Chemopreventive effect of dietary d-alpha-tocopheryl succinate supplementation on precancer colon aberrant crypt formation and vitamin E analogue levels in young and old rats

This study examined the effects of dietary d-alpha-tocopheryl succinate (TS) in female rats, 20 mo (OLD) or 2 mo (YNG) of age, on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) and tissue distribution of d-alpha-tocopherol (alphaT), d-gamma-tocopherol (gammaT), and alphaTS. Rats were fed a commercial rodent chow supplemented with or without 1 (YNG) or 2 (OLD) g alphaTS/kg diet for 1 week prior to ip administration of AOM to induce colon ACF. The animals were sacrificed after 49 days of exposure. The results showed that OLD rats had significantly fewer ACF than YNG animals, and the percent body fat and serum triglycerides were significantly higher in the OLD group compared with the YNG. However, only OLD animals receiving alphaTS had significantly reduced numbers of larger ACF and significantly higher levels of colonic alphaT, gammaT, and alphaTS. These data support previous studies demonstrating that dietary alphaTS administration is protective against intestinal cancer. Also, this is the first study to show that alphaTS accumulates in most tissues following dietary exposure. We hypothesize that increased colon accumulation of fat-soluble vitamin E compounds and subsequent chemoprevention may be related to greater percent body fat and serum triglycerides in OLD animals receiving dietary TS.     

Organic solvent-soluble lipofuscin pigments and glutathione peroxidase in mouse brain and heart: effects of age and vitamin E

The effect of age and dietary supplementation of vitamin E or N,N'-diphenyl-p-phenylenediamine (DPPD) on organic solvent-soluble lipofuscin pigments (OLP) and glutathione peroxidase (GSH-Px) activity in mouse heart and brain was investigated. Four groups of 32 female weanling mice were fed a basal diet containing either 0, 30 or 300 ppm RRR-alpha-tocopheryl acetate (d-alpha-tocopheryl acetate) or 30 ppm DPPD from 2 to 18 mo of age. Neither GSH-Px activity nor dietary supplementation of vitamin E or DPPD had an effect on OLP concentrations in the brain or heart. OLP levels were two- to fourfold higher at 12 mo of age in the heart and were lower at 18 mo of age in the brain than at 2 or 9 mo of age. GSH-Px activity increased with age in the heart tissue of vitamin E-deficient and DPPD-supplemented mice only. No change in GSH-Px activity was observed in the brain due to diet or increasing age. These results suggested that OLP concentrations were not affected by dietary supplementation of vitamin E or DPPD but were affected by age-related factors in the mouse brain and heart.     

Lung eicosanoid synthesis is affected by age, dietary fat and vitamin E.

The effect of age, dietary fat type and all-rac-alpha-tocopheryl acetate (vitamin E) supplementation on ex vivo synthesis of lung eicosanoids was measured in C57BL/6NIA mice using a 2 (age) x 3 (fat) x 3 (vitamin E) factorial design. Young (3-mo-old) and old (24-mo-old) mice were fed a semipurified diet containing 5% (by wt) corn oil, coconut oil or fish oil supplemented with 30, 100 or 500 mg vitamin E/kg for 4 wk. Ex vivo synthesis of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (PGI2) were measured by RIA in lung homogenates. Old mice had significantly higher concentrations of TXB2 and PGI2 than did young mice, resulting in a significant increase in the TXB2:PGI2 ratio with aging. Young and old mice fed fish oil had significantly lower concentrations of PGI2 and TXB2 than those fed corn oil or coconut oil. The degree of reduction varied according to age and vitamin E status. Old mice fed fish oil and 30 mg vitamin E/kg diet had the lowest plasma vitamin E concentration and the highest TXB2:PGI2 ratio. The TXB2:PGI2 ratio was significantly reduced in old mice fed coconut oil or fish oil by vitamin E supplementation. Vitamin E supplementation (100 mg/kg) significantly increased PGI2 concentration in young mice fed coconut oil. Thus, significant changes in the capacity of lung to synthesize eicosanoids occur with age and are influenced by dietary fat type and vitamin E. J. Nutr.     

