Proteome changes in a human retinal pigment epithelial cell line during oxidative stress and following antioxidant treatment.

Age related macular degeneration (AMD) is the most common cause of blindness in the elderly. Oxidative stress contributes to retinal pigment epithelium (RPE) dysfunction and cell death thereby leading to AMD. Using improved RPE cell model systems, such as human telomerase transcriptase-overexpressing (hTERT) RPE cells (hTERT-RPE), pathophysiological changes in RPE during oxidative stress can be better understood. Using this model system, we identified changes in the expression of proteins involved in the cellular antioxidant responses after induction of oxidative stress. Some antioxidants such as vitamin E (tocopherols and tocotrienols) are powerful antioxidants that can reduce oxidative damage in cells. Alpha-tocopherol (α-Toc or αT) and gamma-tocopherol (γ-Toc or γT) are well-studied tocopherols, but signaling mechanisms underlying their respective cytoprotective properties may be distinct. Here, we determined what effect oxidative stress, induced by extracellularly applied tBHP in the presence and absence of αT and/or γT, has on the expression of antioxidant proteins and related signaling networks. Using proteomics approaches, we identified differential protein expression in cellular antioxidant response pathways during oxidative stress and after tocopherol treatment. We identified three groups of proteins based on biochemical function: glutathione metabolism/transfer, peroxidases and redox-sensitive proteins involved in cytoprotective signaling. We found that oxidative stress and tocopherol treatment resulted in unique changes in these three groups of antioxidant proteins indicate that αT and γT independently and by themselves can induce the expression of antioxidant proteins in RPE cells. These results provide novel rationales for potential therapeutic strategies to protect RPE cells from oxidative stress.

Genome-wide scan for oil quality reveals a coregulation mechanism of tocopherols and fatty acids in soybean seeds.

Tocopherols (vitamin E) play essential roles in human health because of their antioxidant activity, and plant-derived oils are the richest sources of tocopherols in the human diet. Although soybean (Glycine max) is one of the main sources of plant-derived oil and tocopherol in the world, the relationship between tocopherol and oil in soybean seeds remains unclear. Here, we focus on dissecting tocopherol metabolism with the long-term goal of increasing α-tocopherol content and soybean oil quality. We first collected tocopherol and fatty acid profiles in a soybean population (>800 soybean accessions) and found that tocopherol content increased during soybean domestication. A strong positive correlation between tocopherol and oil content was also detected. Five tocopherol pathway-related loci were identified using a metabolite genome-wide association study strategy. Genetic variations in three tocopherol pathway genes were responsible for total tocopherol content and composition in the soybean population through effects on enzyme activity, mainly caused by non-conserved amino acid substitution or changes in gene transcription level. Moreover, the fatty acid regulatory transcription factor GmZF351 directly activated tocopherol pathway gene expression, increasing both fatty acid and tocopherol contents in soybean seeds. Our study reveals the functional differentiation of tocopherol pathway genes in soybean populations and provides a framework for development of new soybean varieties with high α-tocopherol content and oil quality in seeds.

Phytocompounds From Edible Oil Seeds Target Hub Genes To Control Breast Cancer.

Breast cancer is one of the most commonly diagnosed cancers in woman which accounts for more than 1 in 10 new cancers in the entire world. The recently found four new potential hub genes that show a strong expression in breast cancer are CCNA2, CCNB1, MAD2L1, and RAD51. Nowadays, food habits and lifestyle of an individual are one of the factors for causing cancers. Consumption of seeds on a regular basis is the key factor for leading a good health. Sesame seeds and Sunflower seeds are few examples of cancer fighting seeds. Sesame (Sesamum indicum) is one of the earliest oil seed plant with various phytocompounds present which include lignans, tocopherols, phenolics, polyunsaturated fatty acids, and phytosterols. Sunflower (Helianthus annuus L.) is primarily harvested as an oil seed plant with various phytocompounds present which include flavonoids, phenolic acids, tocopherols, and vitamin B3. These are the few seeds that help women to prevent and also to fight against Breast cancer with its potential anti-cancer activity. The main objective of the current study is to identify the potential phytocompounds present in the cancer fighting seeds using molecular docking and dynamic simulation approach which can further help pharmaceuticals industries in producing targeted drugs against breast cancer hub genes as well as food industries in producing products combining the potential phytocompounds present in the seeds.

