Plasma Α-tocopherol Levels Research Articles

Prolonged, low dose α-tocopherol therapy counteracts intercellular cell adhesion molecule-1 activation

Background: Up-regulation of ICAM-1 at the vascular endothelial level is one of the most important promoters in the slow progression of a healthy vessel to an atherosclerotic one. The current study aimed to evaluate whether low dose of the antioxidant α-tocopherol affects the circulating soluble (s) ICAM-1 in healthy subjects. Methods: Either α-tocopherol E (50 I.U./day) or placebo was randomly, double-blindly given to 39 healthy male volunteers (mean age 41.6±5.9 years) over a period of 20 weeks. Results: At the baseline, sICAM-1 levels were inversely correlated with α-tocopherol concentrations ( r=−0.525, p<0.0001). Twenty weeks of α-tocopherol supplementation ( n=20 subjects) significantly decreased the circulating sICAM-1 levels (from 149.2±18.4 to 131.5±17.2 μg l −1, p<0.004) while it increased the α-tocopherol concentrations (from 25.8±5.0 to 31.2±5.7 μmol l −1, p<0.003). No significant changes in plasma sICAM-1 and α-tocopherol levels were observed in placebo-treated subjects ( n=19). In actively treated subjects, changes in circulating sICAM-1 were inversely correlated with changes in α-tocopherol concentrations ( r=−0.597, p=0.005). Conclusions: Plasma sICAM-1 concentrations are stable in healthy subjects over a period of 20 weeks while they significantly decreased with low dose of α-tocopherol. Thus, antioxidant vitamins are likely to counteract with endothelial changes that could potentially trigger the atherogenetic process.

Effect of T-2 toxin on in vivo lipid peroxidation and vitamin E status in mice

The effects of an acute administration of T-2 toxin on vitamin E status and the corresponding degree of lipid peroxidation, as determined by the plasma and organ content of malondialdehyde (MDA), was studied in mice. The effects of T-2 toxin administration on the body weight and weights of liver, spleen and thymus were also assessed. T-2 toxin was administered in doses ranging from 1 to 6.25 mg/kg body weight, depending on the experiment, while the dietary content of vitamin E ranged from near 0 to 5000 IU/kg. There was a significant decrease in vitamin E content of plasma after the administration of the toxin with the concentrations remaining low for periods as long as 48–72 h. MDA content of liver increased significantly after 24–48 h of toxin administration in contrast to the controls. However, MDA levels returned to the control range after 72 h. The concentrations of MDA in liver were inversely related to the vitamin E content of the diet, and were always higher for the toxin-treated animals (significant linear regression between MDA content of liver and the log10 of vitamin E content of the diet). Weights of spleen and thymus decreased after T-2 toxin administration; however, the weight of liver either increased or did not change in the different experiments. In conclusion, T-2 toxin treatment of mice increased lipid peroxidation in the liver as measured by MDA production. This process was maximal after 48 h of T-2 challenge, and decreased thereafter. Plasma α-tocopherol levels decreased as soon as 6 h after the toxin challenge, while MDA did not increase until there was a severe depletion of vitamin E. These changes were accompanied by decrease in weight of spleen and thymus.

Comparison of Gas Chromatography–Mass Spectrometry and Liquid Chromatography–Tandem Mass Spectrometry Methods to Quantify α-Tocopherol and α-Tocopherolquinone Levels in Human Plasma

