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Molecules (Basel, Switzerland) Apr 2023Microglia, the resident macrophage-like population in the central nervous system, play a crucial role in the pathogenesis of many neurodegenerative disorders by...
Microglia, the resident macrophage-like population in the central nervous system, play a crucial role in the pathogenesis of many neurodegenerative disorders by triggering an inflammatory response that leads to neuronal death. Neuroprotective compounds to treat or prevent neurodegenerative diseases are a new field of study in modern medicine. Microglia are activated in response to inflammatory stimuli. The pathogenesis of various neurodegenerative diseases is closely related to the constant activation of microglia due to their fundamental role as a mediator of inflammation in the brain environment. α-Tocopherol, also known as vitamin E, is reported to possess potent neuroprotective effects. The goal of this study was to investigate the biological effects of vitamin E on BV2 microglial cells, as a possible neuroprotective and anti-inflammatory agent, following stimulation with lipopolysaccharide (LPS). The results showed that the pre-incubation of microglia with α-tocopherol can guarantee neuroprotective effects during microglial activation induced by LPS. α-Tocopherol preserved the branched morphology typical of microglia in a physiological state. It also reduced the migratory capacity; the production of pro-inflammatory and anti-inflammatory cytokines such as TNF-α and IL-10; and the activation of receptors such as TRL4 and CD40, which modulate the PI3K-Akt signaling pathway. The results of this study require further insights and research, but they present new scenarios for the application of vitamin E as an antioxidant for the purpose of greater neuroprotection in vivo for the prevention of possible neurodegenerative diseases.
Topics: Humans; Lipopolysaccharides; Microglia; alpha-Tocopherol; Neuroprotective Agents; Phosphatidylinositol 3-Kinases; Macrophages; Anti-Inflammatory Agents; Vitamin E; Neurodegenerative Diseases; Nitric Oxide; NF-kappa B
PubMed: 37110573
DOI: 10.3390/molecules28083340 -
Current Opinion in Plant Biology Aug 2023Among the eight forms of vitamin E, only tocopherols are essential compounds that are distributed throughout the entire plant kingdom, with α-tocopherol being the most... (Review)
Review
Among the eight forms of vitamin E, only tocopherols are essential compounds that are distributed throughout the entire plant kingdom, with α-tocopherol being the most predominant form in photosynthetic tissues. At the cellular level, α-tocopherol is of special relevance inside the chloroplast, where it eliminates singlet oxygen and modulates lipid peroxidation. This is of utmost relevance since tocopherols are the only antioxidants that counteract lipid peroxidation. Moreover, at the whole-plant level, α-tocopherol appears to modulate several physiological processes from germination to senescence. The antioxidant role of α-tocopherol at the cellular level can have profound effects at the whole-plant level, including the modulation of physiological processes that are apparently not related to redox processes and could be considered non-antioxidant functions. Here, we discuss whether non-antioxidant functions of α-tocopherol at the whole-plant level are mediated by its antioxidant role in chloroplasts and the regulation of redox processes at the cellular level.
Topics: Antioxidants; alpha-Tocopherol; Vitamin E; Tocopherols; Chloroplasts
PubMed: 37311290
DOI: 10.1016/j.pbi.2023.102400 -
Molecules (Basel, Switzerland) Jan 2023Atopic dermatitis is a T-cell mediated inflammatory skin disease with detected elevated levels of histamine in skin or plasma. In this study, the effects of histamine in...
Atopic dermatitis is a T-cell mediated inflammatory skin disease with detected elevated levels of histamine in skin or plasma. In this study, the effects of histamine in a T2 cytokine environment on human keratinocytes and three-dimensional skin models were investigated. These models were used to explore the anti-inflammatory properties of the α-tocopherol-derived long-chain metabolite α-13'-carboxychromanol (α-13'-COOH). Histamine and T2 cytokine-induced proliferation of keratinocytes was studied using a scratch assay. The inflammatory marker interleukin-8 was significantly increased in healthy and T2 cytokine-stimulated keratinocytes and skin models after histamine treatment. The incubation of full-thickness skin models with T2 cytokines and histamine resulted in morphological changes in the epidermal layer, interpreted as hyperkeratosis. α-13'-COOH significantly decreased interleukin-8 in these disease-associated skin models. Histological staining of filaggrin showed skin-strengthening effects following α-13'-COOH treatment, without changes in mRNA expression. Cytokeratin 10 mRNA expression tended to be increased in response to α-13'-COOH. Anti-allergic properties of α-13'-COOH were studied by pre-incubation of human leukocytes with α-13'-COOH. This resulted in reduced sulfido-leukotriene synthesis. The hyperproliferation effect of histamine in atopic dermatitis skin models may be of further interest to the study of disease-associated morphological changes. Moreover, α-13'-COOH is a promising natural compound for the treatment of inflammatory skin diseases.
