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Vascular Biology (Bristol, England) Jan 2024The impact of α-tocopherol on atherosclerosis is unclear and controversial. While some studies suggest potential benefits, such as antioxidant properties that may...
The impact of α-tocopherol on atherosclerosis is unclear and controversial. While some studies suggest potential benefits, such as antioxidant properties that may reduce oxidative stress, other studies indicate no significant preventive effects. The intricate interplay of various factors, including dosage, individual differences, and study methodologies, contributes to the ongoing uncertainty surrounding α-tocopherol's role in atherosclerosis. Further research is needed to clarify its impact and establish clearer guidelines. Therefore, we aimed to evaluate the impact of α-tocopherol on atherogenesis in ApoE-/- fibrillin (Fbn)1C1039G/+ mice, which is a unique mouse model of advanced atherosclerosis with typical features, such as large necrotic cores, high levels of inflammation, and intraplaque neovascularization, that resemble the unstable phenotype of human plaques. ApoE-/- Fbn1C1039G+/- mice were fed a western-type diet (WD) supplemented with a high dose of α-tocopherol (500 mg/kg diet), while control mice were fed a WD containing a low dose of α-tocopherol (50 mg/kg diet). The high dose of α-tocopherol reduced plaque thickness and necrotic core area in the right common carotid artery (RCCA) after 24 weeks WD. Moreover, α-tocopherol decreased plaque formation and intraplaque neovascularization in the RCCA. In addition to its antiatherogenic effect, chronic supplementation of α-tocopherol improved cardiac function in ApoE-/- Fbn1C1039G/+ mice. However, chronic supplementation of α-tocopherol did not decrease lipid peroxidation. On the contrary, α-tocopherol acted as a prooxidant by increasing plasma levels of oxidized LDL and plaque malondialdehyde, an end product of lipid peroxidation. Our data indicate that α-tocopherol inhibits atherogenesis and improves cardiac function independent of its antioxidant properties.
PubMed: 38717284
DOI: 10.1530/VB-24-0002 -
Antioxidative Effect of Dihydrosphingosine (d18:0) and α-Tocopherol on Tridocosahexaenoin (DHA-TAG).Journal of Agricultural and Food... Oct 2023Sphingoid bases have shown promise as effective antioxidants in fish oils together with α-tocopherol, and the effect has been attributed to products resulting from...
Sphingoid bases have shown promise as effective antioxidants in fish oils together with α-tocopherol, and the effect has been attributed to products resulting from amino-carbonyl reactions (lipation products) between the sphingoid base amine group and carbonyl compounds from lipid oxidation. In this study, the synergistic effect of dihydrosphingosine (d18:0) and α-tocopherol was studied on pure docosahexaenoic acid (DHA) triacylglycerols with an omics-type liquid- and gas-chromatographic mass spectrometric approach to verify the synergistic effect, to get a comprehensive view on the effect of d18:0 on the oxidation pattern, and to identify the lipation products. The results confirmed that d18:0 rapidly reacts further in the presence of lipid oxidation products and α-tocopherol. α-Tocopherol and d18:0 showed an improved antioxidative effect after 12 h of oxidation, indicating the formation of antioxidants through carbonyl-amine reactions. Imines formed from the carbonyls and d18:0 could be tentatively identified.
Topics: Antioxidants; alpha-Tocopherol; Docosahexaenoic Acids; Sphingosine; Oxidation-Reduction
PubMed: 37751317
DOI: 10.1021/acs.jafc.3c02668 -
ACS Omega Jul 2023Soil salinity negatively impacts agricultural productivity. Consequently, strategies should be developed to inculcate a salinity tolerance in crops for sustainable food...
