Vitamin E or tocopherol is a fat-soluble vitamin functioning as an antioxidant, protecting the cell membrane. As with all vitamins, the body does not form vitamin E. It solely forms from photosynthetic processes of plants, and therefore must be consumed from outside sources in small quantities. It is found abundantly in olive and sunflower oils, as well as nuts, soybeans, avocados, wheat, and green leafy vegetables.
In the present study, we examined the effect of high fructose-induced metabolic syndrome (MetS) on tissue vitamin E and lipid peroxide (LPO) levels in rats. Feeding of a diet containing 60% fructose (HFD) to Wistar rats for 2, 4, and 6 wk caused week-dependent increases in HOMA-IR score and serum insulin, triglyceride, total cholesterol, and free fatty acid concentrations. Each week HFD feeding increased serum vitamin E concentration. Six-week HFD feeding reduced vitamin E status (the serum ratio of vitamin E/triglyceride+total cholesterol). Four- and 6-wk HFD feeding increased serum LPO concentration. Two-week HFD feeding increased liver, heart, kidney, and skeletal muscle (SM) vitamin E contents and decreased white adipose tissue (WAT) vitamin E content. Four- and 6-wk HFD feeding further reduced WAT vitamin E content without affecting the increased kidney and SM vitamin E contents. Six-week HFD feeding reduced the increased liver and heart vitamin E contents below the level of non-HFD feeding. Four-week HFD feeding increased heart and WAT LPO contents. Six-week HFD feeding increased liver LPO content and further increased heart and WAT LPO contents. Kidney and SM LPO contents remained unchanged. These results indicate that HFD-rats with early MetS have increased liver, kidney, heart, and SM vitamin E contents and decreased WAT vitamin E content under unchanged tissue LPO content and vitamin E status, while HFD-fed rats with progressed MetS have both decreased liver, heart, and WAT vitamin E contents under increased tissue LPO content and disrupted vitamin E status.
“E-cigarettes” are a class of consumer devices designed to deliver drugs, primarily nicotine or marijuana oils, to the lung by vaporization. Regulation of the devices in the United States is relatively minimal, and research on both epidemiology and potential toxicity has focused on nicotine devices. In 2019, an outbreak of an acute respiratory illness in the United States was traced back to the contamination of e-cigarette fluids with vitamin E acetate, which had been used to disguise the dilution of marijuana oils. The outbreak, termed “e-cigarette or vaping associated lung injury” by the U.S. Centers for Disease Control, was characterized by pulmonary infiltrates and hypoxia, which usually required hospitalization and, often, admission to ICUs. The syndrome sickened >2,600 people, mostly young men, and killed >50 people before it began to abate 6 months later. No current regulations exist to prevent a similar event with the same or different chemical contaminants. Absent such regulation, respiratory practitioners should be prepared to evaluate, identify, and treat future cases of acute lung toxicity from e-cigarettes.
Background: Vitamins are commonly used in the prevention of major cardiovascular disease. However, the efficacy and optimum choice remain controversial.
Objective: To compare and rank the relative efficacy among all available vitamin preparations for cardiovascular disease through a network meta-analysis.
Methods: Eligible studies were identified by searching PubMed, Embase, Medline, Cochrane library and Web of Science for randomized controlled trials. A random effects model was applied within a frequentist framework.
Results: Forty-two articles (45 comparisons, 384,248 participants), including nine vitamin interventions, were identified. Vitamin D had the highest probability of being ranked best in effectiveness (0.84 [0.72, 0.98]) on prevention of cardiovascular events. With regard to reducing death of cardiovascular disease rate, vitamin E was considered better efficacy.
Conclusions: Vitamin B, D and E could reduce the incidence of cardiovascular events to varying degrees. At the same time, the combination of vitamins can not show improvement on the efficacy.
