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Free Radical Biology & Medicine Jul 2014The vitamin E family consists of four tocopherols and four tocotrienols. α-Tocopherol (αT) is the predominant form of vitamin E in tissues and its deficiency leads to... (Review)
Review
The vitamin E family consists of four tocopherols and four tocotrienols. α-Tocopherol (αT) is the predominant form of vitamin E in tissues and its deficiency leads to ataxia in humans. However, results from many clinical studies do not support a protective role of αT in disease prevention in people with adequate nutrient status. On the other hand, recent mechanistic studies indicate that other forms of vitamin E, such as γ-tocopherol (γT), δ-tocopherol, and γ-tocotrienol, have unique antioxidant and anti-inflammatory properties that are superior to those of αT in prevention and therapy against chronic diseases. These vitamin E forms scavenge reactive nitrogen species, inhibit cyclooxygenase- and 5-lipoxygenase-catalyzed eicosanoids, and suppress proinflammatory signaling such as NF-κB and STAT3/6. Unlike αT, other vitamin E forms are significantly metabolized to carboxychromanols via cytochrome P450-initiated side-chain ω-oxidation. Long-chain carboxychromanols, especially 13'-carboxychromanols, are shown to have stronger anti-inflammatory effects than unmetabolized vitamins and may therefore contribute to the beneficial effects of vitamin E forms in vivo. Consistent with mechanistic findings, animal and human studies show that γT and tocotrienols may be useful against inflammation-associated diseases. This review focuses on non-αT forms of vitamin E with respect to their metabolism, anti-inflammatory effects and mechanisms, and in vivo efficacy in preclinical models as well as human clinical intervention studies.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Humans; Vitamin E
PubMed: 24704972
DOI: 10.1016/j.freeradbiomed.2014.03.035 -
Food & Function May 2015Methylglyoxal (MGO) is a highly reactive metabolite of glucose, which is known to cause damage and induce apoptosis in endothelial cells. Endothelial cell damage is...
Methylglyoxal (MGO) is a highly reactive metabolite of glucose, which is known to cause damage and induce apoptosis in endothelial cells. Endothelial cell damage is implicated in the progression of diabetes-associated complications and atherosclerosis. Nuts are high in vitamin E. Consumption of nuts has been recommended for the prevention of cardiovascular disease. However, different nuts contain different forms of vitamin E, which can have different effects on endothelial cells. In this work, we investigated the protective effect of different isoforms of vitamin E on MGO-induced apoptosis in human umbilical vein endothelial cells (HUVECs). Among all forms of vitamin E, δ-tocopherol showed the highest effect on apoptosis of HUVECs. We also compared the anti-apoptotic activity of δ-tocopherol with that of α-tocopherol in MGO-treated HUVECs. Pretreatment with α- or δ-tocopherol significantly inhibited MGO-induced changes in cell morphology, cell death, and production of intracellular reactive oxygen species. δ-Tocopherol prevented MGO-induced apoptosis in HUVECs by increasing Bcl-2 expression and decreasing Bax expression. Interestingly, α-tocopherol also inhibited these factors but to a lesser extent than δ-tocopherol. MGO was found to activate mitogen-activated protein kinases (MAPKs). Compared to pretreatment with α-tocopherol, pretreatment with δ-tocopherol more strongly inhibited the activation of MAPKs, such as JNK and ERK1/2. These findings suggest that δ-tocopherol may be a more effective regulator of MGO-induced apoptosis than α-tocopherol.
Topics: Apoptosis; Human Umbilical Vein Endothelial Cells; Humans; Mitogen-Activated Protein Kinases; Oxidative Stress; Proto-Oncogene Proteins c-bcl-2; Pyruvaldehyde; Reactive Oxygen Species; Signal Transduction; Tocopherols
PubMed: 25832198
DOI: 10.1039/c4fo01110d -
Antioxidants (Basel, Switzerland) Dec 2022During the last years, the formalism of the pseudophase kinetic model (PKM) has been successfully applied to determine the distributions of antioxidants and their...
Distributions of α- and δ-TOCopherol in Intact Olive and Soybean Oil-in-Water Emulsions at Various Acidities: A Test of the Sensitivity of the Pseudophase Kinetic Model.
