Effect Of Α-tocopherol Research Articles

Dependence of protective effect of α-tocopherol on its concentration and time of action on pc12 cells under conditions of oxidative stress

At the short-term incubation (0.5 and 1.5 h) of cells of the PC12 neuronal line with alpha-tocopherol, its protective effect against the cytotoxic hydrogen peroxide action was increased with rise of its concentration in samples; the protection was practically absent at action of nanomolar antioxidant concentrations, but was well expressed at its micromolar concentrations. These data agree with the concept that alpha-tocopherol increases the cell living activity by reacting directly with free radicals, which leads to formation of the less reactive compounds deprived of non-paired electron. The evidence is obtained that at the long-term action on PC12 cells, alpha-tocopherol not only in micro-, but also in nanomolar concentrations increases statistically significantly the cell living activity under conditions of oxidative stress. As follows from the obtained data, an important role in realization of the alpha-tocopherol protective effect at the long-term incubation with it seems to be played by modulation by this antioxidant of activity of protein kinase activated by extracellular signaling, phosphatidylinosite 3-kinase, and protein kinase C.

Alpha-tocopherol at nanomolar concentrations increases the viability of PC12 cells under oxidative stress conditions. The effects of modulation of signaling systems

We found that long-term preincubation of neuronal-like PC12 cells with α-tocopherol at micro- as well as nanomolar concentrations significantly increased cell viability under oxidative stress conditions. We discovered that the protective effect of α-tocopherol increases with an increase in its concentration in the 1–100 nM range, while its effects at concentrations of 100 nM, 1, 10, and 100 μM were similar when α-tocopherol was applied to cells 12–18 h prior to H2O2. An important role in the protective effect of long-term pre-incubation of cells with α-tocopherol at various concentrations is probably related to its modulatory influence on the activities of protein kinase C, extracellular signal-activated protein kinase, and phosphatidylinositol 3-kinase. Short-term preincubation of PC12 cells with this antioxidant at nanomolar concentrations for 0.5 or 1.5 h practically did not influence cell viability, while the protective effect of α-tocopherol at micromolar concentrations was probably related to its ability to terminate free-radical reactions due to direct interactions with free radicals.

Modulatory Action of α-Tocopherol on Erythrocyte Membrane Adenosine Triphosphatase against Radiation Damage in Oral Cancer

To investigate the possible effects of α-tocopherol on erythrocyte membrane adenosine triphosphatases against radiation damage in oral cancer patients. Adenosine triphosphatase activities were analysed in oral cancer patients before and after radiotherapy (at a dosage of 6000 cGY in five fractions per week for a period of six weeks) and after supplemented with α-tocopherol (400 IU per day for entire period of radiotherapy). The membrane bound enzymes such as Na(+)/K(+)-ATPase, Ca(2+)-ATPase, Mg(2+)-ATPase and some trace elements were altered in oral cancer patients before and after radiotherapy. Supplemented with α-tocopherol modulates the erythrocyte membrane which is damaged by radiotherapy which suggests that α-tocopherol protects the erythrocyte membrane from radiation damage in oral cancer patients.