Topics: Humans; Dermatitis, Atopic; Histamine; Interleukin-8; alpha-Tocopherol; Tocopherols; Skin; Keratinocytes; Cytokines; RNA, Messenger
PubMed: 36615633
DOI: 10.3390/molecules28010440 -
Indian Journal of Pharmacology 2015Lead (Pb) is a long-known poison of environment and industrial origin. Its prolonged exposure affects cellular material and alters cellular genetics and produces...
OBJECTIVE
Lead (Pb) is a long-known poison of environment and industrial origin. Its prolonged exposure affects cellular material and alters cellular genetics and produces oxidative damages. In this study, we investigated the exposure of chronic sustained hypoxia or lead acetate alone or in combination with or without supplementation of α-tocopherol on hepatic oxidative and nitrosative stress in rats.
MATERIALS AND METHODS
The rats weighing 165 ± 5 g were exposed to chronic sustained hypoxia (10% oxygen) or lead acetate (25 mg/kg of body weight, intraperitoneally) alone or in combination with or without supplementation of α-tocopherol (10 mg/100 g b.wt, intramuscularly). The body weight of all the rats was recorded on the day 1 of the treatment and the day of sacrifice. Serum lipid profile was estimated by using a biochemical analyzer. Oxidant and enzymatic antioxidants status was evaluated by using spectrophotometer. Serum levels of hypoxia inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) were measured by using ELISA technique. Histopathological assessments of hepatic tissue were also done.
RESULTS
Exposure of both lead and hypoxia showed decreased body weight, altered serum lipid profile, oxidant and enzymatic antioxidants status, serum HIF-1α and VEGF concentrations. Simultaneous α-tocopherol supplementation showed beneficial effects to all these alterations. Histopathological observations also showed hepatic degenerative changes after lead or hypoxia exposure either alone or in combination, but remarkable improvement has been noticed after α-tocopherol supplementation.
CONCLUSION
Supplementation of α-tocopherol is beneficial to counter both lead acetate and hypoxia induced hepatic cytotoxicities possibly by reducing oxidative and nitrosative stress.
Topics: Animals; Antioxidants; Body Weight; Drug Interactions; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Lipids; Liver Diseases; Male; Organometallic Compounds; Oxidative Stress; Rats; Vascular Endothelial Growth Factor A; alpha-Tocopherol
PubMed: 26069366
DOI: 10.4103/0253-7613.157126 -
Free Radical Biology & Medicine Jan 2014α-Tocopherol is a lipid-soluble antioxidant that is specifically required for reproduction and embryogenesis. However, since its discovery, α-tocopherol's specific... (Review)
Review
α-Tocopherol is a lipid-soluble antioxidant that is specifically required for reproduction and embryogenesis. However, since its discovery, α-tocopherol's specific biologic functions, other than as an antioxidant, and the mechanism(s) mediating its requirement for embryogenesis remain unknown. As an antioxidant, α-tocopherol protects polyunsaturated fatty acids (PUFAs) from lipid peroxidation. α-Tocopherol is probably required during embryonic development to protect PUFAs that are crucial to development, specifically arachidonic (ARA) and docosahexaenoic (DHA) acids. Additionally, ARA and DHA are metabolized to bioactive lipid mediators via lipoxygenase enzymes, and α-tocopherol may directly protect, or it may mediate the production and/or actions of, these lipid mediators. In this review, we discuss how α-tocopherol (1) prevents the nonspecific, radical-mediated peroxidation of PUFAs, (2) functions within a greater antioxidant network to modulate the production and/or function of lipid mediators derived from 12- and 12/15-lipoxygenases, and (3) modulates 5-lipoxygenase activity. The application and implication of such interactions are discussed in the context of α-tocopherol requirements during embryogenesis.
