Urinary oxidized, but not enzymatic vitamin E metabolites are inversely associated with measures of glucose homeostasis in middle-aged healthy individuals.

BACKGROUND & AIMS: Damage induced by lipid peroxidation has been associated with impaired glucose homeostasis. Vitamin E (α-tocopherol, α-TOH) competitively reacts with lipid peroxyl radicals to mitigate oxidative damage, and forms oxidized vitamin E metabolites. Accordingly, we aimed to investigate the associations between α-TOH metabolites (oxidized and enzymatic) in both circulation and urine and measures of glucose homeostasis in the general middle-aged population. METHODS: This cross-sectional study was embedded in the population-based Netherlands Epidemiology of Obesity (NEO) Study. α-TOH metabolites in blood (α-TOH and α-CEHC-SO3) and urine [sulfate (SO3) and glucuronide (GLU) of both α-TLHQ (oxidized) and α-CEHC (enzymatic)] were quantified by liquid chromatography coupled with tandem mass spectrometry (LC/MS-MS). Measures of glucose homeostasis (HOMA-B, HOMA-IR, Insulinogenic index and Matsuda index) were obtained from fasting and postprandial blood samples. Multivariable linear regression analyses were performed to assess the associations of α-TOH metabolites and measures of glucose homeostasis. RESULTS: We included 498 participants (45% men) with mean (SD) age of 55.8 (6.1) years who did not use glucose-lowering medication. While blood α-TOH was not associated with measures of glucose homeostasis, urinary oxidized metabolites (α-TLHQ-SO3/GLU) were associated with HOMA-IR and Matsuda index. For example, a one-SD higher α-TLHQ-SO3 was associated with 0.92 (95% CI: 0.87, 0.97) fold lower HOMA-IR and 1.06 (1.01, 1.11) fold higher Matsuda index, respectively. Similar results were obtained for the urinary α-TLHQ to α-CEHC ratio as a measure of oxidized-over-enzymatic conversion of α-TOH. CONCLUSION: Higher urinary levels of oxidized α-TOH metabolites as well as higher oxidized-to-enzymatic α-TOH metabolite ratio, but not circulating α-TOH or enzymatic metabolites, were associated with lower insulin resistance. Rather than circulating α-TOH, estimates of the conversion of α-TOH might be informative in relation to health and disease.

Alcohol consumption and serum metabolite concentrations in young women.

PURPOSE: Alcohol consumption is an established breast cancer risk factor, though further research is needed to advance our understanding of the mechanism underlying the association. We used global metabolomics profiling to identify serum metabolites and metabolic pathways that could potentially mediate the alcohol-breast cancer association. METHODS: A cross-sectional analysis of reported alcohol consumption and serum metabolite concentrations was conducted among 211 healthy women 25-29 years old who participated in the Dietary Intervention Study in Children 2006 Follow-Up Study (DISC06). Alcohol-metabolite associations were evaluated using multivariable linear mixed-effects regression. RESULTS: Alcohol was significantly (FDR p < 0.05) associated with several serum metabolites after adjustment for diet composition and other potential confounders. The amino acid sarcosine, the omega-3 fatty acid eicosapentaenoate, and the steroid 4-androsten-3beta,17beta-diol monosulfate were positively associated with alcohol intake, while the gamma-tocopherol metabolite gamma-carboxyethyl hydroxychroman (CEHC) was inversely associated. Positive associations of alcohol with 2-methylcitrate and 4-androsten-3beta,17beta-diol disulfate were borderline significant (FDR p < 0.10). Metabolite set enrichment analysis identified steroids and the glycine pathway as having more members associated with alcohol consumption than expected by chance. CONCLUSIONS: Most of the metabolites associated with alcohol in the current analysis participate in pathways hypothesized to mediate the alcohol-breast cancer association including hormonal, one-carbon metabolism, and oxidative stress pathways, but they could also affect risk via alternative pathways. Independent replication of alcohol-metabolite associations and prospective evaluation of confirmed associations with breast cancer risk are needed.

