12 days of trial. In the third study in which palm shortening, palm oil and palm olein were simultaneously used to intermittently fry chicken parts in the laboratory simulating the conditions in fast food outlets, the three frying oils also performed very satisfactorily as reflected by their reasonably low FFA of <1%, smoke points of >180 degrees C, and polar and polymer contents of <25% and <6%, respectively, after 5 days of consecutive frying. All the quality indicators did not exceed the maximum discard points for frying oils/fats in the three applications, while the fried food product was well accepted by the in-house train sensory panel using a-nine point hedonic score.
PMID: 16326649 [PubMed - indexed for MEDLINE]
Dietary red palm oil supplementation protects against the consequences of global ischemia in the isolated perfused rat heart.
Esterhuyse AJ, Toit ED, Rooyen JV.
Faculty of Applied Sciences, PO Box 652,Cape Peninsula University of Technology, Cape Town, South Africa. esterhuysejs@cput.ac.za
Activation of the NO-cGMP pathway is associated with myocardial protection against ischemia. During ischemia, function of this pathway is disturbed. Little is known about the effects of supplements such as Red Palm Oil (RPO) on the myocardial NO- cGMP- signalling pathway. RPO consists of saturated (SFAs), mono-unsaturated (MUFAs) and polyunsaturated (PUFAs) fatty acids and is an antioxidant rich in natural B-carotene and vitamin E (tocopherols and tocotrienols). This study determined whether dietary RPO-supplementation protects against the consequences of ischemia and identified a possible mechanism for this protection. Long-Evans rats were fed a control diet or control diet plus 7 g RPO per kg diet for six weeks. Hearts were excised and mounted on a working heart perfusion apparatus. Cardiac function was measured before and after hearts were subjected to 25 minutes of global ischemia. Left ventricular systolic (LVSP) and diastolic pressure (LVDP), coronary flow (CF), heart rate (HR) and aortic output (AO) were measured. To assess NO-cGMP pathway activity, hearts subjected to the same conditions, were freeze-clamped and analysed for tissue cAMP and cGMP levels using a RIA method. Furthermore, composition of myocardial phospholipid fatty acids by gas chromatography and blood samples were collected for serum lipid determinations. The percentage aortic output recovery of hearts supplemented with RPO was 72.9 +/-3.43% vs 55.4 +/-2.48% for controls (P< 0.05). Ten minutes into ischemia the cGMP levels of the RPO-supplementation group were significantly higher than the control group (26.5+/-2.78 pmol/g vs 10.1+/-1.78 pmol/g. Total myocardial PUFA content in hearts supplemented with RPO increased from 54.45+/-1.11% before ischemia to 59.03 +/- 0.30% after ischemia P<0.05). Results demonstrated that RPO-supplementation protected hearts against the consequences of ischemia/reperfusion injury. These findings suggest that dietary RPO protects via the NO-cGMP pathway and/or changes in PUFA composition during ischemia/reperfusion.
PMID: 16326640 [PubMed - indexed for MEDLINE]
Tocotrienol offers better protection than tocopherol from free radical-induced damage of rat bone.
Ahmad NS, Khalid BA, Luke DA, Ima Nirwana S.
Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia.