Topics: Abortion, Spontaneous; Animals; Antioxidants; Embryonic Development; Fatty Acids, Unsaturated; Female; Free Radicals; Humans; Lipid Metabolism; Lipid Peroxidation; Lipoxygenases; Pregnancy; Vitamin E Deficiency; alpha-Tocopherol
PubMed: 23920314
DOI: 10.1016/j.freeradbiomed.2013.07.039 -
International Journal of Molecular... Dec 2022MicroRNAs (miRNAs) play a key role in the regulation of genes for normal metabolism in the liver. Dysregulation of miRNAs is involved in the development and progression... (Randomized Controlled Trial)
Randomized Controlled Trial
MicroRNAs (miRNAs) play a key role in the regulation of genes for normal metabolism in the liver. Dysregulation of miRNAs is involved in the development and progression of non-alcoholic fatty liver disease (NAFLD). We aimed to explore changes in circulating miRNA expression in response to delta-tocotrienol (δT3) and alpha-tocopherol (αTF) supplementation and correlate them with relevant biochemical markers in patients with NAFLD. In total, 100 patients with NAFLD were randomized to either receive δT3 ( = 50) 300 mg or αTF ( = 50) 268 mg twice/day for 48 weeks. Plasma expression of miRNA-122, -21, -103a-2, -421, -375 and -34a were determined at baseline, 24 and 48 weeks of intervention using RT-qPCR. Both δT3 and αTF significantly downregulated expression of miRNA-122, -21, -103a-2, -421, -375 and -34a. Moreover, δT3 was more effective than αTF in reducing expression of miRNA-375 and -34a. A significant correlation was observed between miRNA expression and biochemical markers of hepatic steatosis, insulin resistance (IR), oxidative stress (OS), inflammation and apoptosis. δT3 and αTF exert hepato-protective effects by downregulating miRNAs involved in hepatic steatosis, IR, OS, inflammation and apoptosis in patients with NAFLD. Furthermore, δT3 has more pronounced effects than αTF in reducing miR-375 and miR-34a, which are linked to regulation of inflammation and apoptosis.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Circulating MicroRNA; alpha-Tocopherol; Liver; MicroRNAs; Inflammation; Biomarkers; Insulin Resistance
PubMed: 36613525
DOI: 10.3390/ijms24010079 -
Circulation Research Jun 2019Although there has been a long-standing interest in the human health effects of vitamin E, a comprehensive analysis of the association between circulating vitamin E and...
RATIONALE
Although there has been a long-standing interest in the human health effects of vitamin E, a comprehensive analysis of the association between circulating vitamin E and long-term mortality has not been conducted.
OBJECTIVE
Determine whether serum α-tocopherol (the predominant form of vitamin E) is related to long-term overall and cause-specific mortality and elucidate the dose-response relationships with better quantification of the associations.
METHODS AND RESULTS
We conducted a biochemical analysis of 29 092 participants in the ATBC Study (Alpha-Tocopherol, Beta-Carotene Cancer Prevention) that originally tested vitamin E and β-carotene supplementation. Serum α-tocopherol was measured at baseline using high-performance liquid chromatography, and during a 30-year follow-up we identified 23 787 deaths, including deaths from cardiovascular disease (9867), cancer (7687), respiratory disease (2161), diabetes mellitus (119), injuries and accidents (1255), and other causes (2698). After adjusting for major risk factors, we found that men with higher serum α-tocopherol had significantly lower all-cause mortality (hazard ratios=0.83, 0.79, 0.75, and 0.78 for quintile 2 (Q2)-Q5 versus Q1, respectively; P<0.0001), and significantly decreased mortality from cardiovascular disease, heart disease, stroke, cancer, respiratory disease, and other causes, with risk reductions from 17% to 47% for the highest versus lowest quintile. The α-tocopherol association with overall mortality was similar across subgroups of smoking intensity, years of smoking, alcohol consumption, trial supplementation, and duration of follow-up. The association was, however, significantly modified by baseline age and body mass index, with stronger inverse associations for younger men and men with a lower body mass index ( P≤0.006).
CONCLUSIONS
In this long-term prospective cohort study, higher baseline serum α-tocopherol biochemical status was associated with lower risk of overall mortality and mortality from all major causes. Our data support the long-term health benefits of higher serum α-tocopherol for overall and chronic disease mortality and should be replicated in other more diverse populations.
Topics: Aged; Biomarkers; Cardiovascular Diseases; Cause of Death; Cohort Studies; Dietary Supplements; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; alpha-Tocopherol
PubMed: 31219752
DOI: 10.1161/CIRCRESAHA.119.314944 -
Molecules (Basel, Switzerland) Mar 2010Vitamin E is an essential vitamin and a lipid soluble antioxidant, at least, under in vitro conditions. The antioxidant properties of vitamin E are exerted through its... (Review)
Review
Vitamin E is an essential vitamin and a lipid soluble antioxidant, at least, under in vitro conditions. The antioxidant properties of vitamin E are exerted through its phenolic hydroxyl group, which donates hydrogen to peroxyl radicals, resulting in the formation of stable lipid species. Beside an antioxidant role, important cell signalling properties of vitamin E have been described. By using gene chip technology we have identified alpha-tocopherol sensitive molecular targets in vivo including christmas factor (involved in the blood coagulation) and 5alpha-steroid reductase type 1 (catalyzes the conversion of testosterone to 5alpha-dihydrotestosterone) being upregulated and gamma-glutamyl-cysteinyl synthetase (the rate limiting enzyme in GSH synthesis) being downregulated due to alpha-tocopherol deficiency. Alpha-tocopherol regulates signal transduction cascades not only at the mRNA but also at the miRNA level since miRNA 122a (involved in lipid metabolism) and miRNA 125b (involved in inflammation) are downregulated by alpha-tocopherol. Genetic polymorphisms may determine the biological and gene-regulatory activity of alpha-tocopherol. In this context we have recently shown that genes encoding for proteins involved in peripheral alpha-tocopherol transport and degradation are significantly affected by the apoE genotype.