Influence of dietary fat, vitamin E, ethoxyquin and indomethacin on the synthesis of prostaglandin E2 in brain regions of mice

The regional brain synthesis of prostaglandin E2 (PGE2) of rats varies with age and dietary vitamin E. We investigated ex-vivo synthesis of PGE2 in brain regions of 24-mo-old male C57BL/6Nia mice. Mice were fed semipurified diets containing 1) 5% by weight of vitamin E-stripped corn oil, nonhydrogenated coconut oil or fish oil, or 2) 3.8% lard + 1.2% stripped corn oil (control), each supplemented with 30 or 500 mg of vitamin E per kg for 6 wk. In addition, two groups of mice were fed control diets containing 2500 mg of ethoxyquin/kg or 1 mg of indomethacin/(kg.day). Mice fed fish oil had lower (P less than 0.01) plasma alpha-tocopherol than those fed coconut oil. Vitamin E supplementation had no effect on the concentration of alpha-tocopherol in most brain regions. The rank order of PGE2 synthesis among all groups was cerebrum = cerebellum greater than midbrain greater than brainstem. Vitamin E supplementation tended to reduce brain PGE2 synthesis. Fat with 30 mg/kg of vitamin E in their diet. In the brainstem, fish oil significantly reduced PGE2 relative to mice fed corn oil. Ethoxyquin lowered plasma alpha-tocopherol by 42% and reduced the PGE2 synthesis in brain regions, and indomethacin reduced it by 50%. Thus, ethoxyquin and indomethacin significantly reduced the brain's regional capacity for PGE2 synthesis, whereas vitamin E was not effective for the period tested. The reduction of PGE2 synthesis in the brain with fish oil feeding in this study was not as notable as reported for other tissues unless combined with high-dose vitamin E supplementation.     

Pomegranate juice supplementation to atherosclerotic mice reduces macrophage lipid peroxidation, cellular cholesterol accumulation and development of atherosclerosis

Inhibition of lipid peroxidation contributes to the attenuation of macrophage cholesterol accumulation, foam-cell formation and atherosclerosis. Evidence suggests that nutritional antioxidants such as pomegranate juice (PJ) can contribute to the reduction of oxidative stress and atherogenesis. The goals of the present study were to determine whether such beneficial effects of PJ exist when supplemented to apolipoprotein E-deficient (E(0)) mice with advanced atherosclerosis and to analyze the antiatherosclerotic activity of a tannin-fraction isolated from PJ. Mice (4-mo-old) were supplemented with PJ in their drinking water for 2 mo and compared with age-matched placebo-treated mice, as well as to young (4-mo-old) control mice, for their mouse peritoneal macrophage (MPM) oxidative state, cholesterol flux and mice atherosclerotic lesion size. PJ supplementation reduced each of the proatherogenic variables determined in the present study compared with age-matched placebo-treated mice. It significantly induced serum paraoxonase activity and reduced MPM lipid peroxide content compared with placebo-treated mice and control mice. PJ administration to E(0) mice significantly reduced the oxidized (Ox)-LDL MPM uptake by 31% and MPM cholesterol esterification and increased macrophage cholesterol efflux by 39% compared with age-matched, placebo-treated mice. PJ consumption reduced macrophage Ox-LDL uptake and cholesterol esterification to levels lower than those in 4-mo-old, unsupplemented controls. PJ supplementation to E(0) mice with advanced atherosclerosis reduced the lesion size by 17% compared with placebo-treated mice. In a separate study, supplementation of young (2-mo-old) E(0) mice for 2 mo with a tannin fraction isolated from PJ reduced their atherosclerotic lesion size, paralleled by reduced plasma lipid peroxidation and decreased Ox-LDL MPM uptake. PJ supplementation to mice with advanced atherosclerosis reduced their macrophage oxidative stress, their macrophage cholesterol flux and even attenuated the development of atherosclerosis. Moreover, a tannin-fraction isolated from PJ had a significant antiatherosclerotic activity.     