Two mass spectrometric methods were established for the quantitative analyses of α-tocopherol (TH) and its oxidation product α-tocopherolquinone (TQ) in human plasma. Both methods make use of isotopically labeled internal standards of different levels of deuteration (d3-TH and d6-TQ). Plasma (100 μl) was saponified in the presence of a mixture of antioxidants, and then TH and TQ were extracted with hexane. With the GC-MS method, the analytes were first converted into O-trimethylsilyl derivatives before analysis in the selective ion monitoring mode. The derivatization procedure led to the quantitative conversion of TQ into the O-trimethylsilyl derivative of tocopherolhydroquinone, giving rise to a more stable molecule with less fragmentation than for TQ. The increased stability of the molecule resulted in an enhanced contribution of the base peak to the total observed ions and therefore an increased sensitivity of the base peak for quantification. With the liquid chromatography–tandem mass spectrometry (LC-MS/MS) method, TH and TQ were detected by multiple reaction monitoring after positive electrospray ionization. The GC-MS and LC-MS/MS methods showed nearly the same accuracy (>95%) and the same within-day precisions, with less than 5 and 10% for TH and TQ, respectively. The between-day precision and the limit of quantification for TQ in plasma were better by LC-MS/MS (4%; 3 nM) than by GC-MS (21%; 10 nM). Analysis and method validation were carried out with plasma samples obtained from a male volunteer pre- and postexercise. Both techniques showed that the ratio of TQ/TH was elevated by 35% immediately after exercise and had returned to basal levels when measured 24 h later.

Effect of atorvastatin on LDL oxidation and antioxidants in normocholesterolemic type 2 diabetic patients

Background: Oxidative stress in diabetes increases lipid peroxidation, which stimulates the development of atherosclerosis. Methods: We investigated in a 3-month placebo-controlled study with 19 normocholesterolemic type 2 diabetic patients whether treatment with 10-mg atorvastatin influenced antioxidants and reduced LDL oxidizability, assessed by in vitro production of conjugated dienes after copper-induced LDL oxidation. Results: The lag phase, as a measure of the resistance of LDL to oxidation, did not change (62.8±8.2 respectively 59.6±9.7 min, p=n.s.), while conjugated dienes decreased (512±74 respectively 487±50 nmol, p=0.012). Plasma α-tocopherol and ubiquinol levels decreased, while their ratios to LDL cholesterol remained stable. Conclusions: Atorvastatin favourably influences some parameters of LDL oxidation. Whether this effect is clinically relevant remains to be determined.

Effect of a moderately energy-restricted diet on obese patients with fatty liver

The effects of a moderately energy-restricted (25 kcal/kg) diet on liver-function tests, anthropometric measurements, mononuclear-cell phospholipid fatty acid, lymphocyte blastogenesis, and plasma prostaglandin E 2 and α-tocopherol levels were observed at weeks 0, 8, and 24 in 14 obese patients with fatty liver. Serum aminotransferase levels were improved significantly, with decreases in the body mass index and waist circumference. Decreases in energy intake from carbohydrate and increases in intake of vitamin A, vitamin C, and vegetables were observed at week 24. In mononuclear-cell phospholipids, linoleic acid (18:2ω 6), which was significantly lower in patients than in controls at week 0, was increased at week 24. In contrast, arachidonic acid was decreased. Plasma prostaglandin E 2 levels were significantly lower in patients than in controls at week 0 and increased at week 24. The mononuclear-cell response for phytohemagglutinin correlated with 18:2ω 6 in mononuclear-cell phospholipids ( r = 0.692, P < 0.01). Improvement of the serum alanine-aminotransferase level correlated with an increase in the plasma α-tocopherol level ( r = −0.667, P < 0.01) and increases in consumption of vitamin A, ω 3 polyunsaturated fatty acids, and vegetables. These findings suggest that a hypoenergetic diet rich in ω 3 polyunsaturated fatty acids and antioxidants might be beneficial for obese patients with fatty liver.