Abstract B92: Serum total and HDL cholesterol and risk of prostate cancer

Abstract Background: There has been growing support for the hypothesis that low cholesterol may protect against prostate cancer with a poorer prognosis. Studies suggest a decreased risk of high-grade prostate cancer in men with lower circulating total cholesterol, and that statin drugs may protect against aggressive prostate cancer. Confirmation of these findings in additional populations and examination of lipoprotein subfractions is needed. We prospectively examined prostate cancer risk and serum total and HDL cholesterol in the ATBC Study cohort. Methods: The ATBC Study was a randomized controlled trial conducted among male smokers in Finland to determine the effects of α-tocopherol and β-carotene supplements on cancer incidence. Fasting blood samples were collected at baseline (1985 — 1988), and total and HDL cholesterol were measured for all participants (n=29,133). Cohort follow-up continues through the Finnish Cancer Registry and the Register of Causes of Death. Cox proportional hazards models were used to estimate the relative risk of overall (n=2,041), high stage (≥ TNM stage III or AJC stage 3; n=412), high grade (Gleason sum ≥ 7; n=231), aggressive (either high stage or high grade; n=461), and non-aggressive (neither high stage nor high grade; n=829) prostate cancer by categories of total (<200, 200 — <240, ≥240 mg/dL) and HDL (<40, 40 — <60, ≥60 mg/dL) cholesterol. Multivariable models adjusted for age, serum α-tocopherol, family history of prostate cancer, education, and urban residence. Further adjustment for the following factors did not alter the results: α-tocopherol and β-carotene supplementation group, serum β-carotene, cigarettes per day, years smoked, physical activity, marital status, and intake of total energy, total fat, fruits and vegetables, red meat, alcohol, vitamin A, vitamin D, and calcium. Results: Men with high serum total cholesterol were at increased risk of prostate cancer, particularly high stage disease (≥240 vs. <200 mg/dl: HR=1.26, 95% CI 0.92 — 1.71, p-trend = 0.03). Stratification by follow-up time showed that the increased risk of prostate cancer for men with higher total cholesterol was limited to cases diagnosed at least 10 years after baseline. After excluding the first 9 years of follow-up, men with higher serum total cholesterol were at an increased risk of overall (≥240 vs. <200: HR=1.22, 95% CI 1.03 — 1.44, p-trend=0.01) and advanced-stage (≥240 vs. <200: HR=1.85, 95% CI 1.13 — 3.03, p-trend=0.05) prostate cancer. Higher HDL cholesterol appeared related to decreased risk of prostate cancer, overall and all clinical subtypes, throughout the follow-up period. Conclusion: In this population of male smokers with a low prevalence of PSA screening, high serum total cholesterol was associated with an increased risk of advanced prostate cancer, but only among cases diagnosed at least 10 years after baseline. Further, there was a suggestion that high HDL cholesterol reduced the risk of all clinical subtypes of prostate cancer. These results support previous studies and, indirectly, support the hypothesis that statin drugs may reduce the risk of prostate cancer with a poorer prognosis by lowering cholesterol concentrations. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B92.

Role of α-tocopherol in cellular signaling: α-tocopherol inhibits stress-induced mitogen-activated protein kinase activation

Tocopherols belong to the plant-derived poly phenolic compounds known for antioxidant functions in plants and animals. Activation of mitogen-activated protein kinases (MAPK) is a common reaction of plant cells in defense-related signal transduction pathways. We report a novel non-antioxidant function of α-tocopherol in higher plants linking the physiological role of tocopherol with stress signalling pathways. Pre-incubation of a low concentration of 50 μM α-tocopherol negatively interferes with MAPK activation in elicitor-treated tobacco BY2 suspension culture cells and wounded tobacco leaves, whereas pre-incubated BY2 cells with α-tocopherol phosphate did not show the inhibitory effect on stimuli-induced MAPK activation. The decreased MAPK activity was neither due to a direct inhibitory effect of α-tocopherol nor due to the induction of an inhibitory or inactivating activity directly affecting MAPK activity. The data support that the target of α-tocopherol negatively regulates an upstream component of the signaling pathways that leads to stress dependent MAPK activation.

Development of oxygen scavenging system containing a natural free radical scavenger and a transition metal

A natural free radical scavenger, α-tocopherol, and a transition metal in an oxygen scavenging system were evaluated as a possible oxygen scavenger. The effects of α-tocopherol, transition metal, moisture, and thermal processing on oxygen scavenging capability were investigated. An initial, cup headspace oxygen content (%) of 20.9% was decreased to 18.0% after thermal processing and 60 days of storage at room temperature when the oxygen scavenging system containing α-tocopherol (500 mg) and transition metal (100 mg) was utilised. α-Tocopherol and a transition metal were required for optimum oxygen scavenging capability, otherwise the oxygen scavenging capability decreased. The oxygen content (%) decreased further to 17.1% when the amount of transition metal increased from 100 to 150 mg. In this research, α-tocopherol (500 mg) and transition metal (150 mg) had an oxygen scavenging capacity of 6.72 ml O 2/g and an oxygen scavenging rate of 0.11 ml O 2/g•day. Results indicated that α-tocopherol and transition metal in oxygen scavenging system coupled with thermal processing can be used as an effective oxygen scavenger.

