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Molecular Carcinogenesis Apr 2020α-Tocopherol (α-T) is the major form of vitamin E (VE) in animals and has the highest activity in carrying out the essential antioxidant functions of VE. Because of... (Review)
Review
α-Tocopherol (α-T) is the major form of vitamin E (VE) in animals and has the highest activity in carrying out the essential antioxidant functions of VE. Because of the involvement of oxidative stress in carcinogenesis, the cancer prevention activity of α-T has been studied extensively. Lower VE intake or nutritional status has been shown to be associated with increased cancer risk, and supplementation of α-T to populations with VE insufficiency has shown beneficial effects in lowering the cancer risk in some intervention studies. However, several large intervention studies with α-T conducted in North America have not demonstrated a cancer prevention effect. More recent studies have centered on the γ- and δ-forms of tocopherols and tocotrienols (T3). In comparison with α-T, these forms have much lower systemic bioavailability but have shown stronger cancer-preventive activities in many studies in animal models and cell lines. γ-T3 and δ-T3 generally have even higher activities than γ-T and δ-T. In this article, we review recent results from human and laboratory studies on the cancer-preventive activities of different forms of tocopherols and tocotrienols, at nutritional and pharmacological levels. We aim to elucidate the possible mechanisms of the preventive actions and discuss the possible application of the available information for human cancer prevention by different VE forms.
Topics: Animals; Antioxidants; Carcinogenesis; Dietary Supplements; Humans; Neoplasms; Oxidation-Reduction; Oxidative Stress; Tocopherols; Vitamin E
PubMed: 32017273
DOI: 10.1002/mc.23160 -
European Annals of Otorhinolaryngology,... Dec 2014Osteoradionecrosis (ORN) is a severe, generally irreversible complication of radiotherapy due to failure of healing. The pentoxifylline-tocopherol combination decreases...
INTRODUCTION
Osteoradionecrosis (ORN) is a severe, generally irreversible complication of radiotherapy due to failure of healing. The pentoxifylline-tocopherol combination decreases the superficial fibrosis induced by radiotherapy. Potentiation by Clodronate (PENTOCLO) appears to be effective in ORN of the mandible. The objectives of this study were to evaluate the efficacy and safety of PENTOCLO to treat osteoradionecrosis of the mandible.
METHODS
Retrospective study of 27 patients with a mean age of 65±12 years, managed for ORN of the mandible secondary to irradiation for head and neck cancer, treated by the PENTOCLO protocol between January 2010 and March 2011. The primary endpoint was regression of exposed bone until complete healing. Assessment was both clinical (measurement of mucosal ulceration) and radiological (panoramic dental x-rays) before treatment, after antibiotic-corticosteroid combination therapy for one month (M1), and then after 3, 6, 12 months of PENTOCLO.
RESULTS
An improvement of mucosal ulceration was observed in 16/21 patients after 3 months and in 12/17 patients after 6 months of PENTOCLO. Healing was obtained in 16 patients. Median healing time was 82 days (range: 32-266), and was shorter after surgery and radiotherapy (49 days) and longer after chemoradiotherapy (169 days). Radiological healing was achieved later than clinical healing with improvement in 9 out of 20 patients at 3 months. The safety and efficacy of treatment were evaluated by intraoral clinical examination, and assessment of feeding, weight and analgesic consumption. No patient discontinued treatment because of adverse effects.
CONCLUSION
The PENTOCLO protocol achieved clinical and radiological regression of ORN with, in parallel, a reduction of the indications for major surgery. These preliminary results need to be confirmed by prospective studies comprising quality of life assessment.
Topics: Aged; Aged, 80 and over; Bone Density Conservation Agents; Clodronic Acid; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Mandibular Diseases; Middle Aged; Oral Ulcer; Osteoradionecrosis; Pentoxifylline; Radiography, Panoramic; Retrospective Studies; Tocopherols; Wound Healing
PubMed: 24993781
DOI: 10.1016/j.anorl.2013.11.006 -
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 -
Nutrients Jul 2023The relationship between vitamin E intake or circulating α-tocopherol and various health outcomes is still debatable and uncertain. We conducted an umbrella review to... (Review)
Review
The relationship between vitamin E intake or circulating α-tocopherol and various health outcomes is still debatable and uncertain. We conducted an umbrella review to identify the relationships between vitamin E intake or circulating tocopherol and health outcomes by merging and recalculating earlier meta-analyses. The connections that were found to be statistically significant were then classified into different evidence levels based on values, between-study heterogeneity, prediction intervals, and small study effects. We finally included 32 eligible meta-analyses with four vitamin E sources and 64 unique health outcomes. Only the association between circulating α-tocopherol and wheeze or asthma in children was substantiated by consistent evidence. Suggestive evidence was suggested for seven results on endothelial function (supplemental vitamin E): serum C-reactive protein (CRP) concentrations (supplemental vitamin E), cervical cancer (dietary vitamin E), esophageal cancer (dietary vitamin E), cervical intraepithelial neoplasia (CIN, dietary vitamin E), pancreatic cancer (total vitamin E intake), and colorectal cancer (circulating α-tocopherol levels); all of these showed a protective effect consistent with the vitamin E source. In conclusion, our work has indicated that vitamin E is protective for several particular health outcomes. Further prospective studies are required when other factors that may contribute to bias are considered.