γ-Tocopherol Is Metabolized Faster than α-Tocopherol in Young Japanese Women.

To elucidate the characteristics of γ-tocopherol metabolism, serum concentrations of α- and γ-tocopherol, and urinary excretion of their metabolites after ingestion of α- or γ-tocopherol, major isoforms in our diet, were compared. Six healthy Japanese women (age 22.7±1.7 y old, BMI 21.4±0.9) ingested 134 mg of α- or γ-tocopherol, and blood and urine were collected until 72 h later. After α-tocopherol intake, the serum concentration of α-tocopherol increased at 12-24 h, and urinary excretion of 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman (α-CEHC), an α-tocopherol metabolite, increased at 12-36 h. However, after γ-tocopherol intake, the serum concentration of γ-tocopherol increased at 6-12 h, and excretion of 2,7,8-trimethyl-2(2'-carboxyethyl)-6-hydroxychroman (γ-CEHC), a γ-tocopherol metabolite, increased at 3-12 h. The area under the curve from 0 to 72 h and serum maximal concentration of γ-tocopherol were lower than those of α-tocopherol. The time to maximal concentration of γ-tocopherol was faster than that of α-tocopherol. The ratio of urinary excretion of carboxyethyl-hydroxychroman to tocopherol intake was 2.9% for α-CEHC and 7.7% for γ-CEHC. These results revealed that γ-tocopherol is metabolized faster than α-tocopherol in healthy young women.

A Metabolomic and Lipidomic Serum Signature from Nonhuman Primates Administered with a Promising Radiation Countermeasure, Gamma-Tocotrienol.

The development of radiation countermeasures for acute radiation syndrome (ARS) has been underway for the past six decades, leading to the identification of multiple classes of radiation countermeasures. However, to date, only two growth factors (Neupogen and Neulasta) have been approved by the United States Food and Drug Administration (US FDA) for the mitigation of hematopoietic acute radiation syndrome (H-ARS). No radioprotector for ARS has been approved by the FDA yet. Gamma-tocotrienol (GT3) has been demonstrated to have radioprotective efficacy in murine as well as nonhuman primate (NHP) models. Currently, GT3 is under advanced development as a radioprotector that can be administered prior to radiation exposure. We are studying this agent for its safety profile and efficacy using the NHP model. In this study, we analyzed global metabolomic and lipidomic changes using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS) in serum samples of NHPs administered GT3. Our study, using 12 NHPs, demonstrates that alterations in metabolites manifest only 24 h after GT3 administration. Furthermore, metabolic changes are associated with transient increase in the bioavailability of antioxidants, including lactic acid and cholic acid and anti-inflammatory metabolites 3 deoxyvitamin D3, and docosahexaenoic acid. Taken together, our results show that the administration of GT3 to NHPs causes metabolic shifts that would provide an overall advantage to combat radiation injury. This initial assessment also highlights the utility of metabolomics and lipidomics to determine the underlying physiological mechanisms involved in the radioprotective efficacy of GT3.

Metabolic syndrome increases dietary α-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial.