1. Free radicals generated by ferric nitrilotriacetate (FeNTA) can activate osteoclastic activity and this is associated with elevation of the bone resorbing cytokines interleukin (IL)-1 and IL-6. In the present study, we investigated the effects of 2 mg/kg FeNTA (2 mg iron/kg) on the levels of serum IL-1 and IL-6 with or without supplementation with a palm oil tocotrienol mixture or alpha-tocopherol acetate in Wistar rats. 2. The FeNTA was found to elevate levels of IL-1 and IL-6. Only the palm oil tocotrienol mixture at doses of 60 and 100 mg/kg was able to prevent FeNTA-induced increases in IL-1 (P < 0.01). Both the palm oil tocotrienol mixture and alpha-tocopherol acetate, at doses of 30, 60 and 100 mg/kg, were able to reduce FeNTA-induced increases in IL-6 (P < 0.05). Therefore, the palm oil tocotrienol mixture was better than pure alpha-tocopherol acetate in protecting bone against FeNTA (free radical)-induced elevation of bone-resorbing cytokines. 3. Supplementation with the palm oil tocotrienol mixture or alpha-tocopherol acetate at 100 mg/kg restored the reduction in serum osteocalcin levels due to ageing, as seen in the saline (control) group (P < 0.05). All doses of the palm oil tocotrienol mixture decreased urine deoxypyridinoline cross-link (DPD) significantly compared with the control group, whereas a trend for decreased urine DPD was only seen for doses of 60 mg/kg onwards of alpha-tocopherol acetate (P < 0.05). 4. Bone histomorphometric analyses have shown that FeNTA injections significantly lowered mean osteoblast number (P < 0.001) and the bone formation rate (P < 0.001), but raised osteoclast number (P < 0.05) and the ratio of eroded surface/bone surface (P < 0.001) compared with the saline (control) group. Supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent all these FeNTA-induced changes, but a similar dose of alpha-tocopherol acetate was found to be effective only for mean osteoclast number. Injections of FeNTA were also shown to reduce trabecular bone volume (P < 0.001) and trabecular thickness (P < 0.05), whereas only supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent these FeNTA-induced changes.
PMID: 16173934 [PubMed - indexed for MEDLINE]
[Effects of vegetal oil supplementation on the lipid profile of Wistar rats ]
[Article in Spanish]
Poveda E, Ayala P, Milena R, Ordonez E, Baracaldo C, Delgado W, Guerra M.
Grupo de Nutricion, Subdireccion de Investigacion, Instituto Nacional de Salud, Bogota, D.C., Colombia. epoveda@ins.gov.co
BACKGROUND: Dietary tocopherols, tocotrienols and saturated, mono and polyunsaturated fatty acids have been reported to have an effect on blood lipid profiles. In Colombia, vegetable oils (palm, soy, corn, sunflower, and canola) are a common dietary constituent and consumed in high quantities. OBJECTIVE: In the current study, the effects of vegetable oil consumption was examined by measuring blood concentrations of triglycerides (TG), total cholesterol (TC) and HDL cholesterol (HDL-C) in male Wistar rats. METHODS: The concentrations of tocopherols, tocotrienols, and fatty acids in each oil was quantified by High Performance Liquid Chromatography (HPLC). Each rat diet was supplemented with 0.2 ml/day with one oil type. Over a 4-week period, groups of animals were sacrificed weekly and blood samples were obtained to quantify TC, TG and HDL-C for each oil class. Statistical analyses included mean, standard deviation, ANOVA and Bonferroni comparisons tests. RESULTS: Triglyceride content was not affected except in the control and the soy group in the third treatment week, although a tendency for decreased TG was noted in the palm oil group and for increased TG in the sunflower oil and canola oil groups. No significant differences in total cholesterol were observed. In HDL-C, significant differences were present for every treatment week (p = 0.005); this represented a decreasing trend in palm oil group and an increasing trend in the sunflower and corn oil groups. CONCLUSION: The oils effected changes in the blood lipid profile. A small amount of saturated fatty acids (tocopherol and tocotrienol) were favourable for the HDL-C increase. The presenct of tocorienols tended to decrease the TG and probably helped attenuate the unfavorable effects of the saturated fatty acids.
PMID: 15962906 [PubMed - indexed for MEDLINE]
Isolation of palm tocols using supercritical fluid chromatography.
Han NM, May CY, Ngan MA, Hock CC, Ali Hashim M.
Malaysian Palm Oil Board, Persiaran Institusi, Bandar Baru Bangi, 43000 Kajang, Selangor, Malaysia.