Enhanced level of n-3 fatty acid in membrane phospholipids induces lipid peroxidation in rats fed dietary docosahexaenoic acid oil

The effect of dietary docosahexaenoic acid (DHA, 22:6n-3) oil with different lipid types on lipid peroxidation was studied in rats. Each group of male Sprague–Dawley rats was pair fed 15% (w/w) of either DHA-triglycerides (DHA-TG), DHA-ethyl esters (DHA-EE) or DHA-phospholipids (DHA-PL) for up to 3 weeks. The palm oil (supplemented with 20% soybean oil) diet without DHA was fed as the control. Dietary DHA oils lowered plasma triglyceride concentrations in rats fed DHA-TG (by 30%), DHA-EE (by 45%) and DHA-PL (by 27%), compared to control. The incorporation of dietary DHA into plasma and liver phospholipids was more pronounced in the DHA-TG and DHA-EE group than in the DHA-PL group. However, DHA oil intake negatively influenced lipid peroxidation in both plasma and liver. Phospholipid peroxidation in plasma and liver was significantly higher than control in rats fed DHA-TG or DHA-EE, but not DHA-PL. These results are consistent with increased thiobarbituric acid reactive substances (TBARS) and decreased α-tocopherol levels in plasma and liver. In addition, liver microsomes from rats of each group were exposed to a mixture of chelated iron (Fe 3+/ADP) and NADPH to determine the rate of peroxidative damage. During NADPH-dependent peroxidation of microsomes, the accumulation of phospholipid hydroperoxides, as well as TBARS, were elevated and α-tocopherol levels were significantly exhausted in DHA-TG and DHA-EE groups. During microsomal lipid peroxidation, there was a greater loss of n-3 fatty acids (mainly DHA) than of n-6 fatty acids, including arachidonic acid (20:4n-6). These results indicate that polyunsaturation of n-3 fatty acids is the most important target for lipid peroxidation. This suggests that the ingestion of large amounts of DHA oil enhances lipid peroxidation in the target membranes where greater amounts of n-3 fatty acids are incorporated, thereby increasing the peroxidizability and possibly accelerating the atherosclerotic process.

Antioxidant Status in Patients with Cystic Fibrosis

Background: The aim of the study was to assess the antioxidant status in cystic fibrosis (CF) patients compared to healthy controls. In order to determine the influence of nutrition on the level of the antioxidants, nutrient intake was also monitored in both groups at the time of the antioxidant assessment. Subjects and Methods: The authors measured the serum malondialdehyde levels in children with CF, n = 21; 9 females and 12 males, mean age: 8.71 years (6–12 years) and compared these values to the levels found in age-matched healthy control subjects, n = 24; 13 females and 11 males, mean age: 8.33 years (6–12 years). In order to assess the antioxidant status, catalase and superoxide dismutase activities in washed erythrocytes, glutathione peroxidase activity of heparinized whole blood and serum ascorbic acid, α-tocopherol and retinol levels were measured. Total antioxidant status (TAS) was also tested. The patients with CF received vitamin supplementation in doses prescribed in international guidelines (α-tocopherol: <10 years 100 mg daily, >10 years 200 mg daily, retinol: 2.5 mg daily, ascorbic acid: 100–200 mg daily). Results: Plasma levels of malondialdehyde were significantly higher (p < 0.05), superoxide dismutase activities were significantly lower (p < 0.05) in patients with cystic fibrosis. There were no significant differences in catalase, glutathione peroxidase activities and TAS levels between CF patients and control group. Plasma ascorbic acid, α-tocopherol and retinol levels were within normal limits in both groups. Conclusion: On the basis of the present results this regime failed to provide sufficient antioxidant protection. Therefore, the authors suggest that the daily dose of these antioxidants should be either increased or to administer in parenteral route to patients with severe form of the disease.