Background: Vitamin E supplementation improves liver histology in patients with nonalcoholic steatohepatitis, which is a manifestation of the metabolic syndrome (MetS). We reported previously that α-tocopherol bioavailability in healthy adults is higher than in those with MetS, thereby suggesting that the latter group has increased requirements.Objective: We hypothesized that α-tocopherol catabolites α-carboxyethyl hydroxychromanol (α-CEHC) and α-carboxymethylbutyl hydroxychromanol (α-CMBHC) are useful biomarkers of α-tocopherol status.Design: Adults (healthy or with MetS; n = 10/group) completed a double-blind, crossover clinical trial with four 72-h interventions during which they co-ingested 15 mg hexadeuterium-labeled RRR-α-tocopherol (d6-α-T) with nonfat, reduced-fat, whole, or soy milk. During each intervention, we measured α-CEHC and α-CMBHC excretions in three 8-h urine collections (0-24 h) and plasma α-tocopherol, α-CEHC, and α-CMBHC concentrations at various times ≤72 h.Results: During the first 24 h, participants with MetS compared with healthy adults excreted 41% less α-CEHC (all values are least-squares means ± SEMs: 0.6 ± 0.1 compared with 1.0 ± 0.1 µmol/g creatinine, respectively; P = 0.002), 63% less hexadeuterium-labeled (d6)-α-CEHC (0.04 ± 0.02 compared with 0.13 ± 0.02 µmol/g creatinine, respectively; P = 0.002), and 58% less d6-α-CMBHC (0.017 ± 0.004 compared with 0.041 ± 0.004 µmol/g creatinine, respectively; P = 0.0009) and had 52% lower plasma d6-α-CEHC areas under the concentration curves [area under the curve from 0 to 24 h (AUC0-24h): 27.7 ± 7.9 compared with 58.4 ± 7.9 nmol/L × h, respectively; P = 0.01]. d6-α-CEHC peaked before d6-α-T in 77 of 80 paired plasma concentration curves. Urinary d6-α-CEHC 24-h concentrations were associated with the plasma AUC0-24 h of d6-α-T (r = 0.53, P = 0.02) and d6-α-CEHC (r = 0.72, P = 0.0003), and with urinary d6-α-CMBHC (r = 0.88, P < 0.0001), and inversely with the plasma inflammation biomarkers C-reactive protein (r = -0.70, P = 0.0006), interleukin-10 (r = -0.59, P = 0.007), and interleukin-6 (r = -0.54, P = 0.01).Conclusion: Urinary α-CEHC and α-CMBHC are useful biomarkers to noninvasively assess α-tocopherol adequacy, especially in populations with MetS-associated hepatic dysfunction that likely impairs α-tocopherol trafficking. This trial was registered at clinicaltrials.gov as NCT01787591.

Plasma phospholipase, γ-CEHC and antioxidant capacity in fibromyalgia.

OBJECTIVE: Recent studies have suggested a possible role of high levels of plasma lysophosphocholines (lysoPCs) in fibromyalgia syndrome (FMS). The aim of this study was to evaluate the content of plasma phospholipases (e.g., Platelet Activating Factor Acetyl Hydrolase [PAF-AH], secretory Phospholipase A2 [sPLA2 ], Total Antioxidant Capacity [TAOC] and 2,7,8-trimethyl-2-(2-carboxyethyl)-6-hydroxy chroman [γ-CEHC]) in FMS patients and their association with clinical status and quality of life. METHODS: Thirty-six females meeting the 2011 American College of Rheumatology criteria for the classification of FMS and thirty-four healthy females were enrolled for the study. Plasma enzyme levels were quantified using commercial enzyme-linked-immunosorbent-assay (ELISA). In order to assess the disease severity and the functional status of patients, the Fibromyalgia Impact Questionnarie (FIQ) was used. RESULTS: Higher levels of sPLA2 and lower PAF-AH and γ-CEHC were observed in the plasma of FMS patients compared to the controls. A decrease in PAF-AH and TAOC levels were found in severe FMS (S-FMS) compared to mild/slight (MS-FMS) forms. CONCLUSION: The results of the study indicate a possible involvement of phospholipases and γ-CEHC in fibromyalgia syndrome.

Comparing palm oil tocotrienol rich fraction with α-tocopherol supplementation on oxidative stress in healthy older adults.

Vitamin E is a fat-soluble compound and powerful antioxidant that have been shown to protect the cell membranes against damage caused by free radicals. Human vitamin E supplementation studies are usually limited to α-tocopherol but currently tocotrienols are also available. This study aims to compare the effects of tocotrienol rich fraction (TRF) with α-tocopherol (α-TF) supplementation on oxidative stress in healthy male and female older adults aged 50-55 years old. A total of 71 subjects both male and female aged between 50 and 55 years were divided into groups receiving placebo (n = 23), α-TF (n = 24) and TRF (n = 24) for six months. Blood was taken at baseline (month 0), 3 months and 6 months osf supplementation for determination of plasma malondialdehyde (MDA), protein carbonyl, total DNA damage, vitamin D concentration and vitamin E isomers. α-TF supplementation reduced plasma MDA and protein carbonyl in female subjects after 3 and 6 months. TRF supplementation reduced MDA levels in both males and females as early as 3 months while DNA damage was reduced in females only at 6 months. Supplementation with α-TF and TRF increased plasma vitamin D concentration in both males and females after 6 months, but vitamin D concentration in male subjects were significantly higher compared to female subjects in TRF group. Vitamin E isomer determination showed α-TF, α-tocotrienol and γ-tocotrienol were increased in both male and female subjects. In conclusion, TRF supplementation effects were different from α-TF in reducing oxidative stress markers and vitamin D levels with a more pronounced effect in female subjects.