Soil salinity negatively impacts agricultural productivity. Consequently, strategies should be developed to inculcate a salinity tolerance in crops for sustainable food production. Growth regulators play a vital role in regulating salinity stress tolerance. Thus, we examined the effect of exogenous salicylic acid (SA) and alpha-tocopherol (TP) (100 mg/L) on the morphophysio-biochemical responses of two wheat cultivars (Pirsabak-15 and Shankar) to salinity stress (0 and 40 mM). Both Pirsabak-15 and Shankar cultivars were negatively affected by salinity stress. For instance, salinity reduced growth attributes (i.e., leaf fresh and dry weight, leaf moisture content, leaf area ratio, shoot and root dry weight, shoot and root length, as well as root-shoot ratio), pigments (chlorophyll a, chlorophyll a, and carotenoids) but increased hydrogen peroxide (HO), malondialdehyde (MDA), and endogenous TP in both cultivars. Among the antioxidant enzymes, salinity enhanced the activity of peroxidase (POD) and polyphenol oxidase (PPO) in Pirsabak-15; glutathione reductase (GR) and PPO in Shankar, while ascorbate peroxidase (APOX) was present in both cultivars. SA and TP could improve the salinity tolerance by improving growth and photosynthetic pigments and reducing MDA and HO. In general, the exogenous application did not have a positive effect on antioxidant enzymes; however, it increased PPO in Pirsabak-15 and SOD in the Shankar cultivar. Consequently, we suggest that SA and TP could have enhanced the salinity tolerance of our selected wheat cultivars by modulating their physiological mechanisms in a manner that resulted in improved growth. Future molecular studies can contribute to a better understanding of the mechanisms by which SA and TP regulate the selected wheat cultivars underlying salinity tolerance mechanisms.
PubMed: 37521660
DOI: 10.1021/acsomega.3c02166 -
International Journal of Molecular... Jul 2023With the advancement of in vivo studies and clinical trials, the pathogenesis of neurodegenerative diseases has been better understood. However, gaps still need to be... (Review)
Review
With the advancement of in vivo studies and clinical trials, the pathogenesis of neurodegenerative diseases has been better understood. However, gaps still need to be better elucidated, which justifies the publication of reviews that explore the mechanisms related to the development of these diseases. Studies show that vitamin E supplementation can protect neurons from the damage caused by oxidative stress, with a positive impact on the prevention and progression of neurodegenerative diseases. Thus, this review aims to summarize the scientific evidence of the effects of vitamin E supplementation on neuroprotection and on neurodegeneration markers in experimental models. A search for studies published between 2000 and 2023 was carried out in the PubMed, Web of Science, Virtual Health Library (BVS), and Embase databases, in which the effects of vitamin E in experimental models of neurodegeneration were investigated. A total of 5669 potentially eligible studies were identified. After excluding the duplicates, 5373 remained, of which 5253 were excluded after checking the titles, 90 articles after reading the abstracts, and 11 after fully reviewing the manuscripts, leaving 19 publications to be included in this review. Experiments with in vivo models of neurodegenerative diseases demonstrated that vitamin E supplementation significantly improved memory, cognition, learning, motor function, and brain markers associated with neuroregeneration and neuroprotection. Vitamin E supplementation reduced beta-amyloid (Aβ) deposition and toxicity in experimental models of Alzheimer's disease. In addition, it decreased tau-protein hyperphosphorylation and increased superoxide dismutase and brain-derived neurotrophic factor (BDNF) levels in rodents, which seems to indicate the potential use of vitamin E in preventing and delaying the progress of degenerative lesions in the central nervous system.
Topics: Humans; Vitamin E; Neurodegenerative Diseases; Alzheimer Disease; Cognition; Models, Theoretical
PubMed: 37446369
DOI: 10.3390/ijms241311191 -
Biomedicine & Pharmacotherapy =... Jun 2024Spinal cord injury (SCI) is a type of central nervous system (CNS) injury in which ferroptosis is becoming a promising target for treatment. Alpha-tocopherol (Vitamin E,...
Spinal cord injury (SCI) is a type of central nervous system (CNS) injury in which ferroptosis is becoming a promising target for treatment. Alpha-tocopherol (Vitamin E, Vit E) is a compound with anti-ferroptosis activity. The mechanism of alpha-tocopherol in regulating ferroptosis after SCI has not been deeply studied. In this study, rats with SCI were treated by Alpha-tocopherol based on bioinformatic analysis and molecular docking prediction. Behavioral tests and histological findings showed that Alpha-tocopherol promoted neural function recovery and tissue repairment in rats with SCI. Subsequently, regulatory effects of Alpha-tocopherol on Alox15 and ferroptosis were detected and then localized by immunofluorescence. In vitro, alpha-tocopherol improved the ROS accumulation, iron overload, lipid peroxidation and mitochondrial dysfunction. The effects of Alpha-tocopherol on the expression of Alox15, Ptgs2 and 4Hne were validated in vitro. Finally, the inhibitory effects of Alpha-tocopherol on Alox15 and ferroptosis were weakened by the mutation of 87th residue of Alox15. In summary, alpha-tocopherol could alleviate SCI-induced ferroptosis by downregulating Alox15 to promote neural function recovery in rats with SCI. Findings in this study could help further our understanding on SCI-induced ferroptosis and provide a novel insight for treating SCI.