Associations of Plasma Aflatoxin B1-Albumin AdductLevel With Plasma Selenium Level and GeneticPolymorphisms of Glutathione S-Transferase M1 and T1

Mortality from hepatocellular carcinoma (HCC) is extraordinarily high in Matzu, an island off the coast of Southeastern China. To investigate factors associated with plasma aflatoxin B1 (AFB1)-albumin adduct level, we studied 304 healthy adult residents from Matzu. AFB1-albumin adducts were determined by competitive enzyme-linked immunosorbent assay, hepatitis B surface antigen status by enzyme immunoassay, genotypes of glutathione S-transferase (GST) M1 and T1 by polymerase chain reaction, plasma selenium by atomic absorption spectrometry, and plasma retinol, α-tocopherol, α-carotene, and β-carotene levels by high-performance liquid chromatography. Men had higher AFB1-albumin adduct levels than women. GSTM1-nonnull and GSTT1-null genotypes and low plasma selenium level were significantly associated with an increased level of AFB1-albumin adducts among men, whereas age was significantly correlated with adduct level among women. High intake of fermented beans was associated with an increased adduct level among men and women. The inverse associations between plasma selenium level and AFB1-albumin adducts were statistically significant among those with null genotypes of GSTM1 and GSTT1, but not among the nonnull genotypes. This study provides insight into the dietary and genetic factors influencing AFB1-albumin adduct formation in an isolated population with high liver cancer mortality.

Vitamins C and E protect isolated cardiomyocytes against oxidative damage

There is considerable evidence that oxygen free radicals are involved in reperfusion injury of ischemic myocardium. Epidemiologic studies showed an inverse correlation between plasma levels of α-tocopherol (vitamin E) and ascorbic acid (vitamin C) and mortality from ischemic heart disease. The present study examines the influence of both vitamins on the toxic effects of singlet oxygen on isolated rat cardiomyocytes. Freshly isolated cardiomyocytes from adult rats were exposed to singlet oxygen which was generated by photoactivation of the photosensitive dye rose bengal (10 −7 M). This procedure induced irreversible hypercontracture in about 95% of rod-shaped cardiomyocytes within 15 min after onset of photoactivation of rose bengal. Pretreatment with vitamin C (10 −5 to 10 −2 M) or E (10 −6 to 10 −3 M) reduced the number of hypercontracted cells after exposure to singlet oxygen in a concentration-dependent manner. Simultaneous application of both vitamins (vitamin E 10 −6 M plus vitamin C 10 −5 M or vitamin E 10 −5 M plus vitamin C 10 −4 M) revealed a marked overadditive protective effect against oxidative damage as compared with the single application of each vitamin. Our data show that α-tocopherol and ascorbic acid exert direct protective actions on isolated cardiomyocytes against oxidative damage and provide an overadditive effect if administered simultaneously.

Immune response to influenza vaccine in healthy elderly: lack of association with plasma β-carotene, retinol, α-tocopherol, or zinc

Immunity and nutritional status are compromised with age, yet the relationship between them is unclear. Immune responses and plasma micronutrient levels of 61 healthy elderly (mean 81 years) and 27 young (mean 27 years) were assessed before and after immunization with trivalent influenza vaccine (FLU). FLU-induced proliferation and IFN-γ levels of elderly were lower than young before and after immunization. Proliferation and IFN-γ levels increased after immunization of young, but not elderly. FLU-induced IL-6 and IL-10 levels did not change after immunization of either group. While antibody titers to all three FLU components increased after vaccination of young and elderly, post-vaccination titers of elderly were lower than young. Although plasma retinol and zinc levels of young and elderly were similar before and after vaccination, elderly had higher plasma β-carotene and α-tocopherol levels at both assessments that increased after vaccination. Importantly, plasma micronutrient levels were comparable for elderly with or without intact (titers ≥40 and fourfold rise post-vaccination) antibody responses after vaccination. These results suggest that differences in these plasma micronutrients (1) are not required to observe decreased FLU responses of healthy elderly compared to young and (2) are not associated with differences in antibody responses among healthy elderly.