Nonalcoholic fatty liver disease (NAFLD) has emerged as the leading liver disease globally. NAFLD patients can have a progressive phenotype, non-alcoholic steatohepatitis (NASH) that could lead to cirrhosis, liver failure and cancer. There is a close bi-directional relationship between NAFLD and type 2 diabetes mellitus (T2DM); NAFLD increases the risk for T2DM and its complications whereas T2DM increases the severity of NAFLD and its complications. The large global impact of NAFLD and T2DM on healthcare systems requires a paradigm shift from specialty care to early identification and risk stratification of NAFLD in primary care and diabetes clinics. Approach to diagnosis, risk stratification and management of NAFLD is discussed. In addition to optimizing the control of coexisting cardiometabolic comorbidities, early referral of NAFLD patients at high risk of having NASH or significant fibrosis to hepatology specialist care may improve management and allow access for clinical trials. Lifestyle modifications, vitamin E, pioglitazone and metformin are currently available options that may benefit patients with T2DM and NAFLD. The burst of clinical trials investigating newer therapeutic agents for NAFLD and NASH offer hope for new, effective and safe therapies in the near future.
Abstract
The pathogenesis of celiac disease (CD) is complex and has not been fully elucidated. It has been postulated that oxidative stress, because of an increase in the concentration of reactive oxygen species and antioxidant capacity reduction, is one of the processes possibly involved in gliadin toxicity. Oxidative imbalance induced by gliadin peptides in enterocytes leads to the activation of the transcription of proinflammatory cytokines and enzymes, such as inducible nitric oxide synthase (iNOS), which in turn causes an increased production of nitric oxide (NO) metabolites favoring oxidative stress. Based on the our previous study, we hypothesized that persistent nitrosative stress despite gluten-free diet (GFD) may be responsible for persistent histopathologic changes and that GFD is only partially able to improve oxidative imbalance. Hence, serum NO levels seem to be useful as a marker of treatment efficacy, and alterations in these levels could indicate CD activity. It is possible that oral antioxidant supplementation may decrease the toxic effects of peptides. In the current study, we aimed to evaluate the effect of treatment with oral vitamin E on oxidative imbalance in adult patients with CD on GFD. For that purpose, we assessed the fasting plasma levels of nitrate as a marker of endogenous NO production and oxidative stress. Moreover, we monitored the individual components of antioxidant capacity. To the best of our knowledge, this is the first study evaluating the effects of oral vitamin E supplementation on oxidative imbalance in patients with CD.
A 5-year-old male neutered domestic shorthair cat suffered from recurrent solitary nodules in different subcutaneous body regions. Nodules were surgically removed and each time histopathological diagnosis was fat necrosis and fibrosing to pyogranulomatous panniculitis. After the second surgery the alpha (α)-tocopherol concentration in serum of the cat was examined and the result (21 mg/L) exceeded the upper limit of the reference interval (3-11 mg/L). Vitamin E amount in diet fed solely in the past was checked as studies have shown that vitamin E amounts in food significantly influence vitamin E concentrations in serum. For comparative purposes, α-tocopherol concentrations were determined in sera of healthy control cats. Additionally, vitamin E amount in wet food from different manufacturers was analysed using gas chromatography coupled to mass spectrometry (GC-MS). The results showed that the diet did not have higher vitamin E amounts compared to other diets. All control cats had similar high serum α-tocopherol concentrations. We conclude that panniculitis can occur despite high serum α-tocopherol concentrations in cats. Further studies are needed to redefine reference values of α-tocopherol in serum of cats.
Radiation therapy remains one of the main treatments for cancer. However, conventional radiotherapy not only manifests a low radiation accumulation in the tumor site, but also displays numerous negative effects. The most serious clinical problem is the radiotherapy resistance leading to cancer deterioration. As an important gaseous signal molecule, nitric oxide (NO) has been widely studied for its role in regulating angiogenesis, improving hypoxia, and inhibiting tumor growth. However, due to the unstable characteristic, the application of NO in cancer therapy is still limited. Here, we designed a micellar system formed by a NO donor, D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS)-NO, for enabling sustained NO release to efficiently deliver NO into the tumor area. TPGS-NO could accumulate in the tumor site for extended circulation, thereby releasing NO to exert antitumor effects and enhance radiotherapy effects under low-oxygen conditions. It demonstrated the increased sensitivity of radiotherapy through enhancing tumor angiogenesis appropriately reducing tumor area hypoxia, which significantly induced tumor cell apoptosis and inhibited its repair during radiation. This work may show great potential in synergistic radiotherapy against cancer by facile NO donor administration.
A novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously quantify phytosterols (brassicasterol, campesterol, stigmasterol and β-sitosterol) and tocopherols (alpha, beta, gamma and delta) entrapped in the lipid bilayer of a liposomal formulation. Apart from liposomes (a pharmaceutical product), the developed method was able to quantify target analytes in agricultural products, thus showing wide applications. Atmospheric pressure chemical ionization (APCI) was employed due to the enhanced ionization of phytosterols and tocopherols in comparison to electrospray ionization. Unlike published work, the chromatographic conditions were modified to simplify the analytical approach. For the first time, a simple isocratic elution (acetonitrile:methanol 99:1 v/v) was utilized for the separation of four phytosterols and four tocopherols in a single run. A substantially better baseline separation of phytosterols were obtained in comparison to reported methods by using poroshell C18 column. The method has a total run time of 7 min, which is the shortest run time among all reported quantitative methods for the simultaneous determination of four phytosterols and four tocopherols. Calibration curves for all phytosterols were linear in the range of 0.05-10 μg/mL. In the case of tocopherols, alpha tocopherol showed linear response in the range of 0.25-10 μg/mL. However, gamma and delta tocopherols exhibited quadratic relationship in the same concentration range (0.25-10 μg/mL). Validation parameters met the International Conference on Harmonization (ICH) guidelines in terms of selectivity, accuracy, precision, repeatability, sensitivity, matrix effects, dilution integrity and stability. The method was, for the first time, successfully applied for the quantifying phytosterols and tocopherols entrapped inside liposomes. An interesting chromatographic phenomenon was observed during sample analysis. Alpha tocopherol (entrapped in the liposomal lipid bilayer) was found to elute at two retention times, 2.53 min and 3.60 min. Such dual separation was not observed in calibration standards and quality controls. It was concluded that the chiral recognition ability of liposomes made up of phosphatidylcholine separated the enantiomers of alpha tocopherol, giving rise to two peaks at two different retention time. To sum, the reported novel LC-MS/MS method addresses three major analytical shortcomings, namely i)longer run time, ii)complex gradient elution and iii)poor baseline separation of phytosterols and tocopherols.
Background: α-tocopherol (AT) and γ-tocotrienol (GT3) are vitamin E isoforms considered to have potential chemopreventive properties. AT has been widely studied in vitro and in clinical trials with mixed results. The latest clinical study (SELECT trial) tested AT in prostate cancer patients, determined that AT provided no benefit, and could promote cancer. Conversely, GT3 has shown antineoplastic properties in several in vitro studies, with no clinical studies published to date. GT3 causes apoptosis via upregulation of the JNK pathway; however, inhibition results in a partial block of cell death. We compared side by side the mechanistic differences in these cells in response to AT and GT3.
Methods: The effects of GT3 and AT were studied on androgen sensitive LNCaP and androgen independent PC-3 prostate cancer cells. Their cytotoxic effects were analyzed via MTT and confirmed by metabolic assays measuring ATP. Cellular pathways were studied by immunoblot. Quantitative analysis and the determination of relationships between cell signaling events were analyzed for both agents tested. Non-cancerous prostate RWPE-1 cells were also included as a control.
Results: The RAF/RAS/ERK pathway was significantly activated by GT3 in LNCaP and PC-3 cells but not by AT. This activation is essential for the apoptotic affect by GT3 as demonstrated the complete inhibition of apoptosis by MEK1 inhibitor U0126. Phospho-c-JUN was upregulated by GT3 but not AT. No changes were observed on AKT for either agent, and no release of cytochrome c into the cytoplasm was detected. Caspases 9 and 3 were efficiently activated by GT3 on both cell lines irrespective of androgen sensitivity, but not in cells dosed with AT. Cell viability of non-cancerous RWPE-1 cells was affected neither by GT3 nor AT.
Conclusions: c-JUN is a recognized master regulator of apoptosis as shown previously in prostate cancer. However, the mechanism of action of GT3 in these cells also include a significant activation of ERK which is essential for the apoptotic effect of GT3. The activation of both, ERK and c-JUN, is required for apoptosis and may suggest a relevant step in ensuring circumvention of mechanisms of resistance related to the constitutive activation of MEK1.