During the last years, the formalism of the pseudophase kinetic model (PKM) has been successfully applied to determine the distributions of antioxidants and their effective interfacial concentrations, and to assess the relative importance of emulsion and antioxidant properties (oil and surfactant nature, temperature, acidity, chemical structure, hydrophilic-liphophilic balance (HLB), etc.) on their efficiency in intact lipid-based emulsions. The PKM permits separating the contributions of the medium and of the concentration to the overall rate of the reaction. In this paper, we report the results of a specifically designed experiment to further test the suitability of the PKM to evaluate the distributions of antioxidants among the various regions of intact lipid-based emulsions and provide insights into their chemical reactivity in multiphasic systems. For this purpose, we employed the antioxidants α- and δ-TOCopherol (α- and δ-TOC, respectively) and determined, at different acidities well below their pa, the interfacial rate constants for the reaction between 16-ArN and α- and δ-TOC, and the antioxidant distributions in intact emulsions prepared with olive and soybean oils. Results show that the effective interfacial concentration of δ-TOC is higher than that of α-TOC in 1:9 (/) soybean and 1:9 olive oil emulsions. The effective interfacial concentrations of tocopherols are much higher (15-96-fold) than the stoichiometric concentrations, as the effective interfacial concentrations of both δ-TOC and α-TOC in soybean oil emulsions are higher (2-fold) than those in olive oil emulsions. Overall, the results demonstrate that the PKM grants an effective separation of the medium and concentration effects, demonstrating that the PKM constitutes a powerful non-destructive tool to determine antioxidant concentrations in intact emulsions and to assess the effects of various factors affecting them.
PubMed: 36552687
DOI: 10.3390/antiox11122477 -
Antioxidants (Basel, Switzerland) May 2023Charged interfaces may play an important role in the fate of chemical reactions. Alterations in, for instance, the interfacial acidity of emulsions induced by the charge...
Charged interfaces may play an important role in the fate of chemical reactions. Alterations in, for instance, the interfacial acidity of emulsions induced by the charge of the surfactant head group and associated counterions may change the ionization status of antioxidants, modifying their effective concentrations. The chemical reactivity between interfacial reactants and charged species of opposite charge (protons, metallic ions, etc.) is usually interpreted in terms of pseudophase ion-exchange models, treating the distribution of charged species in terms of partitioning and ion exchange. Here, we focus on analyzing the effects of charged interfaces on the oxidative stability of soybean oil-in-water (o/w) emulsions prepared with anionic (sodium dodecyl sulfate, SDS), cationic (cetyltrimethylammonium bromide, CTAB) and neutral (Tween 20) surfactants, and some of their mixtures, in the presence and absence of δ-tocopherol (δ-TOC). We have also determined the effective concentrations of δ-TOC in the oil, interfacial and aqueous regions of the intact emulsions. In the absence of δ-TOC, the relative oxidative stability order was CTAB < TW20 ~ TW20/CTAB < SDS. Surprisingly, upon the addition of δ-TOC, the relative order was SDS ≈ TW20 << TW20/CTAB < CTAB. These apparently surprising results can be rationalized in terms of the nice correlation that exists between the relative oxidative stability and the effective interfacial concentrations of δ-TOC in the various emulsions. The results emphasize the importance of considering the effective interfacial concentrations of antioxidants in interpreting their relative efficiency in emulsions.
PubMed: 37371888
DOI: 10.3390/antiox12061158 -
Cancer Prevention Research... Mar 2011In contrast to strong epidemiologic, preclinical, and secondary clinical evidence for vitamin E (tocopherols) in reducing cancer risk, large-scale clinical...