Crude palm oil contains 600 to 1000 ppm of tocols in the form of tocopherols and tocotrienols. These palm tocols have been isolated and analyzed in the past by various chromatographic techniques such as open column chromatography, high-performance liquid chromatography, as well as thin-layer chromatography. Supercritical fluid chromatography (SFC) has emerged as a more advanced chromatographic technique in recent years. The tocols present in palm oil are successfully isolated using SFC. Identification of these tocols is supported by various spectroscopic techniques such as 1H NMR, 13C NMR, and mass spectrometry.
PMID: 15768840 [PubMed - indexed for MEDLINE]
Tocotrienol-rich fraction from palm oil and gene expression in human breast cancer cells.
Nesaretnam K, Ambra R, Selvaduray KR, Radhakrishnan A, Canali R, Virgili F.
Malaysian Palm Oil Board, 6 Persiaran Institusi, Bandar Baru Bangi, 4300 Kajang, Selangor, Malaysia. sarnesar@mpob.gov.my
Vitamin E is important not only for its cellular antioxidant and lipid-lowering properties, but also as an antiproliferating agent. It has also been shown to contribute to immunoregulation, antibody production, and resistance to implanted tumors. It has recently been shown that tocotrienols are the components of vitamin E responsible for growth inhibition in human breast cancer cells in vitro as well as in vivo through estrogen-independent mechanisms. Although tocotrienols act on cell proliferation in a dose-dependent manner and can induce programmed cell death, no specific gene regulation has yet been identified. In order to investigate the molecular basis of the effect of a tocotrienol-rich fraction (TRF) from palm oil, we performed a cDNA array analysis of cancer-related gene expression in estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-231) human breast cancer cells. The human breast cancer cells were incubated with or without 8 mug/mL of tocotrienols for 72 h. RNA was subsequently extracted and subjected to reverse transcription before being hybridized onto cancer arrays. Tocotrienol supplementation modulated significantly 46 out of 1200 genes in MDA-MB-231 cells. In MCF-7 cells, tocotrienol administration was associated with a lower number of affected genes. Interestingly, only three were affected in a similar fashion in both cell lines: c-myc binding protein MM-1, 23-kDa highly basic protein, and interferon-inducible protein 9-27 (IFITM-1). These proteins are most likely involved in the cell cycle and can exert inhibitory effects on cell growth and differentiation of the tumor cell lines. These data suggest that tocotrienols are able to affect cell homeostasis, possibly independent of their antioxidant activity.
PMID: 15753141 [PubMed - indexed for MEDLINE]
Cardioprotection with palm tocotrienol: antioxidant activity of tocotrienol is linked with its ability to stabilize proteasomes.
Das S, Powell SR, Wang P, Divald A, Nesaretnam K, Tosaki A, Cordis GA, Maulik N, Das DK.
Cardiovascular Research Center, Univ. of Connecticut, School of Medicine, Farmington, CT 06030-1110, USA. ddas@neuron.uchc.edu
Tocotrienols, isomers of vitamin E, have been found to possess many health benefits. The present study was designed to determine whether tocotrienol has a direct cardioprotective role. Isolated rat hearts were perfused for 15 min with Krebs-Ringer bicarbonate buffer in the absence or presence of palm tocotrienol derived from the tocotrienol-rich fraction (0.035%) of palm oil (TRF). In another group of studies, the hearts were preperfused for 15 min in the presence of a c-Src inhibitor, 4-amino-5-(4-methylphenyl)-7-(t-butyl)-pyrazolo-3,4-d-pyrimidine (PPI). The hearts were then subjected to 30 min of global ischemia followed by 2 h of reperfusion. As expected, ischemia-reperfusion caused ventricular dysfunction, electrical rhythm disturbances, and increased myocardial infarct size. PPI or TRF could reverse the ischemia-reperfusion-mediated cardiac dysfunction. Ischemia-reperfusion also upregulated c-Src expression and phosphorylation. Although TRF only minimally affected c-Src expression, it significantly inhibited the phosphorylation of c-Src. Ischemia-reperfusion reduced 20S and 26S proteasome activities, an effect prevented by TRF pretreatment. PPI exerted a cardioprotective effect that is not mediated by the proteasome but, rather, through direct inhibition of c-Src. The results of this study support a role for c-Src in postischemic cardiac injury and dysfunction and demonstrate direct cardioprotective effects of TRF. The cardioprotective properties of TRF appear to be due to inhibition of c-Src activation and proteasome stabilization.