Effects of maternal docosahexaenoic acid intake on visual function and neurodevelopment in breastfed term infants

BACKGROUND: Normal brain and visual development is thought to require exogenous docosahexaenoic acid (DHA; 22:6n-3) intake, but the amount needed is debatable. Because the supplementation of breastfeeding mothers with DHA increases the DHA content of their infants' plasma lipids, we hypothesized that it might also improve brain or visual function in the infants. OBJECTIVE: The objective was to determine the effect of DHA supplementation of breastfeeding mothers on neurodevelopmental status and visual function in the recipient infant. DESIGN: Breastfeeding women received capsules containing either a high-DHA algal oil ( approximately 200 mg DHA/d) or a vegetable oil (no DHA) for 4 mo after delivery. Outcome variables included the fatty acid pattern of maternal plasma phospholipid and milk lipids 4 mo postpartum, the fatty acid pattern of plasma phospholipids and visual function in infants at 4 and 8 mo of age, and neurodevelopmental indexes of the infants at 12 and 30 mo of age. RESULTS: Milk lipid and infant plasma phospholipid DHA contents of the supplemented and control groups were approximately 75% and approximately 35% higher, respectively, at 4 mo postpartum. However, neither the neurodevelopmental indexes of the infants at 12 mo of age nor the visual function at 4 or 8 mo of age differed significantly between groups. In contrast, the Bayley Psychomotor Development Index, but not the Mental Development Index, of the supplemented group was higher (P < 0.01) at 30 mo of age. CONCLUSION: DHA supplementation of breastfeeding mothers results in higher infant plasma phospholipid DHA contents during supplementation and a higher Bayley Psychomotor Development Index at 30 mo of age but results in no other advantages either at or before this age.     

Effect of selenite, vitamin E and N,N'-diphenyl-p-phenylenediamine on liver organic solvent-soluble lipofuscin pigments in mice

The present experiment was designed to investigate the effect of selenium (Se) supplementation, as sodium selenite, on organic solvent-soluble lipofuscin pigment (OLP) accumulation and glutathione peroxidase (GSH-Px) activity in the livers of mice fed varying levels of vitamin E or N,N'-diphenyl-p-phenylenediamine (DPPD). Four groups of 16 female, weanling mice each were fed either a vitamin E-deficient diet, a diet supplemented with 30 mg/kg or 300 mg/kg vitamin E (as RRR-alpha-tocopheryl acetate), or a diet supplemented with 30 mg/kg DPPD. Each diet contained 0.05 ppm Se. At 5 months of age, eight animals from each dietary group were supplemented with an additional 0.1 ppm Se, as sodium selenite, in their drinking water. The remaining animals were fed their original diets through the 9-month experimental period. Selenite supplementation resulted in a significant increase in OLP concentration and GSH-Px activity in the liver of mice fed vitamin E- or DPPD-supplemented diets. Normal levels of vitamin E and DPPD (30 mg/kg) were not sufficient to protect against the oxidative effects of selenite; however, 10 times the normal level of vitamin E (300 mg/kg) markedly suppressed this oxidative effect.     

Arginine enhances In vivo immune responses in young, adult and aged mice

Arginine supplementation enhances in vitro lymphocyte proliferation in healthy adult humans and in rodent models. Studies examining the effect of arginine supplementation on in vivo immune responses are lacking. The purpose of this study was to determine whether arginine supplementation could enhance in vivo immune responses in adult mice and reverse known age-associated alterations in immune function of young and aged mice. Mice (1, 10 and 33 mo old) were fed a 2% arginine or an isonitrogenous diet for 2 wk. Delayed-type hypersensitivity to 2,4-dinitrofluorobenzene-challenged ears and changes in popliteal lymph node weights to injected sheep red blood cells were measured. The mean percentage of increase in ear thickness in challenged vs. unchallenged ears was 27, 35 and 24% with arginine supplementation and 7, 12 and 0% with the isonitrogenous diet in the 1-, 10- and 33-mo-old mice, respectively (P 相似文献   