Topics: Animals; Ferroptosis; alpha-Tocopherol; Spinal Cord Injuries; Recovery of Function; Down-Regulation; Rats; Arachidonate 15-Lipoxygenase; Rats, Sprague-Dawley; Lipid Peroxidation; Male; Reactive Oxygen Species; Arachidonate 12-Lipoxygenase; Disease Models, Animal; Molecular Docking Simulation
PubMed: 38754264
DOI: 10.1016/j.biopha.2024.116734 -
Gastric Cancer : Official Journal of... Nov 2023Obesity has been positively associated with gastric cancer. Excess fat impacts hormones, which have been implicated in carcinogenesis. We investigated obesity-related...
BACKGROUND
Obesity has been positively associated with gastric cancer. Excess fat impacts hormones, which have been implicated in carcinogenesis. We investigated obesity-related hormones and cardia gastric cancer (CGC) and non-cardia gastric cancer (NCGC) risk.
METHODS
Nested case-control studies were conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (61 CGCs, and 172 NCGCs and matched controls) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study (100 CGCs and 65 NCGCs and matched controls); serum hormones were measured. In UK-Biobank (n = 458,713), we included 137 CGCs and 92 NCGCs. Sex-specific analyses were conducted. For EPIC and ATBC, odds ratios (ORs), and for UK-Biobank hazard ratios (HRs), were estimated using conditional logistic regression and Cox regression, respectively.
RESULTS
Insulin-like growth-factor-1 was positively associated with CGC and NCGC in EPIC men (OR 1.94, 95% CI 1.03-3.63; OR 1.63, 95% CI 1.05-2.53, respectively), with similar findings for CGC in UK-Biobank women (HR 1.76, 95% CI 1.08-2.88). Leptin in EPIC men and C-peptide in EPIC women were positively associated with NCGC (OR 2.72, 95% CI 1.01-7.34 and OR 2.17, 95% CI 1.19-3.97, respectively). Sex hormone-binding globulin was positively associated with CGC in UK-Biobank men (HR 1.29, 95% CI 1.02-1.64). Conversely, ghrelin was inversely associated with NCGC among EPIC and ATBC men (OR 0.53, 95% CI 0.34-0.84; OR 0.22, 95% CI 0.10-0.50, respectively). In addition, dehydroepiandrosterone was inversely associated with CGC in EPIC and ATBC men combined.
CONCLUSIONS
Some obesity-related hormones influence CGC and NCGC risk.
Topics: Male; Humans; Female; Stomach Neoplasms; Prospective Studies; Cohort Studies; Obesity; Logistic Models; Hormones
PubMed: 37455285
DOI: 10.1007/s10120-023-01414-0 -
Animal Nutrition (Zhongguo Xu Mu Shou... Dec 2023Tocopherol sources in diets are often a combination of -α-tocopheryl acetate (synthetic α-tocopherol) from vitamin supplements and natural tocopherols and 2R-(4'R,...