Topics: Animals; Antioxidants; Gene Expression Profiling; Gene Expression Regulation; Homeostasis; Male; MicroRNAs; Polymorphism, Single Nucleotide; Rats; alpha-Tocopherol
PubMed: 20336011
DOI: 10.3390/molecules15031746 -
Scientific Reports Nov 2020Tocopherols, lipid-soluble antioxidants play a crucial role in the antioxidant defense system in higher plants. The antioxidant function of α-tocopherol has been widely...
Tocopherols, lipid-soluble antioxidants play a crucial role in the antioxidant defense system in higher plants. The antioxidant function of α-tocopherol has been widely studied; however, experimental data on the formation of its oxidation products is missing. In this study, we attempt to provide spectroscopic evidence on the detection of oxidation products of α-tocopherol formed by its interaction with singlet oxygen and lipid peroxyl radical. Singlet oxygen was formed using photosensitizer rose bengal and thylakoid membranes isolated from Arabidopsis thaliana. Singlet oxygen reacts with polyunsaturated fatty acid forming lipid hydroperoxide which is oxidized by ferric iron to lipid peroxyl radical. The addition of singlet oxygen to double bond carbon on the chromanol head of α-tocopherol forms α-tocopherol hydroperoxide detected using fluorescent probe swallow-tailed perylene derivative. The decomposition of α-tocopherol hydroperoxide forms α-tocopherol quinone. The hydrogen abstraction from α-tocopherol by lipid peroxyl radical forms α-tocopheroxyl radical detected by electron paramagnetic resonance. Quantification of lipid and protein hydroperoxide from the wild type and tocopherol deficient (vte1) mutant Arabidopsis leaves using a colorimetric ferrous oxidation-xylenol orange assay reveals that α-tocopherol prevents formation of both lipid and protein hydroperoxides at high light. Identification of oxidation products of α-tocopherol might contribute to a better understanding of the protective role of α-tocopherol in the prevention of oxidative damage in higher plants at high light.
Topics: Antioxidants; Arabidopsis; Free Radicals; Hydrogen Peroxide; Light; Lipid Peroxides; Oxidation-Reduction; Oxidative Stress; Singlet Oxygen; Vitamin E; alpha-Tocopherol
PubMed: 33184329
DOI: 10.1038/s41598-020-75634-0 -
Molecules (Basel, Switzerland) Jan 2022Our research aimed to show acrylamide's influence on inflammatory processes, the oxidative stress it causes in the cholinergic system, and the possibility of reducing...
Our research aimed to show acrylamide's influence on inflammatory processes, the oxidative stress it causes in the cholinergic system, and the possibility of reducing inflammation via supplementation with α-tocopherol. For this purpose, an in ovo model was used where the embryos were exposed to acrylamide, α-tocopherol and a cocktail of these substances. After 48 h of exposure, we collected brain samples and performed biochemical assays to examine the effect of the chosen substances on oxidative stress (malondialdehyde-MDA and reduced glutathione-GSH) and acetylcholinesterase activity (AChE). The results showed that acrylamide decreased AChE activity in the examined brain samples by about 25% in comparison to the control group, and this effect was decreased by administering α-tocopherol. The concentration of malondialdehyde significantly increased in the group given acrylamide, while, in the group with α-tocopherol, the observed concentration was lower in comparison to the control group. Moreover, a decrease in glutathione concentration was observed after the administration of acrylamide; however, the protective effect of α-tocopherol was only slightly visible in this case. In conclusion, α-tocopherol minimizes the harmful effects of acrylamide on AchE, and it can minimize the concentration of MDA.
Topics: Acrylamide; Animals; Antioxidants; Brain; Chick Embryo; Chickens; Eggs; Inflammation; Lipid Peroxidation; Malondialdehyde; Oxidative Stress; alpha-Tocopherol
PubMed: 35164231
DOI: 10.3390/molecules27030965