Influences of dietary restriction and age on liver enzyme activities and lipid peroxidation in mice

Dietary restriction extends maximum life span in rodents by unknown mechanisms. We compared livers from 12- and 24-mo-old mice fed control (C, approximately 95 kcal/wk) or restricted (R, approximately 55 kcal/wk) amounts of diet since 3 wk of age. We hypothesized that dietary restriction might alter the activity levels of enzymes with possible relevance to aging processes. The enzymes included several xenobiotic metabolizers, radical scavengers (catalase, superoxide dismutase, glutathione peroxidase), superoxide sources (xanthine oxidase, peroxisomal beta-oxidation of palmitoyl-CoA) and glucose-6-phosphatase. Lipid peroxidation (LP) was also measured. Comparing 12- and 24-mo-old mice, the strongest diet or age effect was an increased catalase activity for group R (42% higher at 12 mo, 64% at 24 mo). LP was clearly lower in group R at 12 mo (a 30% decrease) and somewhat lower (13%) at 24 mo than in group C. Similarly, in 12-mo-old C and R mice injected with either the P-450 inducer beta-naphthoflavone (beta-NF in corn oil) or with corn oil alone. R mice showed higher catalase activity (40-44%) and lower LP (43-46%) in both beta-NF-injected and vehicle-injected groups. These data suggest that if free radical damage is involved in aging, it may be a particular kind of damage, that is, that in part prevented by a selective increase in catalase activity.     

Coenzyme Q intake elevates the mitochondrial and tissue levels of Coenzyme Q and alpha-tocopherol in young mice

The main objective of this study was to resolve the issue of whether the amounts of Coenzyme Q (CoQ), which is endogenously synthesized in cells, can be elevated in tissues and mitochondria of young mice by dietary supplementation with CoQ10. The prevalent view is that the uptake of exogenous CoQ by tissues other than plasma and liver either does not occur or is quite minimal. Mice, 6 mo of age, were fed 0, 148 or 654 mg CoQ10/(kg body x d) in their diets for 11 wk. CoQ10 intake enhanced both CoQ9 and CoQ10 homologues in the plasma, and in homogenates and mitochondria of liver, heart and skeletal muscle. CoQ was elevated in brain mitochondria, but not in the brain homogenate. The uptake of exogenous CoQ was higher in mitochondria of heart and skeletal muscle than those in liver. CoQ10 administration also elevated the alpha-tocopherol concentration in tissue homogenates and their mitochondria, thereby providing an in vivo indication of the "sparing" effect of CoQ on alpha-tocopherol. Results of this study demonstrate that, contrary to the historical view, both total and mitochondrial CoQ concentrations in the heart and skeletal muscle and in the mitochondria of brain of young mice can be augmented by dietary supplementation. Furthermore, CoQ intake enhances the antioxidative potential of tissues by elevating the endogenous amounts of alpha-tocopherol.     

Dietary coenzyme Q10 and vitamin E alter the status of these compounds in rat tissues and mitochondria

Vitamin E (VE) and coenzyme Q (CQ) are essential for maintaining functions and integrity of mitochondria, and high concentrations of these compounds are found in their inner membranes. This study was conducted to examine the interaction between exogenously administered CQ10 and VE in rats. Male Sprague-Dawley rats (12 mo old) were fed a basal diet (10 IU VE or 6.7 mg RRR-alpha-tocopherol equivalent) supplemented with either 0 or 500 mg CQ10, and 0, 100 or 1310 IU VE/kg diet for 14 or 28 d. Liver, spleen, heart, kidney, skeletal muscle, brain and serum were analyzed for the levels of CQ10, CQ9 and VE. CQ10 supplementation significantly (P: < 0.05) increased CQ10 concentration in the liver and spleen (total and mitochondria) and serum, but not in other organs. Interestingly, rats supplemented with CQ10 plus 100 IU VE/kg diet had significantly higher CQ10 levels in the liver and spleen, whereas those supplemented with CQ10 plus 1310 IU VE/kg diet had lower levels, compared with those supplemented with CQ10 alone. As expected, dietary VE increased VE content in all of the organs analyzed in a dose-dependent manner. However, rats fed the basal diet supplemented with CQ10 had significantly higher VE levels in liver (total and mitochondria) than those not receiving CQ10 supplementation. CQ9 levels were higher in the liver and spleen, lower in skeletal muscle and unaltered in brain, serum, heart and kidney of rats supplemented with CQ10 compared with the controls. These data provide direct evidence for an interactive effect between exogenously administered VE and CQ10 in terms of tissue uptake and retention, and for a sparing effect of CQ10 on VE. Data also suggest that dietary VE plays a key role in determining tissue retention of exogenous CQ10.     