Comprehensive analysis of the GALACTINOL SYNTHASE (GolS) gene family in citrus and the function of CsGolS6 in stress tolerance.

Galactinol synthase (GolS) catalyzes the first and rate-limiting step in the synthesis of raffinose family of oligosaccharides (RFOs), which serve as storage and transport sugars, signal transducers, compatible solutes and antioxidants in higher plants. The present work aimed to assess the potential functions of citrus GolS in mechanisms of stress response and tolerance. By homology searches, eight GolS genes were found in the genomes of Citrus sinensis and C. clementina. Phylogenetic analysis showed that there is a GolS ortholog in C. clementina for each C. sinensis GolS, which have evolved differently from those of Arabidopsis thaliana. Transcriptional analysis indicated that most C. sinensis GolS (CsGolS) genes show a low-level tissue-specific and stress-inducible expression in response to drought and salt stress treatments, as well as to 'Candidatus Liberibacter asiaticus' infection. CsGolS6 overexpression resulted in improved tobacco tolerance to drought and salt stresses, contributing to an increased mesophyll cell expansion, photosynthesis and plant growth. Primary metabolite profiling revealed no significant changes in endogenous galactinol, but different extents of reduction of raffinose in the transgenic plants. On the other hand, a significant increase in the levels of metabolites with antioxidant properties, such as ascorbate, dehydroascorbate, alfa-tocopherol and spermidine, was observed in the transgenic plants. These results bring evidence that CsGolS6 is a potential candidate for improving stress tolerance in citrus and other plants.

Tocopherol Enhances the Antioxidant Defense System and Histomorphometric Parameters in The Gastrointestinal Tract of Rats Treated with Sodium Arsenite.

Arsenic compromises the gastrointestinal integrity and function via the body's anti-oxidative system breakdown.  Hence, this study aimed to investigate the effects of tocopherol on redox imbalance and histoarchitectural alterations in rats' gastrointestinal tract exposed to sodium arsenite. Sodium arsenite and graded doses of tocopherol were administered orally into experimental rats assigned to different groups for four weeks concurrently. Redox status assay was done in homogenized samples by spectrophotometry. Parietal cell mass and mucous cell density (stomach), villus height and crypt depth (ileum), goblet cells count, and crypt depth (colon) were evaluated by histomorphometry. Inflammatory cells infiltration was also assessed using a semi-quantitative procedure. Sodium arsenite caused a significant increase in Malondialdehyde and Myeloperoxidase but, decreased Superoxide dismutase, Catalase, Nitric oxide, Glutathione peroxidase, Glutathione, and Glutathione-S-Transferase. Tocopherol treatment reversed the changes (p<0.05) though not largely dose-dependent. Furthermore, tocopherol annulled sodium arsenite-induced increase in parietal cell mass and decrease in mucous cell density in the stomach, decrease in villus height and villus height/crypt depth ratio in the ileum, and decrease in goblets cells and increase in crypt depth in the colon. Moreover, activated inflammatory cell infiltration by sodium arsenite was mitigated by tocopherol. Sodium arsenite provokes not only marked inflammatory cellular infiltration but a focal loss of glands, hyperplasia of crypts, atrophic villi, and hypertrophy of Peyer's patches in the intestines, which are all lessened with tocopherol treatment.  These findings underscore the anti-oxidative properties of tocopherol as a potent dietary factor against sodium arsenite toxicity in the gastrointestinal tract. Keywords: Tocopherol, arsenic, stomach, ileum, colon.

Combining GWAS and TWAS to identify candidate causal genes for tocochromanol levels in maize grain.