Effects of α-tocopherol, β-carotene and ascorbyl palmitate on oxidative stability of butter oil triacylglycerols

Butter oil triacylglycerols (BO-TAGs), free of antioxidants, including β-carotene, were obtained via sequential treatments with activated carbon (AC) adsorption and alumina column chromatography. α-Tocopherol, β-carotene and ascorbyl palmitate (AP) were added to BO-TAGs, individually, or in different combinations. An accelerated oven-oxidation test was carried out at 60 °C to determine the most effective dosages of the antioxidants. Among the antioxidants evaluated, α-tocopherol was found to be the most effective, at the concentration of 50 μg/g. To determine the possible synergism between the antioxidants, binary or ternary combinations of α-tocopherol, β-carotene and AP were added to BO-TAGs at concentrations of 50, 5, and 50 μg/g, respectively. Ternary combinations of these antioxidants were significantly better in retarding oxidation than were binary blends of α-tocopherol with β-carotene or AP. However, a prooxidant effect was observed, especially when β-carotene and AP were used individually or in binary combination.

Abstract 2799: Serum vitamin D and risk of bladder cancer in the ATBC Study

Abstract Background: Urinary bladder cancer is an important health concern in developed countries, particularly for men, among whom incidence is 3-5 times greater than in women. Vitamin D is thought to protect against cancer at many sites. However, to our knowledge, no studies have examined the association between serum vitamin D and bladder cancer. Methods: Within the ATBC Study, a randomized controlled trial conducted to determine the effects of α-tocopherol and β-carotene supplements on cancer incidence, 250 bladder cancer cases were randomly sampled by month of blood collection such that there were 25 cases included from each month with 25 cases total from June - August because fewer blood collections were conducted during the summer months. Controls were sampled from ATBC study participants who were alive and cancer free at the time the case was diagnosed and were matched 1:1 with cases on age at randomization (± 1 year) and date of blood collection (± 30 days). Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals of bladder cancer by a priori categories of baseline serum 25-hydroxy vitamin D (<25, 25 - <37.5, 37.5 - <50, ≥ 50 nmol/L). Results: After multivariable adjustment, lower serum vitamin D was associated with a statistically significantly increased risk of bladder cancer (OR, 95% CI vs. ≥ 50 nmol/L; 37.5 - <50 nmol/L: 2.04, 1.13 − 3.70; 25 - <37.5 nmol/L: 1.90, 1.07 − 3.35; <25 nmol/L: 1.83, 1.06 − 3.14; p-trend = 0.03), although the risk did not appear to increase with progressively lower vitamin D levels. Rather, men in any category of serum vitamin D below 50 nmol/L were at approximately two-fold risk compared to men with serum vitamin D ≥50 nmol/L (OR, 95% CI: 1.91, 1.20 − 3.04; p value = 0.006). Although the results were not statistically significant, there was a suggestion that the vitamin D - bladder cancer association was stronger among men who smoked less, were not assigned to the α-tocopherol intervention arm, or whose blood samples were obtained during the sunnier months. Conclusion: In this population of male smokers, lower vitamin D was associated with an increased risk of bladder cancer. Future studies should examine this association in other populations, especially women and non-smokers. Replication in a larger sample may clarify possible subtle effect modification by smoking, season, and intake of other nutrients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2799.

Dihydroperoxidation facilitates the conversion of lipids to aldehydic products via alkoxyl radicals

The mechanisms of formation of many aldehydic lipid oxidation products remain unclear, and the involvement of peroxyl radical additions in some cases was recently suggested. Here, the effect of α-tocopherol, a peroxyl radical trap, on the formation of aldehydic phospholipids from a phosphatidylcholine hydroperoxide was studied by electrospray ionization mass spectroscopy (ESI-MS). Based on the observed differential enhancement or suppression of formation of different aldehydes, new pathways are deduced for aldehyde formation via alkoxyl radicals derived from dihydroperoxy derivatives.