Age and dietary form of vitamin K affect menaquinone-4 concentrations in male Fischer 344 rats

Phylloquinone, the primary dietary form of vitamin K, is converted to menaquinone-4 (MK-4) in certain tissues. MK-4 may have tissue-specific roles independent of those traditionally identified with vitamin K. Fischer 344 male rats of different ages (2, 12, and 24 mo, n = 20 per age group) were used to compare the conversion of phylloquinone to MK-4 with an equivalent dose of another dietary form of vitamin K, 2',3'-dihydrophylloquinone. Rats were age- and diet-group pair-fed phylloquinone (198 +/- 9.0 microg/kg diet) or dihydrophylloquinone (172 +/- 13.0 microg/kg diet) for 28 d. MK-4 was the primary form of vitamin K in serum, spleen, kidney, testes, bone marrow, and brain myelin fractions, regardless of age group. MK-4 concentrations were significantly lower in kidney, heart, testes, cortex (myelin), and striatum (myelin) in the dihydrophylloquinone diet group compared with the phylloquinone diet group (P < 0.05). The MK-4 concentrations in 2-mo-old rats were lower in liver, spleen, kidney, heart, and cortex (myelin) but higher in testes compared with 24-mo-old rats (P < 0.05). However, there were no age-specific differences in MK-4 concentrations among the rats fed the 2 diets. These data suggest that dihydrophylloquinone, which differs from phylloquinone in its side phytyl chain, is absorbed but its intake results in less MK-4 in certain tissues. Dihydrophylloquinone may be used in models for the study of tissue-specific vitamin K deficiency.     

Reduced brain norepinephrine metabolism in obese (ob/ob) mice is not normalized by tyrosine supplementation

Five-week-old female lean and obese (ob/ob) mice were fed a 20% protein diet (1.1% tyrosine) or a 20% protein diet supplemented with tyrosine (4% tyrosine). On d 4 of supplementation, brain norepinephrine (NE) synthesis rate and brain efflux of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), a major metabolite of NE in mouse brain, were measured after administration of the monoamine oxidase inhibitor pargyline. Control obese mice had a lower rate of NE synthesis and a lower MHPG efflux than lean controls. Tyrosine supplementation elevated brain tyrosine concentration twofold, but had no effect on NE synthesis rate or MHPG efflux in either group. Likewise, tyrosine supplementation for up to 1 mo had no effect on food intake, oxygen consumption or body weight in obese mice and only a transient effect in lean mice, in which oxygen consumption was higher on d 2 and 3 and food intake was higher on d 3 and 4 compared with nonsupplemented lean mice. We conclude that tyrosine availability is not a limiting factor in the reduced brain noradrenergic activity of obese mice.     

Anti-obesity effects of artificial planting blueberry (Vaccinium ashei) anthocyanin in high-fat diet-treated mice

This study aimed to evaluate the anti-obesity effects of artificial planting blueberry (Vaccinium ashei) anthocyanin (BA) in high-fat diet-induced obese male C57BL/6 mice. BA at doses of 50, 100, and 200?mg/kg was supplemented in the daily food of obese C57BL/6 mice during an 8-week experiment. Our findings indicate that consumption of BA at high doses reduced body weight by 19.4%, whereas both low and middle doses did not affect the body weight. Furthermore, BA supplementation at high dose could effectively decrease serum glucose, attenuate epididymal adipocytes, improve lipid profiles, and significantly down-regulate expression levels of TNFα, IL-6 PPARγ, and FAS genes. Therefour, BA might alter bodyweight by suppressing fatty acid synthesis and alleviating inflammation.     