Tocochromanols (tocopherols and tocotrienols, collectively vitamin E) are lipid-soluble antioxidants important for both plant fitness and human health. The main dietary sources of vitamin E are seed oils that often accumulate high levels of tocopherol isoforms with lower vitamin E activity. The tocochromanol biosynthetic pathway is conserved across plant species but an integrated view of the genes and mechanisms underlying natural variation of tocochromanol levels in seed of most cereal crops remains limited. To address this issue, we utilized the high mapping resolution of the maize Ames panel of ∼1,500 inbred lines scored with 12.2 million single-nucleotide polymorphisms to generate metabolomic (mature grain tocochromanols) and transcriptomic (developing grain) data sets for genetic mapping. By combining results from genome- and transcriptome-wide association studies, we identified a total of 13 candidate causal gene loci, including 5 that had not been previously associated with maize grain tocochromanols: 4 biosynthetic genes (arodeH2 paralog, dxs1, vte5, and vte7) and a plastid S-adenosyl methionine transporter (samt1). Expression quantitative trait locus (eQTL) mapping of these 13 gene loci revealed that they are predominantly regulated by cis-eQTL. Through a joint statistical analysis, we implicated cis-acting variants as responsible for colocalized eQTL and GWAS association signals. Our multiomics approach provided increased statistical power and mapping resolution to enable a detailed characterization of the genetic and regulatory architecture underlying tocochromanol accumulation in maize grain and provided insights for ongoing biofortification efforts to breed and/or engineer vitamin E and antioxidant levels in maize and other cereals.

Tocopherol contents and antioxidant activity in grape pomace after fermentation and alcohol distillation.

The wine industry in Georgia produces vast amounts of grape pomace that is currently mostly wasted, while only a minor amount is used for distilling alcohol. The study was carried out on the grape pomace from the three most widely used grapevine sorts (Vitis vinifera var. Rkatsiteli, V. vinifera var. Saperavi, V. labrusca var. Isabella)  in Georgia, and quantities of tocopherols and antioxidants were evaluated. The antioxidant activity was assessed by diphenyl-picrylhydrazyl (DPPH) and measurement of visible light absorption at 515 nm, and tocopherol was measured by absorption at 470 nm via a spectrophotometer. The results indicated that the grape pomace contains considerable tocopherols and antioxidant activity. However, the antioxidant activity had slightly been decreased. These results suggest that grape pomace can be an economically attractive resource for the pharmaceutical and food industries. Utilization of grape pomace for producing pharmaceutical and cosmetic goods with tocopherol and antioxidants can solve two problems: it can recycle waste and develop new profitable businesses in biotechnology.

Dietary supplementations of methionine improve growth performances, innate immunity, digestive enzymes, and antioxidant activities of rohu (Labeo rohita).

The dietary composition of fish constitutes numerous immune and growth-promoting substance; during the current study, methionine was amended in the diet of Labeo rohita (L. rohita), in order to appraise the diverse modulatory effects of methionine supplementation. Fish were grouped into three on the basis of methionine as methionine supplemented group 1 (MSG1), methionine supplemented group 2 (MSG2), and CTRL (control group). We assessed the effects of methionine at the end. Captivating results were obtained from the methionine supplementing groups. The results depict significantly high (p < 0.05) innate immunity parameters, including myeloperoxidase, IgG concentrations, lysozyme, respiratory burst, and total bacteriolytic activity of complement in MSG2. Furthermore, ameliorate growth performances were also noticed such as high weight gain, FCE%, and body length in MSG2, respectively. We also measured high level of antioxidant digestive enzymes, gut length, and survival rate in MSG2 compared to the rest of the groups. The results were further validated by measuring the stress parameters, such as aspartate aminotransferase (AST), glucose, and hematocrit (HCT%), and the concentration remains low in MSG2. Lastly, after 90 days, fish were challenged with Aeromonas hydrophila, the highest survival was observed in the MSG2 and MSG1 compared to CTRL. These results ultimately give the baseline to the credible effects of methionine on L. rohita.

Slow-binding inhibitors of acetylcholinesterase of medical interest.