Effects of lisinopril and amlodipine on antioxidant status in experimental hypertension

The objective of this investigation was to compare changes in antioxidant status (together with other metabolites relevant to hypertension) in plasma and cardiac tissue from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY), following 8 weeks of treatment with lisinopril (angiotensin converting enzyme inhibitor) or amlodipine (Ca 2+ channel antagonist) respectively. There was no significant difference in the levels of total antioxidant capacity, retinol, urea, albumin or triglyceride in plasma from SHR or WKY rats, with or without lisinopril or amlodipine treatment. However in SHR rats, levels of α-tocopherol were substantially reduced in both plasma (−54% WKY, P<0.01) and cardiac tissue (−43% WKY, P<0.05). Treatment with lisinopril ameliorated reduced levels of plasma α-tocopherol in SHR rats, but not in cardiac tissue. Amlodipine treatment had no effect on α-tocopherol levels in plasma or cardiac tissue in SHR rats. In SHR rats total cholesterol levels were significantly lower thanWKY controls (−36%, P<0.001). This effect was reversed in lisinopril treated SHR rats (+27%, P<0.01). Plasma high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol were reduced in untreated SHR rats ( P<0.025) when compared to WKY controls; neither lisinopril nor amlodipine treatment significantly altered these parameters. These findings suggest possible alternative mechanisms of action for lisinopril, and reinforce its use in hypertensive patients or patients with left ventricular hypertrophy.

Relationship between classic risk factors, plasma antioxidants and indicators of oxidant stress in angina pectoris (AP) in Tehran

Cardiovascular disease (CVD) in general seems to be the leading cause of death in the Eastern Mediterranean Region (EMR) including Iran. This may be due to classic risk factors such as high triglyceride (TG), high total cholesterol (TC), and low levels of high density lipoprotein cholesterol (HDL-C). The impact of antioxidants as potentially protective risk factors against early coronary heart disease (CHD) is unknown in Iran. Therefore, relationships between angina and plasma antioxidants and indicators of lipid peroxidation were investigated in a case-control study. In this study, 82 cases of previously undiagnosed angina pectoris (AP), identified by a modified WHO Rose chest pain questionnaire and verified by electrocardiography during treadmill exercise testing, were compared with 146 controls selected from the same population of over 4000 male civil servants aged 40–60 years. Subjects with AP declared significantly less physical activity and had higher serum TG [means (S.E.M.) 2.32 (0.18) versus 1.61 (0.07) mmol/l] but lower HDL-C [1.01 (0.04) versus 1.18 (0.03) mmol/l] than age-matched controls. Levels of total serum cholesterol, low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) [Lp(a)] were not significantly different between the two groups, while the ratio of LDL-C/HDL-C was significantly higher [4.51 (0.23) versus 3.54 (0.11)] for subjects with AP than for the controls. There was no significant difference in plasma levels of α-tocopherol, vitamin C, α- and β-carotene. However, retinol [1.90 (0.06) versus 2.09 (0.05)] and β-cryptoxanthin [0.398 (0.04) versus 0.467 (0.03)] were significantly lower in AP. Furthermore, angina cases exhibited a higher index of lipid peroxidation than controls (e.g. malondialdehyde, MDA; 0.376 (0.010) versus 0.337 (0.009) μmol/l). On multiple logistic regression analysis, retinol with odds ratio (OR) of 0.644 [95% confidence interval (CI; 0.425–0.978)], β-cryptoxanthin, with an OR of 0.675 (CI; 0.487–0.940), oxidation indices, MDA with OR of 1.612 (95% CI; 1.119–2.322) and LDL-C/HDL-C ratio with OR of 2.006 (95% CI; 1.416–2.849) showed the most significant independent associations with AP in this group of Iranians. In conclusion, the state of lipid peroxidation as well as the status of special antioxidants may be co-determinants of AP in Iran, in parallel with the influence of classical risk factors for cardiovascular disease.