Radioprotective Efficacy of Gamma-Tocotrienol in Nonhuman Primates.

The search for treatments to counter potentially lethal radiation-induced injury over the past several decades has led to the development of multiple classes of radiation countermeasures. However, to date only granulocyte colony-stimulating factor (G-CSF; filgrastim, Neupogen)and pegylated G-CSF (pegfilgrastim, Neulasta) have been approved by the United States Food and Drug Administration (FDA) for the treatment of hematopoietic acute radiation syndrome (ARS). Gamma-tocotrienol (GT3) has demonstrated strong radioprotective efficacy in the mouse model, indicating the need for further evaluation in a large animal model. In this study, we evaluated GT3 pharmacokinetics (PK) and efficacy at different doses of cobalt-60 gamma radiation (0.6 Gy/min) using the nonhuman primate (NHP) model. The PK results demonstrated increased area under the curve with increasing drug dose and half-life of GT3. GT3 treatment resulted in reduced group mean neutropenia by 3-5 days and thrombocytopenia by 1-5 days. At 5.8 and 6.5 Gy total-body irradiation, GT3 treatment completely prevented thrombocytopenia. The capability of GT3 to reduce severity and duration of neutropenia and thrombocytopenia was dose dependent; 75 mg/kg treatment was more effective than 37.5 mg/kg treatment after a 5.8 Gy dose. However, the higher GT3 dose (75 mg/kg) was associated with higher frequency of adverse skin effects (small abscess) at the injection site. GT3 treatment of irradiated NHPs caused no significant difference in animal survival at 60 days postirradiation, however, low mortality was observed in irradiated, vehicle-treated groups as well. The data from this pilot study further elucidate the role and pharmacokinetics of GT3 in hematopoietic recovery after irradiation in a NHP model, and demonstrate the potential of GT3 as a promising radioprotector.

Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits.

Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1ß, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply.

Graded hypoxia and blood oxidative stress during exercise recovery.

Altitude exposure and exercise elicit oxidative stress in blood; however, exercise recovery at 5000 m attenuates oxidative stress. The purpose was to determine the altitude threshold at which blood oxidative stress is blunted during exercise recovery. Twelve males 18-28 years performed four-cycle ergometry bouts (60 min, 70% VO2max, at 975 m). In a randomised counterbalanced crossover design, participants recovered 6 h at 0, 1667, 3333 and 5000 m in a normobaric hypoxia chamber (recovery altitudes were simulated by using a computerised system in an environmental chamber by lowering the partial pressure of oxygen to match that of the respective altitude). Oxygen saturation was monitored throughout exercise recovery. Blood samples obtained pre-, post-, 1 h post- and 5 h post-exercise were assayed for ferric-reducing antioxidant plasma, Trolox equivalent antioxidant capacity, uric acid, lipid hydroperoxides and protein carbonyls. Muscle biopsies obtained pre and 6 h were analysed by real-time polymerase chain reaction to quantify expression of hemeoxgenase 1, superoxide dismutase 2 and nuclear factor (euthyroid-derived 2)-like factor. Pulse oximetry data were similar during exercise, but decreased for the three highest recovery elevations (0 m = 0%, 1667 m = -3%; 3333 m = -7%; 5000 m = -17%). A time-dependent oxidative stress occurred following exercise for all variables, but the two highest recovery altitudes partially attenuated the lipid hydroperoxide response (0 m = +135%, 1667 m = +251%, 3333 m = +99%; 5000 m = +108%). Data may indicate an altitude threshold between 1667 and 3333 m, above which the oxidative stress response is blunted during exercise recovery.