Topics: Child; Humans; Vitamin E; alpha-Tocopherol; Antioxidants; Tocopherols; Diet
PubMed: 37571239
DOI: 10.3390/nu15153301 -
Molecules (Basel, Switzerland) Mar 2022Cisplatin (CP) is a conventional chemotherapeutic agent with serious adverse effects. Its toxicity was linked to the stimulation of oxidative stress and inflammation. As...
Cisplatin (CP) is a conventional chemotherapeutic agent with serious adverse effects. Its toxicity was linked to the stimulation of oxidative stress and inflammation. As a result, this study explored the protective effect of baicalein and alpha-tocopherol in nephrotoxicity induced by cisplatin. Until receiving an intraperitoneal injection of CP (3 mg/kg BW), rats were given baicalein orally 100 mg/kg for seven days or/and a single intraperitoneal injection of α-tocopherol 250 mg/kg. Renal function was tested to explore whether baicalein and α-tocopherol have any beneficial effects; blood urea nitrogen (BUN), serum creatinine, malondialdehyde (MDA) content, antioxidant activity biomarkers and histopathology of renal tissue, oxidative stress biomarkers, inflammatory response markers, and histopathological features of kidney architecture were measured. Cisplatin treatment resulted in extreme renal failure, as measured by high serum creatinine and BUN levels and severe renal changes. Cisplatin therapy resulted in increased lipid peroxidation and decreased glutathione and superoxide dismutase levels, reflecting oxidative stress. Upon treatment with α-tocopherol, baicalein, and combined therapy, there was augmentation in the antioxidant status as well as a reduction in IL-6, NF-κB, TNF, TLR2, and TLR4 and a significant increase in Keap-1 and NRF-2. The combined treatment was the most effective and the nearest to the normal status. These findings suggest that baicalein and α-tocopherol may be useful in preventing cisplatin-induced nephrotoxicity.
Topics: Animals; Antineoplastic Agents; Antioxidants; Biomarkers; Blood Urea Nitrogen; Cisplatin; Creatinine; Flavanones; Kidney; Oxidative Stress; Rats; Renal Insufficiency; Tocopherols; Toll-Like Receptors; alpha-Tocopherol
PubMed: 35408581
DOI: 10.3390/molecules27072179 -
Molecules (Basel, Switzerland) Oct 2022Grape pomace and seeds are important winemaking by-products. Their oils are rich in bioactive compounds such as fatty acids and tocopherols. We have characterized oils...
Grape pomace and seeds are important winemaking by-products. Their oils are rich in bioactive compounds such as fatty acids and tocopherols. We have characterized oils from both by-products from five Spanish grape varieties (Palomino Fino, Pedro Ximénez, Muscat of Alexandria, Tempranillo and Tintilla de Rota). A high content of UFAs was found in all the analyzed samples. Grape pomace oils generally had the same oleic acid (PUFA) content as seed oils, and lower PUFA contents; they also had a markedly higher linolenic acid (PUFA) content, improving the PUFA/PUFA ratio. All the oil studied show good indicators of nutritional quality: low values of the atherogenicity (0.112-0.157 for pomace, 0.097-0.112 for seed) and thrombogenicity indices (0.30-0.35 for pomace, 0.28-0.31 for seed) and high values of the relationship between hypo- and hypercholesterolemic fatty acids (6.93-9.45 for pomace, 9.11-10.54 for seed). Three tocopherols were determined: α-, γ- and δ-tocopherol. Pomace oils have higher relative contents of α- and δ-tocopherol, whereas seed oils have higher relative contents of γ-tocopherol. A significantly higher content of total tocopherols has been found in pomace oil; it is higher in the oils from red varieties of pomace (628.2 and 706.6 mg/kg by-product), and in the oils from pomace containing stems (1686.4 mg/kg by-product). All the oils obtained can be considered as a source of vitamin E, and their consumption is beneficial for health.
Topics: Tocopherols; Fatty Acids; Vitis; gamma-Tocopherol; Spain; Plant Oils; Seeds; Vitamin E; alpha-Linolenic Acid; Oleic Acid
PubMed: 36296576
DOI: 10.3390/molecules27206980 -
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 -
Journal of Immunology (Baltimore, Md. :... Nov 2022In humans and mice, offspring of allergic mothers are predisposed to development of allergy. In mice, allergic mothers have elevated β-glucosylceramides (βGlcCers)...