Mitotic activity in mice is suppressed by energy restriction-induced torpor.

We monitored core body temperature by telemetry in energy-restricted (201 kJ/wk) and control (397 kJ/wk) C57BL/6 and SHN/C3H F1 mice to determine whether torpor may be involved in the suppression of mitotic activities resulting from energy restriction. The energy restriction regimen employed inhibited the development of cancer and greatly extended longevity in both these mouse strains. Male and female C57BL/6 mice subjected to energy restriction from 4 wk of age and tested at 3 mo of age became torporific (body temperature less than 31 degrees C) at ambient air temperatures of 20-22 degrees C, whereas control animals stayed euthermic (greater than 35 degrees C). Energy restriction also induced torpor in 3- and 13-mo-old SHN/C3H F1 female mice, whereas 3-, 13- and 24-mo-old control mice were euthermic. Energy restriction decreased mitotic activities to approximately 30% of control values in both jejunum and epidermis in 3-mo-old female C57BL/6 mice maintained at 20-22 degrees C. However, this suppression of mitotic activities was antagonized by housing the energy-restricted mice at 30 degrees C for 2 wk, indicating that torpor plays a substantial role in suppressing mitotic activities in energy-restricted mice.     

Age and copper intake do not affect copper absorption,measured with the use of 65Cu as a tracer,in young infants

BACKGROUND: Copper homeostasis involves a high degree of regulation in which changes in absorption and biliary excretion are the main mechanisms. Whether neonates and small infants can make these changes efficiently is unknown. OBJECTIVE: We evaluated the effect of age and copper intake on copper absorption in infants during the first 3 mo of life. DESIGN: Thirty-nine healthy infants (19 infants aged 1 mo and 20 infants aged 3 mo) were selected. One-half of the subjects were randomly assigned to receive oral supplementation of 80 mg Cu (as copper sulfate). kg body wt(-1). d(-1) for 15 d. At the end of the trial, copper absorption was measured by using orally administered (65)Cu as a tracer and fecal monitoring of recovered (65)Cu. RESULTS: Mean (+/- SD) copper absorption at 1 mo of age was 83.6 +/- 5.8% and 74.8 +/- 9.1% for the unsupplemented and supplemented infants, respectively. The corresponding figures at 3 mo of age were 77.6 +/- 15.2% and 77.7 +/- 11.3%. A two-way analysis of variance showed that age, copper supplementation, and the interaction between age and copper supplementation did not have a significant effect on copper absorption. There was an inverse correlation between total fecal copper and the percentage of (65)Cu absorption (r = -0.50, P < 0.003). CONCLUSION: Copper absorption in young infants is high but does not respond to copper intake within the range tested.     

Vegetables affect the expression of genes involved in anticarcinogenic processes in the colonic mucosa of C57BL/6 female mice