Analysis of vitamin E metabolites including carboxychromanols and sulfated derivatives using LC/MS/MS.

Tocopherols and tocotrienols are metabolized via hydroxylation and oxidation of their hydrophobic side chain to generate 13'-hydroxychromanols (13'-OHs) and various carboxychromanols, which can be further metabolized by conjugation including sulfation. Recent studies indicate that long-chain carboxychromanols, especially 13'-carboxychromanol (13'-COOH), appear to be more bioactive than tocopherols in anti-inflammatory and anticancer actions. To understand the potential contribution of metabolites to vitamin E-mediated effects, an accurate assay is needed to evaluate bioavailability of these metabolites. Here we describe an LC/MS/MS assay for quantifying vitamin E metabolites using negative polarity ESI. This assay includes a reliable sample extraction procedure with efficacy of ≥ 89% and interday/intraday variation of 3-11% for major metabolites. To ensure accurate quantification, short-chain, long-chain, and sulfated carboxychromanols are included as external/internal standards. Using this assay, we observed that sulfated carboxychromanols are the primary metabolites in the plasma of rodents fed with γ-tocopherol or δ-tocopherol. Although plasma levels of 13'-COOHs and 13'-OHs are low, high concentrations of these compounds are found in feces. Our study demonstrates an LC/MS/MS assay for quantitation of sulfated and unconjugated vitamin E metabolites, and this assay will be useful for evaluating the role of these metabolites in vivo.

[Age-related changes in antioxidant parameters in healthy calves between the first day of life and the 18th month taking into consideration selected metabolic parameters]. / Altersabhängige Veränderungen antioxidativer Parameter bei gesunden Kälbern zwischen dem 1. Lebenstag und dem 18. Lebensmonat. Untersuchung unter Berücksichtigung ausgewählter Stoffwechselparameter.

OBJECTIVE: To follow the age-dependent development of anti-oxidative metabolic parameters in healthy cattle from birth until 18 months of age. MATERIAL AND METHODS: Blood samples from healthy female cattle were collected at days 1 and 7 post natum (p. n.) and during the 1st, 3rd, 6th, 9th, 12th and 18th month p. n. The antioxidant parameters superoxide dismutase (SOD), glutathione peroxidase (GPX) and Trolox equivalent antioxidative capacity (TEAC), haematocrit (Hct) and the metabolic parameters total protein, albumin, bilirubin, calcium, inorganic phosphate, iron, urea, cholesterol, ß-hydroxybutyrate, alkaline phosphatase, aspartate transaminase, glutamate dehydrogenase, creatine kinase and haptoglobin were determined. RESULTS: All three antioxidant parameters displayed a comparable time-course, with a maximum at 6 months p. n. With the exception of the 9th month p. n., significantly positive correlations were found constantly. GPX activity increased continuously from 50-80 U/ml Hct on day 1 p. n. to 100-190 U/ml Hct in the 6th month p. n. The significantly lowest activities were found on the 1st and 7th day p. n. SOD activity at the 1st (4500-5600 U/g haemoglobin [Hb]) and 7th day p. n. were significantly lower than in the 1st and 3rd month p. n. Activi- ties at 12 and 18 months displayed significantly lower values com- pared to the 1st, 3rd and 6th (5000-9100 U/g Hb) month p. n. The increase in the TEAC concentration from 220-290 µmol/l on day 1 to 260-340 µmol/l in the 6th month p. n. was non-significant. Thereafter, a significant decrease in the concentrations (p>0.05) was found. CONCLUSION: Parallel trends for SOD, GPX and TEAC found in this study indicate a fully functioning antioxidant defence system in the calf, which is well adjusted to and able to compensate the inevitable oxidative stress of birth, onset of respiration, haemoglobin remodelling, forestomach development and other physiological processes.

Oxidant-antioxidant balance during on-pump coronary artery bypass grafting.