In humans and mice, offspring of allergic mothers are predisposed to development of allergy. In mice, allergic mothers have elevated β-glucosylceramides (βGlcCers) that are transported to the fetus via the placenta and to offspring via milk. The elevated βGlcCers increase the number of fetal liver CD11c+CD11b+ dendritic cells (DCs) and offspring allergen-induced lung eosinophilia. These effects are modifiable by maternal dietary supplementation with the plant-derived lipids α-tocopherol and γ-tocopherol. It is not known whether βGlcCers and tocopherols directly regulate development of DCs. In this study, we demonstrated that βGlcCers increased development of GM-CSF-stimulated mouse bone marrow-derived DCs (BMDCs) in vitro without altering expression of costimulatory molecules. This increase in BMDC numbers was blocked by α-tocopherol and potentiated by γ-tocopherol. Furthermore, βGlcCers increased protein kinase Cα (PKCα) and PKCδ activation in BMDCs that was blocked by α-tocopherol. In contrast, γ-tocopherol increased BMDC PKCα and PKCδ activation and enhanced the βGlcCer-induced increase in PKCδ activation in a DC subset. Ag processing per DC was minimally enhanced in βGlcCer-treated BMDCs and not altered ex vivo in lung DCs from pups of allergic mothers. Pups of allergic mothers had an increased proportion of CD11b+CD11c+ subsets of DCs, contributing to enhanced stimulation of T cell proliferation ex vivo. Thus, βGlcCer, which is both necessary and sufficient for development of allergic predisposition in offspring of allergic mothers, directly increased development and PKC activation in BMDCs. Furthermore, this was modifiable by dietary tocopherols. This may inform design of future studies for the prevention or intervention in asthma and allergic disease.
Topics: Humans; Female; Pregnancy; Animals; Mice; Tocopherols; gamma-Tocopherol; Glucosylceramides; alpha-Tocopherol; Protein Kinase C-alpha; Hypersensitivity; Asthma; CD11c Antigen; Dendritic Cells
PubMed: 36426950
DOI: 10.4049/jimmunol.2101188 -
International Journal of Molecular... Jun 2021Tocopherols and tocotrienols are natural compounds of plant origin, available in the nature. They are supplied in various amounts in a diet, mainly from vegetable oils,... (Review)
Review
Tocopherols and tocotrienols are natural compounds of plant origin, available in the nature. They are supplied in various amounts in a diet, mainly from vegetable oils, some oilseeds, and nuts. The main forms in the diet are α- and γ-tocopherol, due to the highest content in food products. Nevertheless, α-tocopherol is the main form of vitamin E with the highest tissue concentration. The α- forms of both tocopherols and tocotrienols are considered as the most metabolically active. Currently, research results indicate also a greater antioxidant potential of tocotrienols than tocopherols. Moreover, the biological role of vitamin E metabolites have received increasing interest. The aim of this review is to update the knowledge of tocopherol and tocotrienol bioactivity, with a particular focus on their bioavailability, distribution, and metabolism determinants in humans. Almost one hundred years after the start of research on α-tocopherol, its biological properties are still under investigation. For several decades, researchers' interest in the biological importance of other forms of vitamin E has also been growing. Some of the functions, for instance the antioxidant functions of α- and γ-tocopherols, have been confirmed in humans, while others, such as the relationship with metabolic disorders, are still under investigation. Some studies, which analyzed the biological role and mechanisms of tocopherols and tocotrienols over the past few years described new and even unexpected cellular and molecular properties that will be the subject of future research.
Topics: Antioxidants; Diet; Humans; Tocotrienols; alpha-Tocopherol; gamma-Tocopherol
PubMed: 34207571
DOI: 10.3390/ijms22126222 -
Free Radical Biology & Medicine Feb 2022Asthma and allergic disease result from interactions of environmental exposures and genetics. Vitamin E is one environmental factor that can modify development of...
Asthma and allergic disease result from interactions of environmental exposures and genetics. Vitamin E is one environmental factor that can modify development of allergy early in life and modify responses to allergen after allergen sensitization. Seemingly varied outcomes from vitamin E are consistent with the differential functions of the isoforms of vitamin E. Mechanistic studies demonstrate that the vitamin E isoforms α-tocopherol and γ-tocopherol have opposite functions in regulation of allergic inflammation and development of allergic disease, with α-tocopherol having anti-inflammatory functions and γ-tocopherol having pro-inflammatory functions in allergy and asthma. Moreover, global differences in prevalence of asthma by country may be a result, at least in part, of differences in consumption of these two isoforms of tocopherols. It is critical in clinical and animal studies that measurements of the isoforms of tocopherols be determined in vehicles for the treatments, and in the plasma and/or tissues before and after intervention. As allergic inflammation is modifiable by tocopherol isoforms, differential regulation by tocopherol isoforms provide a foundation for development of interventions to improve lung function in disease and raise the possibility of early life dietary interventions to limit the development of lung disease.
Topics: Animals; Asthma; Hypersensitivity; Tocopherols; Vitamin E; alpha-Tocopherol; gamma-Tocopherol
PubMed: 34785320
DOI: 10.1016/j.freeradbiomed.2021.10.037