Vitamin E in relation to lipid peroxidation in experimental septic shock

Lipid peroxidation and antioxidant balance in the body is a crucial factor in the pathophysiology of various diseases. This study investigates the circulatory α-tocopherol levels and its relationship with 8-iso-prostaglandin F2α(8-iso-PGF2α), a non-enzymatic and, 15-keto-13,14-dihydro-PGF2α(15-K-DH-PGF2α), a cyclooxygenase catalysed oxidation product of arachidonic acid in experimental septic shock in pigs. A steady decrease in α-tocopherol levels in plasma was observed in both survivor and non-survivor animals. A simultaneous increase of oxidative injury indicator, plasma 8-iso-PGF2αwas seen in both groups but with a different fashion. 8-Iso-PGF2αlevels increased steadily in the animals that died during the experiment. An early and rapid increase of plasma 15-K-DH-PGF2α, an inflammatory response indicator, was also observed in all animals. There was a significant difference in the kinetics of decrement of α-tocopherol levels and a concomitant increase in 15-K-DH-PGF2αlevels among the non-survivors. Thus, a successive disappearance of circulatory vitamin E in conjunction with the surge of plasma isoprostanes and prostaglandins impairs the oxidant-antioxidant balance in favour of the former and may possibly have an effect on the survivality during experimental porcine septicaemia.

Biomarkers of oxidative stress study: are plasma antioxidants markers of CCl 4 poisoning?

Antioxidants in the blood plasma of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. For this initial study an animal model of CCl 4 poisoning was studied. The time (2, 7, and 16 h) and dose (120 and 1200 mg/kg, intraperitoneally)-dependent effects of CCl 4 on plasma levels of α-tocopherol, coenzyme Q (CoQ) , ascorbic acid, glutathione (GSH and GSSG), uric acid, and total antioxidant capacity were investigated to determine whether the oxidative effects of CCl 4 would result in losses of antioxidants from plasma. Concentrations of α-tocopherol and CoQ were decreased in CCl 4-treated rats. Because of concomitant decreases in cholesterol and triglycerides, it was impossible to dissociate oxidation of α-tocopherol and the loss of CoQ from generalized lipid changes, due to liver damage. Ascorbic acid levels were higher with treatment at the earliest time point; the ratio of GSH to GSSG generally declined, and uric acid remained unchanged. Total antioxidant capacity showed no significant change except for 16 h after the high dose, when it was increased. These results suggest that plasma changes caused by liver malfunction and rupture of liver cells together with a decrease in plasma lipids do not permit an unambiguous interpretation of the results and impede detection of any potential changes in the antioxidant status of the plasma.

Improvement of lipid stability of rabbit meat by vitamin E and C administration

The effect of administering vitamins E (E50 or E200: 50 or 200 mg kg diet) and C (C500 or C1000: 500 or 1000 mg l−1 water) singly and in combination was verified on plasma and muscle levels of α-tocopherol and the oxidative stability of rabbit meat during display. Six groups of 10 hybrid males were fed experimental diets from 35 to 85 days of age. Productive performance and carcass drip loss were also recorded. Performance was unaffected by treatments, but drip loss was improved by simultaneous administration of the two antioxidants. The α-tocopherol levels in plasma and muscle were significantly higher in animals which simultaneously ingested the highest amounts of the two vitamins, and the oxidative processes (TBA-RS values) of their meat during storage were lower. The results confirm the synergistic action of ascorbate and the benefit of using high levels of the two vitamins to prevent oxidative stress during meat processing and storage. © 2000 Society of Chemical Industry

Relative Effects of alpha- and gamma-Tocopherol on Low-Density Lipoprotein Oxidation and Superoxide Dismutase and Nitric Oxide Synthase Activity and Protein Expression in Rats.