Certain ligands slowly bind to acetylcholinesterase. As a result, there is a slow establishment of enzyme-inhibitor equilibrium characterized by a slow onset of inhibition prior reaching steady state. Three mechanisms account for slow-binding inhibition: a) slow binding rate constant kon, b) slow ligand induced-fit following a fast binding step, c) slow conformational selection of an enzyme form. The slow equilibrium may be followed by a chemical step. This later that can be irreversible has been observed with certain alkylating agents and substrate transition state analogs. Slow-binding inhibitors present long residence times on target. This results in prolonged pharmacological or toxicological action. Through several well-known molecules (e.g. huperzine) and new examples (tocopherol, trifluoroacetophenone and a 6-methyluracil alkylammonium derivative), we show that slow-binding inhibitors of acetylcholinesterase are promising drugs for treatment of neurological diseases such as Alzheimer disease and myasthenia gravis. Moreover, they may be of interest for neuroprotection (prophylaxis) against organophosphorus poisoning. This article is part of the special issue entitled 'Acetylcholinesterase Inhibitors: From Bench to Bedside to Battlefield'.

Carotenoid, Tocopherol, and Phenolic Compound Content and Composition in Cover Crops Used as Forage.

Secondary compounds of grassland and forage plant species such as vitamins or phenolic compounds are involved in different health-promoting effects in animals. However, information on their concentration and composition in forage plant species remains scarce. The objective of this study was to characterize the composition of secondary compounds of seven grazed cover crop plant species harvested at two stages of growth. Carotenoids and tocopherols were characterized and quantified using ultraperformance liquid chromatography with a photodiode array, and soluble phenolic compounds were characterized using high-performance liquid chromatography with diode-array detection. All species were rich in carotenoids, especially at the vegetative stage, even if the concentrations varied between plant species. Variations in tocopherol concentrations and phenolic composition were more important between plant species than between stages within species. Among the plant species tested, sainfoin (Onobrychis viciifolia Scop) contained the most secondary metabolites.

Endoplasmic reticulum-targeted glutathione and pH dual responsive vitamin lipid nanovesicles for tocopheryl DM1 delivery and cancer therapy.

The major drawbacks of the cytotoxin like DM1 are the off-target effects. Here, the targeting nanovesicles were developed by synthesizing tocopherol-SS-DM1 and conjugating a pH low insertion peptide (pHLIP) to PEGylated phospholipids, in which tocopherol-SS-DM1 improves the drug loading and is glutathione responsive in the cytoplasm, meanwhile, the pH insertion peptide targets the acidic microenvironment of cancer cells. Besides, these nanovesicles can accumulate at the endoplasmic reticulum and show increased cancer therapeutic effects both in vitro and in vivo. These targeting nanovesicles provide a novel formulation for subcellular organelle targeting, a platform for precisely delivery of cytotoxic DM1 to cancer cells, and an alternative strategy for antibody-drug conjugates (ADCs).

The inhibitor-evoked shortage of tocopherol and plastoquinol is compensated by other antioxidant mechanisms in Chlamydomonas reinhardtii exposed to toxic concentrations of cadmium and chromium ions.

One of the major mechanisms of heavy metal toxicity is the induction of oxidative stress. Redox-active heavy metals, like chromium, can induce it directly, whereas redox-inactive metals, like cadmium, play an indirect role in the generation of reactive oxygen species (ROS). Living organisms defend themselves against oxidative stress taking advantage of low-molecular-weight antioxidants and ROS-detoxifying enzymes. Tocopherols and plastoquinol are important plastid prenyllipid antioxidants, playing a role during acclimation of Chlamydomonas reinhardtii to heavy metal-induced stress. However, partial inhibition of synthesis of these prenyllipids by pyrazolate did not decrease the tolerance of C. reinhardtii to Cr- and Cd-induced stress, suggesting redundancy between antioxidant mechanisms. To verify this hypothesis we have performed comparative analyses of growth, photosynthetic pigments, low-molecular-weight antioxidants (tocopherols, plastoquinol, plastochromanol, ascorbate, soluble thiols, proline), activities of the ascorbate peroxidase (APX), catalase and superoxide dismutase (SOD) and cumulative superoxide production in C. reinhardtii exposed to Cd2+ and Cr2O72- ions in the presence or absence of pyrazolate. The decreased α-tocopherol and plastoquinol content resulted in the increase in superoxide generation and APX activity in pyrazolate-treated algae. The application of heavy metal ions and pyrazolate had a pronounced impact on Asc and total thiol content, as well as SOD and APX activities (the latter only in Cd-exposed cultures), when compared with algae grown in the presence of heavy metal ions or pyrazolate alone. The superoxide production in cultures exposed to heavy metal ions and pyrazolate decreased when compared to the cultures exposed to either heavy metal ions or an inhibitor alone.