In contrast to strong epidemiologic, preclinical, and secondary clinical evidence for vitamin E (tocopherols) in reducing cancer risk, large-scale clinical cancer-prevention trials of α-tocopherol have been negative. This vexing contrast helped spur substantial preclinical efforts to better understand and improve the antineoplastic activity of tocopherol through, for example, the study of different tocopherol forms. We previously showed that the γ-tocopherol-rich mixture (γ-TmT) effectively inhibited colon and lung carcinogenesis and the growth of transplanted lung-cancer cells in mice. We designed this study to determine the relative activities of different forms of tocopherol in a xenograft model, comparing the anticancer activities of δ-tocopherol with those of α- and γ-tocopherols. We subcutaneously injected human lung cancer H1299 cells into NCr nu/nu mice, which then received α-, γ-, or δ-tocopherol or γ-TmT in the diet (each at 0.17% and 0.3%) for 49 days. δ-Tocopherol inhibited tumor growth most strongly. γ-Tocopherol and γ-TmT (at 0.3%) also inhibited growth significantly, but α-tocopherol did not. δ-Tocopherol also effectively decreased oxidative DNA damage and nitrotyrosine formation and enhanced apoptosis in tumor cells; again, γ-tocopherol also was active in these regards but less so, and α-tocopherol was not. Each supplemented diet increased serum levels of its tocopherol - up to 45 μmol/L for α-tocopherol, 9.7 μmol/L for γ-tocopherol, and 1.2 μmol/L for δ-tocopherol; dietary γ- or δ-tocopherol, however, decreased serum α-tocopherol levels, and dietary α-tocopherol decreased serum levels of γ-tocopherol. Each dietary tocopherol also increased its corresponding side-chain-degradation metabolites, with concentrations of δ-tocopherol metabolites greater than γ-tocopherol and far greater than α-tocopherol metabolites in serum and tumors. This study is the first in vivo assessment of δ-tocopherol in tumorigenesis and shows that δ-tocopherol is more active than α- or γ-tocopherol in inhibiting tumor growth, possibly through trapping reactive oxygen and nitrogen species and inducing apoptosis; δ-tocopherol metabolites could contribute significantly to these results.
Topics: Animals; Anticarcinogenic Agents; Apoptosis; Cell Line, Tumor; DNA Damage; Humans; Lung Neoplasms; Male; Mice; Neoplasm Transplantation; Reactive Nitrogen Species; Reactive Oxygen Species; Tocopherols; Tyrosine; alpha-Tocopherol; gamma-Tocopherol
PubMed: 21372040
DOI: 10.1158/1940-6207.CAPR-10-0130 -
Pharmacology & Therapeutics Jun 2016The discovery of vitamin E (α-tocopherol) began in 1922 as a vital component required in reproduction. Today, there are eight naturally occurring vitamin E isoforms,... (Review)
Review
The discovery of vitamin E (α-tocopherol) began in 1922 as a vital component required in reproduction. Today, there are eight naturally occurring vitamin E isoforms, namely α-, β-, γ- and δ-tocopherol and α-, β-, γ- and δ-tocotrienol. Vitamin E is potent antioxidants, capable of neutralizing free radicals directly by donating hydrogen from its chromanol ring. α-Tocopherol is regarded the dominant form in vitamin E as the α-tocopherol transfer protein in the liver binds mainly α-tocopherol, thus preventing its degradation. That contributed to the oversight of tocotrienols and resulted in less than 3% of all vitamin E publications studying tocotrienols. Nevertheless, tocotrienols have been shown to possess superior antioxidant and anti-inflammatory properties over α-tocopherol. In particular, inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase to lower cholesterol, attenuating inflammation via downregulation of transcription factor NF-κB activation, and potent radioprotectant against radiation damage are some properties unique to tocotrienols, not tocopherols. Aside from cancer, vitamin E has also been shown protective in bone, cardiovascular, eye, nephrological and neurological diseases. In light of the different pharmacological properties of tocopherols and tocotrienols, it becomes critical to specify which vitamin E isoform(s) are being studied in any future vitamin E publications. This review provides an update on vitamin E therapeutic potentials, protective effects and modes of action beyond cancer, with comparison of tocopherols against tocotrienols. With the concerted efforts in synthesizing novel vitamin E analogs and clinical pharmacology of vitamin E, it is likely that certain vitamin E isoform(s) will be therapeutic agents against human diseases besides cancer.
Topics: Animals; Antioxidants; Biological Availability; Humans; Neoplasms; Vitamin E
PubMed: 26706242
DOI: 10.1016/j.pharmthera.2015.12.003 -
The Journal of Biological Chemistry Nov 2012Niemann-Pick disease type C (NPC) and Wolman disease are two members of a family of storage disorders caused by mutations of genes encoding lysosomal proteins....