BACKGROUND: Increasing evidence suggests that vitamin E prevents the progression of atherosclerosis by inhibiting platelet aggregation, monocyte adhesion, and improving plaque stability and vasomotor function. Recently, controversy has arisen as to the relative effects of alpha- and gamma-tocopherol in modulating some mediators of atherosclerosis. METHODS AND RESULTS: We examined the effects of alpha- and gamma-tocopherol on constitutive nitric oxide synthase (cNOS) and superoxide dismutase (SOD) activity and protein expression in rats. Sprague-Dawley rats were fed regular chow or chow mixed with alpha- or gamma-tocopherol (100 mg/kg/day) for 7 to 10 days. Plasma alpha- and gamma-tocopherol levels, low-density lipoprotein (LDL) oxidation, and cNOS and SOD activity and protein expression were measured. Plasma alpha-tocopherol levels were significantly increased (eP <.01 vs control), but gamma-tocopherol levels fell (P <.01 vs control) in rats fed alpha-tocopherol. Plasma gamma-tocopherol levels were increased (P <.01 vs control), and alpha-tocopherol levels did not change in rats fed gamma-tocopherol. Both alpha- and gamma-tocopherol feeding decreased the rate of LDL oxidation induced by phorbol 12-myristate 13-acetate (PMA)-stimulated leukocytes (P <.01 vs control). Both alpha- and gamma-tocopherol increased SOD activity in plasma and arterial tissues as well as Mn SOD and Cu/Zn SOD protein expression in arterial tissues (all P <.01 vs control). gamma-Tocopherol was more potent than alpha-tocopherol in all these effects (P <.05). Both a- and gamma-tocopherol increased NO generation and cNOS activity (all P <.05 vs control). However, only gamma-tocopherol increased cNOS protein expression. CONCLUSIONS: These observations indicate that whereas both alpha- and gamma-tocopherol exert important effects on determinants of oxidationand vasomotor function, effects of dietary gamma-tocopherol supplementation in vivo are less pronounced than those of gamma-tocopherol supplementation.

Effect of dialysis on oxidative stress in uraemia

It has been postulated that dialysis of patients with chronic renal failure (CRF) is associated with increased lipid peroxidation which may contribute to vascular and other complications of the syndrome. In the present study, a specific and precise technique [ferrous oxidation in xylenol orange (FOX) assay] was used to measure plasma lipid hydroperoxides (ROOHs) in three groups of uraemic patients. Patients were either studied before starting dialysis (n= 12) or on continuous ambulatory peritoneal dialysis (CAPD, n= 12) or haemodialysis (HD, n= 36) and compared to healthy controls (n=20). Plasma ROOHs were markedly elevated in HD patients compared with the controls (7.01±2.9 µM versus 4.25±2.05 µM; P < 0.005, Mann-Whitney test). Plasma ROOH concentrations in the CAPD patients were increased but not significantly higher than controls (5.36±3.56 µM versus 4.25±2.05 µM). By contrast, no differences in ROOH levels were found between controls and predialysis patients. There was no difference in plasma thiobarbituric acid reactive substances (TBARS)between control and the three CRF groups. Absolute and cholesterol standardised plasma α-tocopherol levels were lower in the patients (whether they were on dialysis or not) than in the controls (18.62±6.88 µM versus 22.73±5.33 µM; P < 0.01 and 1.99±1.88 µM/mM versus 5.25±1.0 µM/mM; P < 0.0005, respectively). This study provides direct evidence that enhanced oxidative stress in CRF patients is related to the dialysis treatment rather than the disease itself. Further studies will be necessary to establish the relationships between plasma measures of oxidative stress and cardiovascular complications in CRF patients under dialysis and whether treatment with antioxidants may reduce oxidative stress or reverse adverse effects associated with dialysis.

An Assessment of Appropriate Vitamin E Content in Fish Oil Capsules as Estimated by Lipid Peroxide and Vitamin E Levels in Human Blood.