Tocopherol sources in diets are often a combination of -α-tocopheryl acetate (synthetic α-tocopherol) from vitamin supplements and natural tocopherols and 2R-(4'R, 8'R)-5,7,8-trimethyltocotrienol (α-tocotrienols) from the feed sources. Synthetic α-tocopherol consists of 8 different stereoisomers including 2R-(4'R, 8'R)-5,7,8-trimethyltocol (-α-tocopherol), 2R-(4'S, 8'R)-5,7,8-trimethyltocol (-α-tocopherol), 2R-(4'R, 8'S)-5,7,8-trimethyltocol (-α-tocopherol), 2R-(4'S, 8'S)-5,7,8-trimethyltocol (-α-tocopherol), 2S-(4'S, 8'S)-5,7,8-trimethyltocol (-α-tocopherol), 2S-(4'R, 8'S)-5,7,8-trimethyltocol (-α-tocopherol), 2S-(4'S, 8'R)-5,7,8-trimethyltocol (-α-tocopherol), and 2S-(4'R, 8'R)-5,7,8-trimethyltocol (-α-tocopherol). The pre-absorption metabolism of tocopherols and tocotrienols in ruminants differs from monogastric animals due to the extensive microbial fermentation in the anaerobic rumen. The current study investigated the impact of toasting and decortication of oats on metabolism in the digestive tract (synthesis, digestion), and intestinal digestibility of tocopherols in dairy cows by using 4 ruminal and intestinal cannulated Danish Holstein cows in a 4 × 4 Latin square design for 4 periods. Cows were fed a total mixed ration ad libitum containing different forms of oats: whole oat, decorticated oat, toasted oat, and decorticated toasted oat, all rolled before mixed ration. Overall means across 4 treatments were statistically analyzed, testing whether overall means were different from zero. Decortication or toasting did not affect the balance or digestibility of α-tocopherols in rumen. Average across treatments showed the ruminal degradation of synthetic α-tocopherol (279 mg/d, = 0.02; -value shows that average across treatments is different from zero), synthetic 2R-α-tocopherol (133 mg/d, < 0.01; summation of -, - and -α-tocopherol), and 2S-α-tocopherol (190 mg/d; < 0.01, summation of -, -, , and -α-tocopherol), while -α-tocopherol was formed in the rumen (221 mg/d, = 0.10). The average across treatments showed that small intestinal digestibility of tocopherols ranked in the following order: α-tocotrienol > natural α-tocopherol > synthetic α-tocopherols > 2R-(4'R, 8'R)-,7,8-dimethyltocol (γ-tocopherol). The average across treatments for small intestinal and feed-ileum digestibility ranked in the following order: -α-tocopherol > synthetic 2R-α-tocopherol > 2S-α-tocopherol. Results showed the first evidence for -α-tocopherol formation under anaerobic conditions in the rumen. In addition, synthetic α-tocopherol stereoisomers, γ-tocopherol and α-tocotrienol were degraded in the rumen. There was a discrimination against absorption of synthetic 2R- and 2S-α-tocopherol in the small intestine.
PubMed: 38058569
DOI: 10.1016/j.aninu.2023.07.007 -
Pharmaceutics Jul 2023A novel co-encapsulation system called bicosomes (bicelles within liposomes) has been developed to overcome the limitations associated with the topical application of...
A novel co-encapsulation system called bicosomes (bicelles within liposomes) has been developed to overcome the limitations associated with the topical application of curcumin (cur) and α-tocopherol (α-toc). The physicochemical properties and biological activity in vitro of bicosome systems were evaluated. Bicelles were prepared with DPPC, DHPC, cur, and α-toc (cur/α-toc-bicelles). Liposomal vesicles loading cur/α-toc-bicelles were prepared with Lipoid P-100 and cholesterol-forming cur/α-toc-bicosomes. Three cur/α-toc-bicosomes were evaluated using different total lipid percentages (12, 16, and 20% /). The results indicated that formulations manage to solubilize cur and α-toc in homogeneous bicelles < 20 nm, while the bicosomes reaches 303-420 nm depending on the total lipid percentage in the systems. Bicosomes demonstrated high-encapsulation efficiency (EE) for cur (56-77%) and α-toc (51-65%). The loading capacity (LC) for both antioxidant compounds was 52-67%. In addition, cur/α-toc-bicosomes decreased the lipid oxidation by 52% and increased the antioxidant activity by 60% compared to unloaded bicosomes. The cell viability of these cur/α-toc-bicosomes was >85% in fibroblasts (3T3L1/CL-173™) and ≥65% in keratinocytes (Ha-CaT) and proved to be hematologically compatible. The cur/α-toc-bicelles and cur/α-toc-bicosomes inhibited the growth of in a range between 33 and 76%. Our results propose bicosome systems as a novel carrier able to co-encapsulate, solubilize, protect, and improve the delivery performance of antioxidant molecules. The relevance of these findings is based on the synergistic antioxidant effect of its components, its biocompatibility, and its efficacy for dermal tissue treatment damaged by oxidative stress or by the presence of . However, further studies are needed to assess the efficacy and safety of cur/α-toc bicosomes in vitro and in vivo.