There is abundant epidemiological evidence that vegetable consumption decreases colorectal cancer (CRC) risk. However, the molecular targets in the genome are mostly unknown. The present study investigated the effects of vegetable consumption on gene expression in the colon mucosa of female C57Bl/6 mice using cDNA microarray technology. Mice were fed one of 8 diets: a control diet containing no vegetables (diet 1); a diet containing 100 g/kg (diet 2, 10% dose), 200 g/kg (diet 3, 20% dose), or 400 g/kg (diet 4, 40% dose) of a vegetable mixture; or a diet containing 70 g/kg of cauliflower (diet 5, 7% dose), 73 g/kg of carrots (diet 6, 7.3% dose), 226 g/kg of peas (diet 7, 22.6% dose); or 31 g/kg of onions (diet 8, 3.1% dose). The vegetable mixture used in diets 2 to 4 consisted of the 4 individual vegetables used in diets 5 to 8: cauliflower (30% wet wt), carrots (30% wet wt), peas (30% wet wt), and onions (10% wet wt). To assess gene expression changes, colonic mucosal cells were collected after the mice were killed. Total RNA was isolated and microarray technology was used to measure the expression levels of 602 genes simultaneously. For 39 genes, significant dose-dependent effects were found, although in general the relations were not linear. For 15 genes, the altered expression could indeed explain reduced cancer risk at various stages of CRC development. Eleven genes were modulated by the vegetable mixture as well as by one or more of the individual vegetables. For 7 of the genes, the modulation by the mixture was due to the effect of a particular vegetable. These genes are of particular interest because they were consistently affected and could be involved in the prevention of CRC by vegetable consumption.     

A nucleoside-nucleotide mixture may reduce memory deterioration in old senescence-accelerated mice

We investigated the effects of a mixture of dietary nucleosides and nucleotides (NS + NT) on memory in 1- and 7-mo-old senescence-accelerated mice (SAM). Memory retention was studied with passive avoidance (step-through) and active avoidance (shuttle) tests. For 14 wk, mice in the control groups were fed a 20 g of casein/100 g diet, whereas the NS + NT groups were fed this diet supplemented with a 0.5 g of NS + NT mixture/100 g. All mice were killed at wk 14, and we studied the brain histopathology. Lipofuscin, monovacuoles and multiple vacuoles of various brain regions were measured. Body weight, food intake and ambulatory activity did not differ between the control and NS + NT groups. In old mice, the time of passive avoidance was significantly higher in the NS + NT group than in the control group at d 1 and 7 (P: < 0.05). However, such an effect of NS + NT was not observed in young mice. In the active avoidance test, the incidence of successful avoidance in old mice was higher in the NS + NT group than in the control group at d 1 and 2 (P: < 0.05). The percentages of specific brain cells containing lipofuscin were lower in NS + NT groups than in the control groups in both young and old mice (P: < 0.05). The number of monovacuoles and multiple vacuoles in specific brain regions tended to be lower (P: = 0.1-0.25) in NS + NT than in control groups, with significant differences in the microvacuoles of the middle cortex of young mice and in the multiple vacuoles in the hind cortex of old mice (P: < 0. 05). These results suggest that increased dietary NS + NT may be associated with decreases in the age-induced deterioration of brain morphology and certain memory tasks.     

Supplementation with tocotrienol-rich fraction alters the plasma levels of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor from young and old individuals

Purpose

Tocotrienol possess beneficial effects not exhibited by tocopherol. In vitro studies using animal models have suggested that these effects are caused via modulation of gene and protein expression. However, human supplementation studies using tocotrienol-rich isomers are limited. This study aims to identify plasma proteins that changed in expression following tocotrienol-rich fraction (TRF) supplementation within two different age groups.

Methods

Subjects were divided into two age groups—32 ± 2 (young) and 52 ± 2 (old) years old. Four subjects from each group were assigned with TRF (78 % tocotrienol and 22 % tocopherol, 150 mg/day) or placebo capsules for 6 months. Fasting plasma were obtained at 0, 3, and 6 months. Plasma tocopherol and tocotrienol levels were determined. Plasma proteome was resolved by 2DE, and differentially expressed proteins identified by MS. The expressions of three proteins were validated by Western blotting.

Results

Six months of TRF supplementation significantly increased plasma levels of tocopherols and tocotrienols. Proteins identified as being differentially expressed were related to cholesterol homeostasis, acute-phase response, protease inhibitor, and immune response. The expressions of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor were validated. The old groups showed more proteins changing in expression.

Conclusions

TRF appears to not only affect plasma levels of tocopherols and tocotrienols, but also the levels of plasma proteins. The identity of these proteins may provide insights into how TRF exerts its beneficial effects. They may also be potentially developed into biomarkers for the study of the effects and effectiveness of TRF supplementation.