Synergic effects of α-tocopherol and β-carotene on tert-butylhydroperoxide-induced HepG2 cell injury

Oxidative stress produced by the dietary or chemical substrates is one of the major causes of liver cell injury. In this study, we compared the effects of two dietary antioxidants, alpha-tocopherol (alpha-T) and beta-carotene (beta-C) against tert-butyl hydroperxide (tBHP)-induced oxidative stress in human hepatoma HepG2 cells. Cell proliferation, lipid peroxidation (LPO), cellular lactate dehydrogenase (LDH), [3H]-aflatoxin B1(AFB1)-DNA adduct formation, and cytochrome P450 2E1 (CYP2E1) expression were determined after antioxidants were added to the tBHP-stressed cells. When compared to an ethanol-based control, all biomarkers for the cell damage were significantly increased by treatments. Treatments of beta-C or the combination of two antioxidants at 50 ppm for 48 h enhanced cell proliferation (P < 0.05) compared to tBHP control. The antioxidative and cytoprotective actions of alpha-T and beta-C, alone or in combination, were associated with modulation of microsomal CYP2E1 expression, corresponding to the regulation of LPO production (P < 0.0001). Our results indicate that alpha-T and beta-C may contribute differently to protection of cellular membrane disruption in CYP2E1-expressing HepG2 cells. Moreover, the combination of alpha-T and beta-C appears to impel the greater protection of pathogenic processes of oxidative stress in liver.

Effects of α-tocopherol and ternatin antioxidants on morphology and activation of goat preantral follicles in vitro cultured

The effects of α-tocopherol and ternatin on the morphology, activation, and growth of goat preantral follicles in vitro cultured, for one or five days, were evaluated. Ovarian fragments were immediately fixed (non-cultured control) or in vitro cultured for one or five days in Minimum Essential Medium (MEM) with or without α-tocopherol or ternatin supplementation, both at concentrations of 5, 10, or 15µM, corresponding to the following treatments: MEM, TOC5, TOC10, TOC 15, TER5, TER10, and TER15. The percentages of morphologically normal preantral follicles in non-cultured ovarian tissue (control) was 73.2% and after five days of culture, there was a decrease on these percentages in all treatments (P&lt;0.05) when compared with non-cultured control. Culture of ovarian cortex for five days increased the percentages of follicular activation in all treatments (P&lt;0.05). Ultrastructural analysis did not confirm the integrity of caprine preantral follicles cultured for five days in medium containing antioxidants. This study demonstrated that α-tocopherol and ternatin can promote follicular activation; however, addition of these antioxidants in the tested concentrations reduced the follicular viability after in vitro culture.

Effect of α-tocopherol on the synthesis of phosphatidylglycerol catalyzed by phospholipase D in an aqueous system

Phosphatidylglycerol (PG) was synthesized from several phosphatidylcholines (PCs) via phospholipase D (PLD)-catalyzed transphosphatidylation in an aqueous system. The yield of PG were 71 and 68 mol% from soybean PC and egg yolk PC, respectively, under the optimum reaction conditions of 50 micromol PC, 10 mmol glycerol, 3 ml of acetate buffer, 1.6 U PLD, and 30 micromol CaCl(2) at 37 degrees C for 48 h. In case of salmon roe PC with 14.3% eicosapentaenoic acid and 26.8% docosahexaenoic acid, the PG yield increased to 94 mol% by addition of 46 mumol alpha-tocopherol, although the PG yield was only 10% in absence of alpha-tocopherol.

Effect of α-tocopherol on carbon tetrachloride intoxication in the rat liver

Effect of α-tocopherol on carbon tetrachloride intoxication in the rat liver

In vitro Effect of α-tocopherol and Ascorbic Acid Supplementation on Immunological Indicators in Bovine Leukocytes following Transportation

The aim of the present study was to evaluate the effect of two different antioxidants, α-tocopherol and ascorbic acid, on the chemotactic activity and susceptibility to Mannheimia haemolytica leukotoxin (Lkt) of white blood cells obtained from calves exposed to transport in vitro. Both antioxidants used were found to affect the chemotactic activity of white blood cells. Supplementation of α-tocopherol at a concentration of 0.2 mg/ml and 0.5 mg/ml induced significant (P ⪬ 0.05) increase of chemotactic activity in white blood cells compared to control. In case of ascorbic acid supplementation the highest chemotactic activity was observed at a concentration of 0.5 mg/ml. The results obtained in microtitration (MTT) assay also suggest that high concentrations of α-tocopherol (0.5 mg/ml) play a role in protecting bovine leukocytes against the cytotoxic effect of Lkt, the susceptibility of the leukocytes on M. haemolytica Lkt was lower in comparison to control about 6%. The antioxidants used in this study have been found to have a protective effect on cells participating in the immune response to M. haemolytica. This particularly applies to high concentrations of α-tocopherol. The clinical aspect of these results may lie in protection of leukocytes exposed to leukotoxin of M. haemolytica. It should be emphasized that the results provide only partial information on the effect of the antioxidants studied on cells participating in an organism’s defence mechanisms. For an evaluation that would enable proper prevention of bovine respiratory diseases, research should be continued and expanded to include analysis of cellular structures.