PMID: 15708953 [PubMed - indexed for MEDLINE]
Separation of vitamin E (tocopherol, tocotrienol, and tocomonoenol) in palm oil.
Ng MH, Choo YM, Ma AN, Chuah CH, Hashim MA.
Malaysian Palm Oil Board, Selangor, Malaysia.
Previous reports showed that vitamin E in palm oil consists of various isomers of tocopherols and tocotrienols [alpha-tocopherol (alpha-T), alpha-tocotrienol, gamma-tocopherol, gamma-tocotrienol, and delta-tocotrienol), and this is normally analyzed using silica column HPLC with fluorescence detection. In this study, an HPLC-fluorescence method using a C30 silica stationary phase was developed to separate and analyze the vitamin E isomers present in palm oil. In addition, an alpha-tocomonoenol (alpha-T1) isomer was quantified and characterized by MS and NMR. (alpha-T1 constitutes about 3-4% (40+/-5 ppm) of vitamin E in crude palm oil (CPO) and is found in the phytonutrient concentrate (350+/-10 ppm) from palm oil, whereas its concentration in palm fiber oil (PFO) is about 11% (430+/-6 ppm). The relative content of each individual vitamin E isomer before and after interesterification/transesterification of CPO to CPO methyl esters, followed by vacuum distillation of CPO methyl esters to yield the residue, remained the same except for alpha-T and gamma-T3. Whereas alpha-T constitutes about 36% of the total vitamin E in CPO, it is present at a level of 10% in the phytonutrient concentrate. On the other hand, the composition of gamma-T3 increases from 31% in CPO to 60% in the phytonutrient concentrate. Vitamin is present at 1160+/-43 ppm, and its concentrations in PFO and the phytonutrient concentrate are 4,040+/-41 and 13,780+/-65 ppm, respectively. The separation and quantification of alpha-T1 in palm oil will lead to more in-depth knowledge of the occurrence of vitamin E in palm oil.
PMID: 15691027 [PubMed - indexed for MEDLINE]
A developmental study on the appearance of tocopherols and tocotrienols in developing palm mesocarp (Elaeis guineensis).
Choo YM, Ma AN, Chuah CH, Khor HT, Bong SC.
Malaysian Palm Oil Board, 6, Persiaran Institusi, Bandar Baru Bangi, 43000 Kajang, Selangor, Malaysia. choo@mpob.gov.my
The concentration of vitamin E isomers, namely, alpha-tocopherol (alpha-T), alpha-tocotrienol, gamma-tocotrienol, and delta-tocotrienol in palm mesocarp at 4, 8, 12, 16, and 20 wk after anthesis (WAA) were quantified using HPLC coupled with fluorescence detection. alpha-T was detected throughout the palm fruits' maturation process, whereas unsaturated tocotrienols were found only in ripe palm fruits. These developmental results indicate that tocotrienols are synthesized between 16 and 20 WAA.
PMID: 15554155 [PubMed - indexed for MEDLINE]
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Alpha-tocotrienol provides the most potent neuroprotection among vitamin E analogs on cultured striatal neurons.
Osakada F, Hashino A, Kume T, Katsuki H, Kaneko S, Akaike A.