BACKGROUND: The aim of this study was to evaluate the changes in perioperative oxidant-antioxidant balance in ONCABG. METHODS: Twenty-three patients were included in this study. Serum total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) values were assessed preoperatively, at 20 minutes after aortic clamping and at 30 minutes, 6 hours, and 48 hours after declamping (reperfusion). The patients were divided into 2 groups according to the median aortic cross clamping (XC) time: group 1 (XC time < 42 minutes) and group 2 (XC time ≥ 42 minutes). RESULTS: TOS and OSI values of whole patients at 30 minutes after reperfusion were higher than preoperative values (P = 0.045, P = 0.015), while perioperative TAS levels of the patients were similar to the preoperative levels (P = 0.173). XC time was correlated with TOS levels at 30 minutes after reperfusion (r = 0.43, P = 0.041). In group 2, TOS and OSI values at 30 minutes after reperfusion were higher than preoperative values (P = 0.023, P = 0.048), whereas a significant difference was not found in group 1 (P = 0.601, P = 0.327). CONCLUSIONS: Oxidative imbalance and increase in TOS at reperfusion in ONCABG may be associated with XC time.

Insights on antioxidant assays for biological samples based on the reduction of copper complexes-the importance of analytical conditions.

Total antioxidant capacity assays are recognized as instrumental to establish antioxidant status of biological samples, however the varying experimental conditions result in conclusions that may not be transposable to other settings. After selection of the complexing agent, reagent addition order, buffer type and concentration, copper reducing assays were adapted to a high-throughput scheme and validated using model biological antioxidant compounds of ascorbic acid, Trolox (a soluble analogue of vitamin E), uric acid and glutathione. A critical comparison was made based on real samples including NIST-909c human serum certified sample, and five study samples. The validated method provided linear range up to 100 µM Trolox, (limit of detection 2.3 µM; limit of quantification 7.7 µM) with recovery results above 85% and precision <5%. The validated developed method with an increased sensitivity is a sound choice for assessment of TAC in serum samples.

Acute hypoxia and exercise-induced blood oxidative stress.

Hypoxic exercise is characterized by workloads decrements. Because exercise and high altitude independently elicit redox perturbations, the study purpose was to examine hypoxic and normoxic steady-state exercise on blood oxidative stress. Active males (n = 11) completed graded cycle ergometry in normoxic (975 m) and hypoxic (3,000 m) simulated environments before programing subsequent matched intensity or workload steady-state trials. In a randomized counterbalanced crossover design, participants completed three 60-min exercise bouts to investigate the effects of hypoxia and exercise intensity on blood oxidative stress. Exercise conditions were paired as such; 60% normoxic VO(2)peak performed in a normoxic environment (normoxic intensity-normoxic environment, NI-NE), 60% hypoxic VO(2)peak performed in a normoxic environment (HI-NE), and 60% hypoxic VO(2)peak performed in a hypoxic environment (HI-HE). Blood plasma samples drawn pre (Pre), 0 (Post), 2 (2HR) and 4 (4HR) hr post exercise were analyzed for oxidative stress biomarkers including ferric reducing ability of plasma (FRAP), trolox equivalent antioxidant capacity (TEAC), lipid hydroperoxides (LOOH) and protein carbonyls (PCs). Repeated-measures ANOVA were performed, a priori significance of p ≤ .05. Oxygen saturation during the HI-HE trial was lower than NI-NE and HI-NE (p < .05). A Time × Trial interaction was present for LOOH (p = .013). In the HI-HE trial, LOOH were elevated for all time points post while PC (time; p = .001) decreased post exercise. As evidenced by the decrease in absolute workload during hypoxic VO(2)peak and LOOH increased during HI-HE versus normoxic exercise of equal absolute (HI-NE) and relative (NI-NE) intensities. Results suggest acute hypoxia elicits work decrements associated with post exercise oxidative stress.

Influence of single hemodialysis session on serum paraoxonase-1, arylesterase activity, total oxidant status and total antioxidant status.