Antioxidant Phytochemicals in Pulses and their Relation to Human Health: A Review.

Pulses are a staple food cultivated since ancient times, which play an important role in the human diet. From a nutritional point of view, pulses are very interesting foods as they are rich in proteins, carbohydrates and dietary fibre. Dietary antioxidants are a complex mixture of hydrophilic and lipophilic compounds usually present in foods of plant origin, including pulses. In the present study, the phytochemical composition of selected pulses (common beans, fava beans, lentils, chickpeas, peas and lupins) has been reviewed in terms of their content of antioxidant compounds. The content of hydrosoluble antioxidants (organic acids, phenolic compounds), liposoluble antioxidants (tocopherols, carotenoids) and other compounds which exert antioxidant properties, such as dietary fibre and minerals (zinc, selenium), has been studied, reporting that pulses are an interesting source of these compounds, which have important health benefits, including a preventing role in cardiovascular diseases, anticarcinogenic or neuroprotective properties. It is important to take into account that pulses are not usually consumed raw, but they must be processed before consumption in order to improve their nutritional quality and their palatability, therefore, the effect of different technological and heat treatments (germination, cooking, boiling, extrusion) on the antioxidant compounds present in pulses has been also reviewed. In this regard, it has been observed that as a consequence of processing, the content of phytochemicals with antioxidant properties is usually decreased, but processed pulses maintain relevant amounts of these compounds, preserving their beneficial health effect.

The antioxidant vitamin E as a membrane raft modulator: Tocopherols do not abolish lipid domains.

The antioxidant vitamin E is a commonly used vitamin supplement. Although the multi-billion dollar vitamin and nutritional supplement industry encourages the use of vitamin E, there is very little evidence supporting its actual health benefits. Moreover, vitamin E is now marketed as a lipid raft destabilizing anti-cancer agent, in addition to its antioxidant behaviour. Here, we studied the influence of vitamin E and some of its vitamers on membrane raft stability using phase separating unilamellar lipid vesicles in conjunction with small-angle scattering techniques and fluorescence microscopy. We find that lipid phase behaviour remains unperturbed well beyond physiological concentrations of vitamin E (up to a mole fraction of 0.10). Our results are consistent with a proposed line active role of vitamin E at the domain boundary. We discuss the implications of these findings as they pertain to lipid raft modification in native membranes, and propose a new hypothesis for the antioxidant mechanism of vitamin E.

Changes in Antioxidant Activity, Profile, and Content of Polyphenols and Tocopherols in Common Hazel Seed (Corylus avellana L.) Depending on Variety and Harvest Date.

The aim of the study was to evaluate the influence of variety and the date of harvest of hazelnut seeds on their antioxidant potential and the profile and content of polyphenols and tocopherols. The research material included the hazelnut seeds of six varieties, harvested from July to September at equal 30-day intervals. Hazelnuts were analyzed for total fat content and antioxidant properties, whereby UPLC-PDA-ESI-MS analysis was used to determine the profile and content of polyphenols, and the HPLC method to determine the content of tocopherols. It was found that the content of fat and tocopherols in nuts increased with the ripening of the nuts. The highest fat content was found in walnut seeds of the Katalonski variety (September) and tocopherols in walnut seeds of the Olbrzym z Halle variety (177.67 mg/kg d.m.). In turn, antioxidant properties and total polyphenols content decreased with the later harvest date. The strongest antioxidant potential was found in the case of Cosford nuts harvested in July (66.93 mmol TE/100 g d.m.). These nuts were also characterized by the highest total polyphenol content (1704.9 mg/100 g d.m.). UPLC-MS analysis allowed the identification of 15 polyphenolic compounds such as phenolic acids, catechins and ellagic acid hexoside in nut seeds.