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Oxidative stress and apoptosis play pivotal roles in the pathogenesis of neurodegenerative diseases. We investigated the effects of vitamin E analogs on oxidative stress and apoptosis using primary neuronal cultures of rat striatum. A tocotrienol-rich fraction of edible oil derived from palm oil (Tocomin 50%), which contains alpha-tocopherol, and alpha-, gamma- and delta-tocotrienols, significantly inhibited hydrogen peroxide (H2O2)-induced neuronal death. Each of the tocotrienols, purified from Tocomin 50% by high-performance liquid chromatography, significantly attenuated H2O2-induced neurotoxicity, whereas alpha-tocopherol did not. alpha-, gamma- and delta-Tocotrienols also provided significant protection against the cytotoxicity of a superoxide donor, paraquat, and nitric oxide donors, S-nitrosocysteine and 3-morpholinosydnonimine. Moreover, tocotrienols blocked oxidative stress-mediated cell death with apoptotic DNA fragmentation caused by an inhibitor of glutathione synthesis, L-buthionine-[S,R]-sulfoximine. In addition, alpha-tocotrienol, but not gamma- or delta-tocotrienol, prevented oxidative stress-independent apoptotic cell death, DNA cleavage and nuclear morphological changes induced by a non-specific protein kinase inhibitor, staurosporine. These findings suggest that alpha-tocotrienol can exert anti-apoptotic neuroprotective action independently of its antioxidant property. Among the vitamin E analogs examined, alpha-tocotrienol exhibited the most potent neuroprotective actions in rat striatal cultures.
PMID: 15527824 [PubMed - indexed for MEDLINE]
Tocotrienol-rich fraction from palm oil affects gene expression in tumors resulting from MCF-7 cell inoculation in athymic mice.
Nesaretnam K, Ambra R, Selvaduray KR, Radhakrishnan A, Reimann K, Razak G, Virgili F.
Malaysian Palm Oil Board, Bandar Baru Bangi, 4300 Selangor, Malaysia. sarnesar@mpob.gov.my
It has recently been shown that tocotrienols are the components of vitamin E responsible for inhibiting the growth of human breast cancer cells in vitro, through an estrogen-independent mechanism. Although tocotrienols act on cell proliferation in a dose-dependent manner and can induce programmed cell death, no specific gene regulation has yet been identified. To investigate the molecular basis of the effect of tocotrienols, we injected MCF-7 breast cancer cells into athymic nude mice. Mice were fed orally with 1 mg/d of tocotrienol-rich fraction (TRF) for 20 wk. At end of the 20 wk, there was a significant delay in the onset, incidence, and size of the tumors in nude mice supplemented with TRF compared with the controls. At autopsy, the tumor tissue was excised and analyzed for gene expression by means of a cDNA array technique. Thirty out of 1176 genes were significantly affected. Ten genes were downregulated and 20 genes up-regulated with respect to untreated animals, and some genes in particular were involved in regulating the immune system and its function. The expression of the interferon-inducible transmembrane protein-1 gene was significantly up-regulated in tumors excised from TRF-treated animals compared with control mice. Within the group of genes related to the immune system, we also found that the CD59 glycoprotein precursor gene was up-regulated. Among the functional class of intracellular transducers/effectors/modulators, the c-myc gene was significantly down-regulated in tumors by TRF treatment. Our observations indicate that TRF supplementation significantly and specifically affects MCF-7 cell response after tumor formation in vivo and therefore the host immune function. The observed effect on gene expression is possibly exerted independently from the antioxidant activity typical of this family of molecules.
PMID: 15506241 [PubMed - indexed for MEDLINE]
Lack of oxidative stress in a selenium deficient area in Ivory Coast--potential nutritional antioxidant role of crude palm oil.
Tiahou G, Maire B, Dupuy A, Delage M, Vernet MH, Mathieu-Daude JC, Michel F, Sess ED, Cristol JP.
Dept. of Biochemistry, Hospital Lapeyronie, 191 Avenue du Doyen Gaston Giraud, 34295 Montpellier cedex 5, France.