AIM: Chronic kidney disease(CKD) and hemodialysis (HD) are associated with increased oxidative stress. Cardiovascular diseases (CVD) are the most important cause of mortality in these patients. Increased cardiovascular risk is associated with oxidative stress. The aim of this study was to evaluate whether the duration of single session hemodialysis may affect oxidative stress parameters on the patients with end-stage renal disease (ESRD). METHODS: Total oxidant status (TOS) and oxidative stress index (OSI) as oxidative markers and total antioxidant status (TAOS), paraoxonase1 (PON1) and arylesterase (ARES) as antioxidant markers were compared hemodialysis therapy before and after the treatment. RESULTS: TOS levels before hemodialysis were found as 4.4±2.4 µmol H2O2 Equiv/L, TAOS 2.1±0.3 µmol trolox Equiv./L, OSI 0.2±0.1%, PON1 levels 58.5±35.6 U/L and ARES levels 22±0.2 U/L while after the HD the respective values were 1.4±1.2 µmol H2O2 Equiv/L, 1.4±0.5 µmol trolox Equiv./L, 0.1±0.1%, 54.3±31.3 U/L, 21.8±0.1 U/L. A significant decreasing was observed in TOS TAOS OSI and ARES values before the HD compared to after the HD (P=0.0001, P=0.0001, P=0.0001, P=0.031, respectively). CONCLUSION: This study shows oxidant (TOS, OSI) and antioxidant (TAOS, ARES) markers were found to be significantly decrease after the HD compared to pre-hemodialysis. Although reverse is expected it is found that oxidants (indirectly ROS) did not increase and antioxidant reserve decreased in HD.

Impact of a customised dietary intervention on antioxidant status, dietary intakes and periodontal indices in patients with adult periodontitis.

BACKGROUND: Dietary modification may be important in the prevention and control of chronic adult periodontitis. The role of promoting an adequate consumption of fruits, vegetables and whole grains in chronic periodontitis has not been thoroughly investigated. The main aim of this dietary intervention study was to assess the influence of a customised dietary intervention (aiming to increase the consumption of fruits, vegetables and whole grains) on antioxidant status in adults with chronic periodontitis. METHODS: Fifty-one participants, aged 30-65 years, were recruited from a U.K. Dental Hospital and randomly allocated to an intervention or control group. Both groups received normal clinical treatment but customised dietary advice was delivered to the intervention group by a community nutrition assistant. Dietary intakes, anthropometric parameters and biochemical indices with respect to blood and saliva and periodontal indices were evaluated at baseline, as well as at 3 and 6 months post-dietary intervention. RESULTS: At 3 and 6 months post-intervention, the intervention group showed a significant (P < 0.05) increase in plasma total antioxidant capacity measured by Trolox equivalent antioxidant capacity assay compared to the control group. At 3 and 6 months after dietary intervention, the intervention group had significantly higher intakes of fruits and vegetables compared to the control group. The intake of whole grain was significantly higher in the intervention group than in the control group, 6 months post-intervention. No significant differences were observed with respect to periodontal indices between groups. CONCLUSIONS: It is suggested that dietary advice may help to improve dietary habits and, consequently, the antioxidant status of patients with chronic periodontitis. However, the impact of such intervention on periodontal indices needs further investigation.

Highly sensitive determination of new metabolite in rat plasma after oral administration of swertiamarin by liquid chromatography/time of flight mass spectrometry following picolinoyl derivatization.

The metabolism of swertiamarin (STM) in vivo was studied by LC/MS following picolinoyl derivatization. Incubation of erythrocentaurin (ECR), one of the main in vitro metabolites of STM by intestinal bacteria, with liver microsome indicated that STM may be metabolized to the final metabolite 3,4-dihydro-5-(hydroxymethyl) isochroman-1-one (HMIO) in vivo. After hydrolyzation with sulfatase, HMIO was successfully detected in rat plasma after oral administration of STM by LC/MS following picolinoyl derivatization. 4-Methoxyphenyl methanol was used as the internal standard to quantify HMIO in rat plasma. The full metabolic pathway of STM in rats is proposed. STM is first hydrolyzed by bacterial ß-glucusidase to give aglycone, which is readily converted to ECR and nitrogen-containing metabolite. ECR is further reduced to HMIO by both liver and intestinal bacteria and HMIO is finally converted to the new sulfate conjugate metabolite. The monoterpene compound STM was found to be metabolized to dihydroisocoumarin and alkaloid compounds in vivo, which may be responsible for the pharmacological effect of STM. The results may shed light on clinical efficacy of STM and the new analytical method developed may assist in studies of the metabolism of other natural iridoids and secoiridoids in vivo.