Effect of α-tocopherol on carbon tetrachloride intoxication in the rat liver

Carbon tetrachloride (1 ml/kg body weight as a 1:1 mixture of CCl(4) and mineral oil) was orally administered to rats. After 12 h, the activity of plasma ALT (alanine aminotransferase) was significantly higher than that of the control group, and plasma ALT and AST (aspartate aminotransferase) activities significantly increased 24 h after CCl(4) administration. These results indicated that the necrotic process had initiated at about 12 h and developed thereafter. After 6-24 h of CCl(4) administration, the hepatic level of vitamin C, the most sensitive indicator of oxidative stress, decreased significantly, indicating that oxidative stress was significantly enhanced 6 h after CCl(4) intoxication and thereafter. Oral administration of vitamin E (1 ml/kg body weight as a 1:1 mixture of alpha-tocopherol and mineral oil) 12 h before CCl(4) administration caused a significant elevation of liver vitamin E level and ameliorated liver necrosis 24 h after CCl(4) intoxication based on plasma AST and ALT. Vitamin E also significantly restored the hepatic vitamin C concentration 12 and 24 h after CCl(4) intoxication, demonstrating that vitamin E functioned as an antioxidant. The liver vitamin E concentration was not changed by vitamin E supplementation to rats that did not receive CCl(4). This result indicated that vitamin E accumulated in the damaged liver. The activation of JNK, ERK1/2 and p38 MAPK took place 1.5 h after CCl(4) administration. Co-administration of alpha-tocopherol with CCl(4) did not affect these early changes in MAPKs.

Effect of α-tocopherol on in vitro maturation of bovine cumulus-oocyte complexes

This study determined: the effects of α-tocopherol on apoptotic and necrotic levels of cumulus cells after in vitro maturation of bovine oocytes; whether exposure to α-tocopherol facilitates the development of bovine enclosed oocytes to metaphase II; and the effects of this antioxidant on apoptotic and necrotic levels of granulosa cells cultured in vitro. In conclusion, supplementation with α-tocopherol on in vitro maturation of bovine oocytes has a detrimental effect on the ability of oocytes to reach metaphase II, increasing the number of apoptotic and necrotic cumulus cells of bovine cumulus oocyte complexes (COC). This antioxidant showed a slight improvement in the viability of cultured granulosa cells at a concentration of 100 µM. Key words: Bovine, oocyte maturation in vitro, antioxidant, α-tocopherol

Mechanisms of Ligand Transfer by the Hepatic Tocopherol Transfer Protein

alpha-Tocopherol is a member of the vitamin E family that functions as the principal fat-soluble antioxidant in vertebrates. Body-wide distribution of tocopherol is regulated by the hepatic alpha-tocopherol transfer protein (alphaTTP), which stimulates secretion of the vitamin from hepatocytes to circulating lipoproteins. This biological activity of alphaTTP is thought to stem from its ability to facilitate the transfer of vitamin E between membranes, but the mechanism by which the protein exerts this activity remains poorly understood. Using a fluorescence energy transfer methodology, we found that the rate of tocopherol transfer from lipid vesicles to alphaTTP increases with increasing alphaTTP concentration. This concentration dependence indicates that ligand transfer by alphaTTP involves direct protein-membrane interaction. In support of this notion, equilibrium analyses employing filtration, dual polarization interferometry, and tryptophan fluorescence demonstrated the presence of a stable alphaTTP-bilayer complex. The physical association of alphaTTP with membranes is markedly sensitive to the presence of vitamin E in the bilayer. Some naturally occurring mutations in alphaTTP that cause the hereditary disorder ataxia with vitamin E deficiency diminish the effect of tocopherol on the protein-membrane association, suggesting a possible mechanism for the accompanying pathology.