BACKGROUND: Previous studies have described an important selenium deficiency in a mountain region (Glanle) in the west of Ivory Coast. AIM OF THE STUDY: To assess the antioxidant capacity of subjects from a selenium deficient area in Ivory Coast (Glanle region). METHODS: This study involved 57 subjects, 18 to 69 years old, living in the Glanle region and 56 healthy controls living in the southern coastal region (Bodou). In the Glanle region families consume basically a vegetarian and crude palm oil diet, whereas in the Bodou region, families eat a fish-based diet with principally refined palm oil. Fasting blood samples were collected to assess the following parameters: lipid status (plasma total lipids; total-, HDL and LDL-cholesterol; triglycerides; phospholipids; fatty acid composition), plasma protein status (total protein, albumin, transthyretin, orosomucoid, CRP, transferrin), antioxidant capacity (plasma selenium, uric acid, retinol, alpha-tocopherol and tocotrienols levels, plasma seleno-glutathione peroxidase (GSHPx) activity) and oxidative stress markers (malondialdehyde (MDA) and advanced oxidation protein products (AOPP)). RESULTS: The mountain region samples (Glanle) were characterized by significantly lower plasma albumin, total-, HDL- and LDL-cholesterol, retinol and selenium levels, plasma PUFA content and GSHPx activity, but significantly higher alpha-tocopherol index and total tocotrienol level, than controls from the coastal area (Bodou). These results suggest a higher exposure risk to oxidative stress for the mountain region subjects. However, the absence of oxidative damage in this group provides evidence of a selenium independent protection mechanism against oxidative stress. This protection is related to lower plasma LDL cholesterol and PUFA content, and to higher alpha-tocopherol index, delta and total tocotrienols. CONCLUSION: The long-term consumption of crude palm oil could be considered as an effective protective factor against oxidative stress.
PMID: 15490200 [PubMed - indexed for MEDLINE]
[Progression of tocotrienols]
[Article in Chinese]
Sun W, Yan Y, Dong F.
First Clinic College of Harbin Medical University, Harbin 150001, China.
Tocotrienols is an isoform of tocopherols. Tocotrienols consists of a chromanol nucleus and a lipophilic isoprenoid chain. Tocotrienols were found in high concentrations in palm oil and rice bran. Its discovery was mainly antioxidant and resistant to lipid peroxidation. Tocotrienols influenced cholesterol synthesis by directly regulated activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductae (HMG CoA reductase) and decreased cholesterol. Important novel antiproliferative and neuroprotective effects have found. Molecular structure and biological function of tocotrienols were reviewed in this paper.
Publication Types:
PMID: 15209019 [PubMed - indexed for MEDLINE]
Effects of tocopherols and tocotrienols on body composition and bone calcium content in adrenalectomized rats replaced with dexamethasone.
Ima-Nirwana S, Suhaniza S.
Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia. imasoel@medic.ukm.my
Long-term glucocorticoid treatment is associated with severe side effects, such as obesity and osteoporosis. A palm oil-derived vitamin E mixture had been shown previously to be protective against osteoporosis in rats given 120 microg/kg dexamethasone daily for 12 weeks. In this study we determined the effects of two isomers of vitamin E (i.e., palm oil-derived gamma-tocotrienol and the commercially available alpha-tocopherol, 60 mg/kg of body weight/day) on body composition and bone calcium content in adrenalectomized rats replaced with two doses of dexamethasone, 120 microg/kg and 240 microg/kg daily. Treatment period was 8 weeks. gamma-Tocotrienol (60 mg/kg of body weight/day) was found to reduce body fat mass and increase the fourth lumbar vertebra bone calcium content in these rats, while alpha-tocopherol (60 mg/kg of body weight/day) was ineffective. Therefore, in conclusion, palm oil-derived gamma-tocotrienol has the potential to be utilized as a prophylactic agent in prevention of the side effects of long-term glucocorticoid use.
PMID: 15117552 [PubMed - indexed for MEDLINE]
Tocotrienol-rich fraction of palm oil activates p53, modulates Bax/Bcl2 ratio and induces apoptosis independent of cell cycle association.
Agarwal MK, Agarwal ML, Athar M, Gupta S.
Department of Medical Elementology and Toxicology, Hamdard University, New Delhi, India.