High-fat feeding, but not strenuous exercise, increases blood oxidative stress in trained men.

Two prevalent origins of oxidative stress in Western society are the ingestion of high-fat meals and the performance of strenuous exercise. The purpose of this investigation was to compare the magnitude of increase in blood oxidative stress following acute feeding and acute exercise. Twelve exercise-trained men consumed a high-fat meal or performed 1 of 3 exercise bouts (steady-state aerobic; high-intensity, moderate-duration interval sprints; maximal intensity, short-duration interval sprints) in a random order, crossover design. Blood was collected before and at times following feeding and exercise. Samples were analyzed for trigylcerides, malondialdehyde (MDA), hydrogen peroxide (H(2)O(2)), advanced oxidation protein products (AOPP), nitrate/nitrite (NOx), trolox-equivalent antioxidant capacity (TEAC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). A significant condition effect was noted for MDA (p = 0.01), H(2)O(2) (p < 0.0001), and AOPP (p = 0.0006), with values highest for the meal condition. An increase of 88%, 247%, and 96% was noted from pre- to post-feeding for MDA, H(2)O(2), and AOPP, respectively. A condition effect was also noted for TEAC (p = 0.04) and CAT (p = 0.05), with values lowest for the meal condition (TEAC) and the meal and aerobic exercise condition (CAT). NOx, SOD, and GPx were relatively unaffected by feeding and exercise, while MDA, H(2)O(2), and AOPP experienced little change from pre- to postexercise (p > 0.05). These results illustrate that the magnitude of blood oxidative stress following a high-fat meal is significantly greater than that elicited by either aerobic or anaerobic exercise in a sample of exercise-trained men.

Classification and prediction of clinical diagnosis of Alzheimer's disease based on MRI and plasma measures of α-/γ-tocotrienols and γ-tocopherol.

BACKGROUND: The aim of this study was to evaluate the accuracy of combined structural magnetic resonance imaging (MRI) measures and plasma levels of vitamin E forms, including all eight natural vitamin E congeners (four tocopherols and four tocotrienols) and markers of vitamin E oxidative/nitrosative damage, in differentiating individuals with Alzheimer's disease (AD) and mild cognitive impairment (MCI) from cognitively intact control (CTL) subjects. METHODS: Overall, 81 patients with AD, 86 with MCI and 86 CTL individuals were enrolled from the longitudinal multicentre AddNeuroMed study. MRI and plasma vitamin E data were acquired at baseline. MRI scans were analysed using Freesurfer, an automated segmentation scheme which generates regional volume and cortical thickness measures. Orthogonal partial least squares to latent structures (OPLS), a multivariate data analysis technique, was used to analyse MRI and vitamin E measures in relation to AD and MCI diagnosis. RESULTS: The joint evaluation of MRI and plasma vitamin E measures enhanced the accuracy of differentiating individuals with AD and MCI from CTL subjects: 98.2% (sensitivity 98.8%, specificity 97.7%) for AD versus CTL, and 90.7% (sensitivity 91.8%, specificity 89.5%) for MCI versus CTL. This combination of measures also identified 85% of individuals with MCI who converted to clinical AD at follow-up after 1 year. CONCLUSIONS: Plasma levels of tocopherols and tocotrienols together with automated MRI measures can help to differentiate AD and MCI patients from CTL subjects, and to prospectively predict MCI conversion into AD. Our results suggest the potential role of nutritional biomarkers detected in plasma-tocopherols and tocotrienols-as indirect indicators of AD pathology, and the utility of a multimodality approach.