Influence of minor components on lipid bioaccessibility and oxidation during in vitro digestion of soybean oil.

BACKGROUND: Minor components of edible oils could influence their evolution during in vitro digestion. This might affect the bioaccessibility of lipid nutrients and the safety of the ingested food. Bearing this in mind, the evolution of virgin and refined soybean oils, which are very similar in acyl group composition, has been studied throughout in vitro digestion using 1 H nuclear magnetic resonance (NMR) and solid-phase microextraction-gas chromatography /mass spectrometry, focusing on lipolysis and oxidation reactions. The fate of γ-tocopherol, the main antioxidant present in soybean oil, has also been analyzed with 1 H NMR. RESULTS: There were no noticeable differences in lipolysis between the two oils that were studied. The extent of oxidation during digestion, which was very low in both cases, was slightly higher in the virgin type, which showed lower tocopherols and squalene concentrations than the refined one, together with a considerable abundance of free fatty acids. This can be deduced both from the appearance after digestion of conjugated hydroperoxy- and hydroxy-dienes only in the virgin oil, and from its higher levels of volatile aldehydes and 2-pentyl-furan. Under in vitro digestion conditions, the formation of epoxides seemed to be favored over other oxidation products. Finally, although some soybean oil essential nutrients like polyunsaturated fatty acids exhibited no significant degradation after digestion, γ-tocopherol concentration diminished during this process, especially in the virgin oil. CONCLUSION: Although the minor component composition of the soybean oils did not affect lipolysis during in vitro digestion, it influenced the extent of their oxidation and γ-tocopherol bioaccessibility. © 2019 Society of Chemical Industry.

Monitoring of minor compounds in corn oil oxidation by direct immersion-solid phase microextraction-gas chromatography/mass spectrometry. New oil oxidation markers.

The aim of this study is to shed light on the evolution of the minor compounds in the corn oil oxidation process, through the information provided by direct immersion-microextraction in solid phase followed by gas chromatography/mass spectrometry (DI-SPME-GC/MS). This methodology enables one, in a single run, to establish the identity and abundance both of original oil minor components, some with antioxidant capacity, and of other compounds coming from both main and minor oil components oxidation. For the first time, some of the compounds formed from oil minor components degradation are proposed as new markers of oil incipient oxidation. Although the study refers to corn oil, the methodology can be applied to any other edible oil and constitutes a new approach to characterizing the oxidation state of edible oils.

Quantitative Analysis of the Accumulation of Marine-derived Tocopherol in the Tissue of Mice Fed with Salmon Roe Oil Using HPLC-fluorescence.

In this study, we measured the quantity of marine-derived tocopherol (MDT), a monounsaturated vitamin E (VE), stored in the body tissue of mice fed with a diet containing a VE-rich fraction extracted from salmon roe. We first prepared the calibration curves for the MDT concentration using an HPLC-fluorescence system. Ranging from 0.016 to 50 µg/mL, the slope was expressed as first-order equations, with R2 values = 0.99. The mice were fed with an AIN-93 based diet containing MDT in doses of 21.4 mg/kg for 4 weeks, and the storage in the heart, lung, liver, stomach, small intestine, large intestine, kidney, pancreas, spleen, testis, skeletal muscle, visceral white adipose tissue (WAT), subcutaneous WAT and brain was quantified. MDT was widely distributed in tissues throughout the whole body, with higher accumulations observed in the adipose tissue, liver and kidney. These results demonstrate means to estimating the MDT concentration in natural products and in the bodies of animals and contribute to the understanding of the physiological functions of MDT in relation to human health.

The effects of feeding mixed tocopherol oil on whole-blood respiratory burst and neutrophil immunometabolic-related gene expression in lactating dairy cows.