Anti-cancer properties of palm oil have been attributed to the presence of tocotrienols and carotenoids. Studies from various laboratories have shown that tocotrienol-rich fraction (TRF) of palm oil inhibits cell growth and induces apoptosis in both preneoplastic and neoplastic cells. However, the mechanism by which TRF induces apoptosis remains largely unknown. Since several chemopreventive agents have been shown to utilize p53 pathway in negative regulation of cell growth, using human colon carcinoma RKO cells which express wild type p53, we investigated the effect of TRF on components of p53 signaling network. Treatment of cells with TRF resulted in a dose- and time- dependent inhibition of growth and colony formation. Further, TRF treatment of RKO cells resulted in the induction of WAF1/p21 which appears to be independent of cell cycle regulation and is transcriptionally upregulated in p53 dependent fashion. These results were further confirmed by using cells that express luciferase from a p53 responsive promoter where TRF treatment leads to activation of p53 reporter activity. TRF treatment also resulted in alteration in Bax/Bcl2 ratio in favor of apoptosis, which was associated with the release of cytochrome c and induction of apoptotic protease-activating factor-1. This altered expression of Bcl2 family members triggered the activation of initiator caspase-9 followed by activation of effector caspase-3. These signaling cascades lead to condensed chromatin, DNA fragmentation and shrinkage of cell membrane resulting into apoptosis. Our data suggest that TRF-induced apoptosis in colon carcinoma cells is mediated by p53 signaling network which appears to be independent of cell cycle association.
PMID: 14712090 [PubMed - indexed for MEDLINE]
Phytonutrient deficiency: the place of palm fruit.
Wattanapenpaiboon N, Wahlqvist MW.
Asia Pacific Health and Nutrition Centre, Monash Asia Institute, 8th Floor Menzies Building, Monash University,Wellington Road, Clayton, Melbourne, Victoria 3800, Australia. tikky.w@adm.monash.edu.au
The oil palm (Elaeis guineensis) is native to many West African countries, where local populations have used its oil for culinary and other purposes. Large-scale plantations, established principally in tropical regions (Asia, Africa and Latin America), are mostly aimed at the production of oil, which is extracted from the fleshy mesocarp of the palm fruit, and endosperm or kernel oil. Palm oil is different from other plant and animal oils in that it contains 50% saturated fatty acids, 40% unsaturated fatty acids, and 10% polyunsaturated fatty acids. The fruit also contains components that can endow the oil with nutritional and health beneficial properties. These phytonutrients include carotenoids (alpha-,beta-,and gamma-carotenes), vitamin E (tocopherols and tocotrienols), sterols (sitosterol, stigmasterol and campesterol), phospholipids, glycolipids and squalene. In addition, it is recently reported that certain water-soluble powerful antioxidants, phenolic acids and flavonoids, can be recovered from palm oil mill effluent. Owing to its high content of phytonutrients with antioxidant properties, the possibility exists that palm fruit offers some health advantages by reducing lipid oxidation, oxidative stress and free radical damage. Accordingly, use of palm fruit or its phytonutrient-rich fractions, particularly water-soluble antioxidants, may confer some protection against a number of disorders or diseases including cardiovascular disease, cancers, cataracts and macular degeneration, cognitive impairment and Alzheimer's disease. However, whilst prevention of disease through use of these phytonutrients as in either food ingredients or nutraceuticals may be a worthwhile objective, dose response data are required to evaluate their pharmacologic and toxicologic effects. In addition, one area of concern about use of antioxidant phytonutrients is how much suppression of oxidation may be compatible with good health, as toxic free radicals are required for defence mechanisms. These food-health concepts would probably spur the large-scale oil palm (and monoculture) plantations, which are already seen to be a major cause of deforestation and replacement of diverse ecosystems in many countries. However, the environmental advantages of palm phytonutrients are that they are prepared from the readily available raw material from palm oil milling processes. Palm fruit, one of only a few fatty fruits, is likely to have an increasingly substantiated place in human health, not only through the provision of acceptable dietary fats, but also its characteristic protective phytonutrients.
Publication Types:
PMID: 14506002 [PubMed - indexed for MEDLINE]
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