PubMed: 37514098
DOI: 10.3390/pharmaceutics15071912 -
Annals of Medicine Dec 2023Vascular calcification (VC) is one of the complications of chronic kidney disease (CKD) patients. Previous studies have confirmed that oxidative stress (OS) plays an...
BACKGROUND
Vascular calcification (VC) is one of the complications of chronic kidney disease (CKD) patients. Previous studies have confirmed that oxidative stress (OS) plays an important role in developing VC and that antioxidants have anti-VC effects.
OBJECTIVES
Our study aimed to determine the relationship between the intake of antioxidants from dietary sources and the prevalence of VC, especially in the CKD population.
METHODS
This cross-sectional study analyzed population-based data from the National Health and Nutrition Examination Survey (NHANES; 2013-2014). Participants were noninstitutionalized adults >40 years of age. Diet-derived antioxidants were obtained from the first 24-h dietary recall interviews. The abdominal aortic calcification (AAC) score was measured by a DXA scan. We divided the AAC scores into three groups: no calcification (AAC =0), mild to moderate calcification (0< AAC ≤6), and severe calcification (AAC >6).
RESULTS
A total of 2897 participants were included in the main analysis. Our results showed that vitamin B6, α-tocopherol, and lycopene were associated with severe AAC in unadjusted models (odds ratio (OR): 0.81, 95% confidence interval (CI): 0.72-0.91, 0.001; OR: 0.97, 95% CI: 0.95-0.99, 0.008; OR: 0.98, 95% CI: 0.96-0.99, 0.01, respectively). However, only dietary lycopene was associated with severe AAC after adjusting covariates based on clinical and statistical significance. Per 1 mg higher intake of diet-derived lycopene per day, the odds of having severe AAC were 2% lower in the fully adjusted model (OR: 0.98, 95% CI: 0.95-0.999, 0.04). Moreover, in subgroup analysis, diet-derived antioxidant was not associated with AAC in patients with CKD.
UNLABELLED
Our findings indicate that a higher intake of diet-derived lycopene was independently associated with lower odds of having severe AAC in humans. Therefore, a high intake of diet-derived lycopene may help prevent severe AAC.
Topics: Humans; Adult; Nutrition Surveys; Cross-Sectional Studies; Lycopene; Diet; Vascular Calcification; Renal Insufficiency, Chronic; Aortic Diseases; Risk Factors
PubMed: 37014261
DOI: 10.1080/07853890.2023.2195205 -
JCI Insight Jul 2023Vincristine is a widely used chemotherapeutic drug for the treatment of multiple malignant diseases that causes a dose-limiting peripheral neurotoxicity. There is no...
Vincristine is a widely used chemotherapeutic drug for the treatment of multiple malignant diseases that causes a dose-limiting peripheral neurotoxicity. There is no clinically effective preventative treatment for vincristine-induced sensory peripheral neurotoxicity (VIPN), and mechanistic details of this side effect remain poorly understood. We hypothesized that VIPN is dependent on transporter-mediated vincristine accumulation in dorsal root ganglion neurons. Using a xenobiotic transporter screen, we identified OATP1B3 as a neuronal transporter regulating the uptake of vincristine. In addition, genetic or pharmacological inhibition of the murine orthologue transporter OATP1B2 protected mice from various hallmarks of VIPN - including mechanical allodynia, thermal hyperalgesia, and changes in digital maximal action potential amplitudes and neuronal morphology - without negatively affecting plasma levels or antitumor effects of vincristine. Finally, we identified α-tocopherol from an untargeted metabolomics analysis as a circulating endogenous biomarker of neuronal OATP1B2 function, and it could serve as a companion diagnostic to guide dose selection of OATP1B-type transport modulators given in combination with vincristine to prevent VIPN. Collectively, our findings shed light on the fundamental basis of VIPN and provide a rationale for the clinical development of transporter inhibitors to prevent this debilitating side effect.
Topics: Mice; Animals; Vincristine; Xenobiotics; Peripheral Nervous System Diseases; Hyperalgesia; Ganglia, Spinal; Membrane Transport Proteins
PubMed: 37347545
DOI: 10.1172/jci.insight.164646