Niemann-Pick disease type C (NPC) and Wolman disease are two members of a family of storage disorders caused by mutations of genes encoding lysosomal proteins. Deficiency in function of either the NPC1 or NPC2 protein in NPC disease or lysosomal acid lipase in Wolman disease results in defective cellular cholesterol trafficking. Lysosomal accumulation of cholesterol and enlarged lysosomes are shared phenotypic characteristics of both NPC and Wolman cells. Utilizing a phenotypic screen of an approved drug collection, we found that δ-tocopherol effectively reduced lysosomal cholesterol accumulation, decreased lysosomal volume, increased cholesterol efflux, and alleviated pathological phenotypes in both NPC1 and Wolman fibroblasts. Reduction of these abnormalities may be mediated by a δ-tocopherol-induced intracellular Ca(2+) response and subsequent enhancement of lysosomal exocytosis. Consistent with a general mechanism for reduction of lysosomal lipid accumulation, we also found that δ-tocopherol reduces pathological phenotypes in patient fibroblasts from other lysosomal storage diseases, including NPC2, Batten (ceroid lipofuscinosis, neuronal 2, CLN2), Fabry, Farber, Niemann-Pick disease type A, Sanfilippo type B (mucopolysaccharidosis type IIIB, MPSIIIB), and Tay-Sachs. Our data suggest that regulated exocytosis may represent a potential therapeutic target for reduction of lysosomal storage in this class of diseases.
Topics: Animals; Calcium; Calcium Signaling; Cell Line; Cholesterol; Cricetinae; Exocytosis; Humans; Lipid Metabolism; Lysosomes; Niemann-Pick Disease, Type C; Tocopherols; Tripeptidyl-Peptidase 1; Wolman Disease
PubMed: 23035117
DOI: 10.1074/jbc.M112.357707 -
Molecules (Basel, Switzerland) Oct 2020This investigation included the chemical analysis of () seed oil and its antifungal properties against 10 fungal species. Seed oils of six populations were analyzed...
This investigation included the chemical analysis of () seed oil and its antifungal properties against 10 fungal species. Seed oils of six populations were analyzed using high performance liquid chromatography (HPLC) and gas chromatograph/mass spectrometry (GC-MS). The HPLC analysis indicated that . seed oil exhibited a very high level of tocopherol contents, with values in the range of 2385.66-2722.68 mg/100 g. The most abundant tocopherol isomer was δ-tocopherol (90.39%), followed by γ-tocopherol (8.08%) and α-tocopherol (1.14%). We discovered for the first time the presence of tocotrenols in seed oils of the six populations studied. The GC-MS analyses revealed that linoleic acid was the main fatty acid (65.17%), followed by oleic acid (23.12%), palmitic acid (5.36%) and stearic acid (3.08%). We also studied the antifungal activity of seed oil of the Medenine (MD) population on ten fungal pathogens. The antifungal effects differed among pathogens and depended on oil concentrations. Seed oil of the MD population caused a significant decrease in mycelial growth of all fungi tested, with values ranging 31.50-82.11%, except for sp., which showed no inhibition. The antifungal activity against the 10 selected fungi can be explained by the richness in tocols of the extracted oil and make a promising crop for biological control. Furthermore, the importance of fatty acids and the wide geographic spread in Tunisia of this species make this crop a potential source of renewable energy.
Topics: Antifungal Agents; Fungi; Gas Chromatography-Mass Spectrometry; Linoleic Acid; Oleic Acid; Palmitic Acid; Peganum; Plant Oils; Seeds; Tocopherols
PubMed: 33036316
DOI: 10.3390/molecules25194569 -
Molecular Nutrition & Food Research Jun 2016Tocopherols exist in four forms designated as α, β, δ, and γ. Due to their strong antioxidant properties, tocopherols have been suggested to reduce the risk of... (Review)
Review
Tocopherols exist in four forms designated as α, β, δ, and γ. Due to their strong antioxidant properties, tocopherols have been suggested to reduce the risk of cancer. Cancer prevention studies with tocopherols have mostly utilized α-tocopherol. Large-scale clinical trials with α-tocopherol provided inconsistent results regarding the cancer-preventive activities of tocopherols. This review summarizes our current understanding of the anticancer activities of different forms of tocopherols based on follow-up of the clinical trials, recent epidemiological evidences, and experimental studies using in vitro and in vivo models. The experimental data provide strong evidence in support of the anticancer activities of δ-tocopherol, γ-tocopherol, and the natural tocopherol mixture rich in γ-tocopherol, γ-TmT, over α-tocopherol. Such outcomes emphasize the need for detailed investigation into the cancer-preventive activities of different forms of tocopherols to provide a strong rationale for intervention studies in the future.
Topics: Animals; Anticarcinogenic Agents; Antioxidants; Cell Line, Tumor; Disease Models, Animal; Humans; Meta-Analysis as Topic; Neoplasms; Randomized Controlled Trials as Topic; Tocopherols
PubMed: 26751721
DOI: 10.1002/mnfr.201500847