The 4 major tocopherol isoforms differ in their biochemical reactivity and cellular effects due to basic chemical structural differences. Alpha-tocopherol has been well studied regarding effects on bovine polymorphonuclear leukocyte (PMN) function and its involvement in respiratory burst. However, no studies to date have identified the effects of supplementing a mixed tocopherol oil (Tmix) particularly enriched in non-α tocopherol isoforms (i.e., γ- and δ-isoforms) on fundamental immunometabolic changes in dairy cows. Therefore, the objectives of this study were to determine whether short-term feeding of vegetable oil-derived Tmix alters specific biomarkers of metabolism, whole-blood leukocyte populations, respiratory burst, immunometabolic-related gene expression of PMN, or gene expression of isolated PMN when challenged with lipopolysaccharides (LPS). Clinically healthy multiparous lactating Holstein cows (n = 12; 179 ± 17 d in milk, 40.65 ± 3.68 kg of milk yield) were fed Tmix (620 g/d) for 7 consecutive days. Jugular blood (EDTA anticoagulant) was collected from all cows on d 0 before treatment initiation and again on d 7 after Tmix feeding. Total stimulated respiratory burst activity (RBA) and leukocyte populations were assessed in whole blood, and tocopherol isoform concentrations, metabolites, and hormones were measured in plasma. For gene expression analysis, isolated PMN from cows before and after Tmix feeding were incubated with LPS at a final concentration of either 0.0 or 1.5 µg/mL. Feeding of Tmix for 7 d increased the concentrations of α- and γ-tocopherol. The Tmix did not alter plasma insulin but decreased cholesterol. The Tmix did not alter whole-blood RBA or the leukocyte populations. The LPS challenge increased the expression of proinflammatory genes TNFA and IL6. However, Tmix treatment did not alter the patterns of LPS-affected expression of genes (e.g., TNFA, ITGB2, PPARA, and RXRA) associated with the immune or metabolic response. In conclusion, short-term feeding of Tmix may have no negative effect on animal health as Tmix increased α- and γ-tocopherol concentrations in blood and did not impair whole-blood RBA or alter leukocyte populations. The data provide further support that the α- and γ-tocopherol isoforms do not interfere with normal immune or metabolic function.

Markers of oxidative damage to lipids, nucleic acids and proteins and antioxidant enzymes activities in Alzheimer's disease brain: A meta-analysis in human pathological specimens.

Oxidative stress and decreased cellular responsiveness to oxidative stress are thought to influence brain aging and Alzheimer's disease, but the specific patterns of oxidative damage and the underlying mechanism leading to this damage are not definitively known. The objective of this study was to define the pattern of changes in oxidative-stress related markers by brain region in human Alzheimer's disease and mild cognitive impairment brain tissue. Observational case-control studies were identified from systematic queries of PubMed, ISI Web of Science and Scopus databases and studies were evaluated with appropriate quality measures. The data was used to construct a region-by-region meta-analysis of malondialdehyde, 4-hydroxynonenal, protein carbonylation, 8-hydroxyguanine levels and superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase activities. We also evaluated ascorbic acid, tocopherol, uric acid and glutathione levels. The analysis was complicated in several cases by publication bias and/or outlier data. We found that malondialdehyde levels were slightly increased in the temporal and occipital lobes and hippocampus, but this analysis was significantly impacted by publication bias. 4-hydroxynonenal levels were unchanged in every brain region. There was no change in 8-hydroxyguanine level in any brain region and protein carbonylation levels were unchanged except for a slight increase in the occipital lobe. Superoxide dismutase, glutathione peroxidase and reductase and catalase activities were not decreased in any brain region. There was limited data reporting non-enzymatic antioxidant levels in Alzheimer's disease brain, although glutathione and tocopherol levels appear to be unchanged. Minimal quantitative data is available from brain tissue from patients with mild cognitive impairment. While there is modest evidence supporting minor regional changes in markers of oxidative damage, this analysis fails to identify a consistent pattern of pro-oxidative changes and accumulation of oxidative damage in bulk tissue analysis in the setting of Alzheimer's disease, as has been widely reported.