To assess the appropriate content of vitamin E (VE) in fish oil capsules, we determined lipid peroxide and VE levels in human blood after hyperlipidemic female volunteers had heed given purified eicosapentaenoic acid (EPA) ethyl ester (90% purity) in capsules along with a controlled basal diet. A two consecutive 7-day menu cycle was used, and the capsules were taken with the second 7-day menu. The basal diet was based on the recommended dietary allowances for female Japanese with light physical activities. The fat energy density of the diet was 25%, and the cholesterol intake was less than 300mg per day. Each volunteer ingested nine capsules (2.43g of EPA ethyl ester in total) daily in three divided doses, and a daily total of 5.4mg of all-rac-α-tocopherol (4mg RRR-α-tocopherol equivalent) from the capsules. Blood was collected before and after 1 and 2 weeks of the basal diet periods. Triacylglycerol and total cholesterol concentrations in plasma were determined, and plasma lipid peroxide levels as estimated by thiobarbituric acid reactive substances (TBARS) and water-soluble fluorescent substances (WSF) were also measured. In addition, α-tocopherol levels in plasma, red blood cells (RBC), and platelets were analyzed. The plasma total cholesterol concentration decreased significantly after supplementation with the capsules, but that of triacylglycerol did not change significantly. The TBARS values expressed as plasma concentration and in terms of plasma lipid levels did not change significantly in each case. An amelioration of plasma lipid levels effectively lowered the plasma concentration of WSF. The plasma α-tocopherol concentration did not change significantly with the treatment with the capsules, although the concentration decreased significantly on the controlled basal diet with lower energy but without the supplementation. Neither the α-tocopherol content in RBC nor that in platelets changed significantly during the test period. In conclusion, the VE content in the EPA capsules appears to be sufficient to provide adequate antioxidant protection during the short period of the experiment. An assessment of appropriate VE content in fish oil capsules is discussed by comparing the current data with those reported elsewhere.

Effect of Dietary Vitamin E on the Oxidative Stability of Raw and Cooked Rabbit Meat

The effect of dietary α-tocopheryl acetate supplementation (200 mg/kg diet) on plasma and muscle levels of α-tocopherol and the oxidative stability of raw and cooked rabbit meat was determined. Two groups of 20 male hybrid rabbits were fed the experimental diets from 35 to 80 days of age. Feed intake, live weight, feed efficiency and qualitative traits of the carcass and meat were recorded. The α-tocopherol levels in plasma and muscle were significantly higher ( p≤0·01) in the supplemented group, which also showed an increase in oxidative stability in both raw and cooked meat. The higher α-tocopherol level improved the physical traits of the meat, significantly reducing shear value and increasing water-holding capacity; n-3 fatty acids in raw and cooked meat increased ( p≤0·05) and the thrombogenic index decreased ( p≤0·05). Dietary vitamin E did not influence weight gain, feed intake and dressing yield.

Pretreatment of Young Pigs with Vitamin E Attenuates the Elevation in Plasma Interleukin-6 and Cortisol Caused by a Challenge Dose of Lipopolysaccharide

The effect of a short-term, high-dose intramuscular injection of d-α-tocopherol was studied in pigs given a challenge dose of lipopolysaccharide (LPS). Twenty-four pigs surgically fitted with jugular catheters were used in a 2 × 2 factorial design. Pigs received either 0 or 600 mg d-α-tocopherol by intramuscular injection for 3 d before receiving an intraperitoneal injection of saline containing either 0 or 5 μg/kg body weight Escherichia coli LPS. Blood was collected from indwelling jugular catheters at 0, 1, 2, 4, 6, 8, 12 and 24 h after injection of LPS. Plasma α-tocopherol levels were 13-fold greater (P < 0.01) at time 0 in pigs pretreated with 600 mg d-α-tocopherol (9.9 ± 1.3 mg/L) than in those not treated with d-α-tocopherol (0.74 ± 0.09 mg/L). Injection of LPS increased (P < 0.05) plasma levels of interleukin-6 (IL-6) and cortisol at 2-h postinjection, regardless of vitamin E treatment. However, pigs that received α-tocopherol before the LPS challenge had substantially lower (P < 0.05) peak levels of IL-6 and cortisol than pigs not receiving α-tocopherol. These results suggest that supplementation with a surfeit level of vitamin E reduces the response of pigs to endotoxin.