Effect of α-tocopherol on pro-oxidant and antioxidant enzyme status in radiation-treated oral squamous cell carcinoma

The relationships between alpha-tocopherol, pro-oxidant and antioxidant enzyme status, and radiation toxicity were studied in stage II, III, and IVA oral squamous cell carcinoma patients. The low levels of malondialdehyde and increased activities of antioxidant enzymes were correlated with decreased oxidative stress by alpha-tocopherol in oral cancer patients treated with radiotherapy. The objective of the present study was to evaluate the effect of alpha-tocopherol on oxidant-antioxidant enzyme status in oral squamous cell carcinoma patients treated with radiotherapy. The study included three groups with histologically confirmed oral squamous cell carcinoma patients (untreated), and they were further divided into two groups, viz., one consisting of patients who underwent radiotherapy alone (radiotherapy was given at the dosage of 6000 cGy in five fractions per week for a period of 6 weeks); and the other group treated with radiotherapy plus alpha-tocopherol supplementation (alpha-tocopherol was supplemented at a dosage of 400 IU/day) for the entire period of radiotherapy. A significant decrease ( P < 0.001) in malondialdehyde levels and increase in activities of antioxidant enzymes ( P < 0.001) in hemolysate were noticed in patients treated with radiotherapy and simultaneously supplemented with alpha-tocopherol when compared to radiation-treated patients. It was seen that alpha-tocopherol played a role in protecting against the damage caused by irradiation in oral squamous cell carcinoma patients treated with radiotherapy, by enhancing the antioxidant enzyme status and reducing the pro-oxidant status.

Effects of α-Tocopherol on Oxidative Status and Metabolic Profile in Overweight Women

Despite extensive research, the effects of alpha-tocopherol supplementation remain controversial. Few studies have been focused on obese and overweight people. We examined the effects of alpha-tocopherol (AT) on the oxidative status and metabolic profile in overweight women. Sixteen overweight women between the ages of 40-60 years old, received AT, 800 IU/day during 12 weeks, followed by a 6-week washout period. Blood samples were taken at the beginning and then every 6 weeks until the end of the study. AT, retinol, malondialdehyde (MDA), total antioxidant status (TAS), selenium-dependent glutathione peroxidase (GPx) and CuZn-superoxide dismutase (SOD) were quantified to evaluate the oxidative stress. The metabolic profile was estimated by measuring glycated hemoglobin (HbA1c) in erythrocytes and glucose, phosphate, magnesium, lipid and lipoprotein concentrations in serum. Under AT administration HbA1c, serum- MDA levels and erythrocyte GPx activity were markedly reduced. TAS, AT and Mg2+ concentrations in serum and SOD activity in erythrocytes were higher after AT treatment. Body weight; glucose, lipid and retinol concentrations, or blood cells count were unchanged. Lipid peroxidation was considerably reduced in AT treated women and also improved serum antioxidant status was observed, but the imbalanced response between erythrocyte SOD and GPx activities could affect normal response to oxidative stress.

Effect of α-tocopherol on in vitro culture of bovine embryos

Bovine oocytes were matured and fertilised under 5% CO2. Presumptive zygotes were co-cultured in synthetic oviductal fluid droplets, supplemented with either 0 (control), 25, 50, 100, or 200 µM of α-tocopherol. Blastocyst development rates were significantly influenced (P &lt; 0.05) by the level of antioxidant in the culture media. Control showed a blastocyst yield of 18.46, 21.11, 27.92, and 31.66%, respectively, at α25; α50 and α100. Blastocyst yield for α200 was severely decreased, to 8.01%. An increase in overall IVF results was also observed as the concentration of α-tocopherol increased (control, 14.21%; α25, 14.35%; α50, 19.52%; α100, 21.11%), decreasing to 5.75% for the concentration of α200. The present study clearly demonstrates that α-tocopherol at a concentration of 100 µM significantly improves the proportion of oocytes that develop to the blastocyst stage. Key words: Antioxidant, α-tocopherol, reactive oxygen species, bovine, embryo