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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 -
Free Radical Biology & Medicine Aug 2024α-Tocopherol (α-T) is a vitamin, but the reasons for the α-T requirement are controversial. Given that α-T deficiency was first identified in embryos, we studied to...
α-Tocopherol (α-T) is a vitamin, but the reasons for the α-T requirement are controversial. Given that α-T deficiency was first identified in embryos, we studied to the premier model of vertebrate embryo development, the zebrafish embryo. We developed an α-T-deficient diet for zebrafish and used fish consuming this diet to produce α-T deficient (E-) embryos. We showed that α-T deficiency causes increased lipid peroxidation, leading to metabolic dysregulation that impacts both biochemical and morphological changes at very early stages in development. These changes occur at an early developmental window, which takes place prior to an analogous time to when a human knows she is pregnant. We found that α-T limits the chain reaction of lipid peroxidation and protects metabolic pathways and integrated gene expression networks that control embryonic development. Importantly, not only is α-T critical during early development, but the neurodevelopmental process is highly dependent on α-T trafficking by the α-T transfer protein (TTPa). Data from both gene expression and evaluation of the metabolome in E- embryos suggest that the activity of the mechanistic Target of Rapamycin (mTOR) signaling pathway is dysregulated-mTOR is a master regulatory mechanism, which controls both metabolism and neurodevelopment. Our findings suggest that TTPa is needed not only for regulation of plasma α-T in adults but is a key regulator during embryogenesis.
Topics: Animals; Female; Humans; alpha-Tocopherol; Carrier Proteins; Embryo, Nonmammalian; Embryonic Development; Gene Expression Regulation, Developmental; Lipid Peroxidation; Signal Transduction; TOR Serine-Threonine Kinases; Zebrafish; Zebrafish Proteins; Pregnancy
PubMed: 38754744
DOI: 10.1016/j.freeradbiomed.2024.05.028 -
Cureus Dec 2023Background Diclofenac (DCF), a nonsteroidal anti-inflammatory drug (NSAID), is widely used for its analgesic and anti-inflammatory properties, but it can also be...
Background Diclofenac (DCF), a nonsteroidal anti-inflammatory drug (NSAID), is widely used for its analgesic and anti-inflammatory properties, but it can also be nephrotoxic. Vitamin E (α-tocopherol) has been shown to protect against renal toxicity caused by various agents, including NSAIDs. This study aims to evaluate the pathophysiology of renal damage and the nephroprotective effect of vitamin E against DCF-induced renal damage in male Wistar rats. Animal and methods Twenty-four male Wistar rats, divided into six equal groups, were used for the study. Group 1 (control group) was treated with distilled water only, while the other groups received either high or low doses of DCF with or without a fixed dose of vitamin E. Renal function was assessed by measuring serum urea, creatinine, and kidney injury molecule-1 (KIM-1). Oxidative damage and renal antioxidant levels were also assessed. Additionally, the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), renal cytokine tumor necrosis factor-α (TNF-α), and histopathological changes were evaluated. Results DCF caused a significant increase in serum urea, creatinine, KIM-1, TNF-α, NF-κB, and malondialdehyde levels compared to the control group. However, in the groups treated with DCF plus vitamin E, a significant reduction (P<0.05) in the levels of pro-inflammatory cytokines and malondialdehyde was observed, along with improvement in renal function indices, superoxide dismutase, catalase, and glutathione peroxidase levels comparable to the control group. The observed renal histopathological changes were consistent with the results of the biochemical parameters between the treated groups and the normal control rats. Conclusion Findings from this investigation suggested that DCF can be nephrotoxic at a certain dose when used for a prolonged duration. Co-administration of vitamin E suppressed the elevated inflammatory cytokines and led to changes in the cell redox-sensitive signaling pathways induced by DCF, with eventual amelioration of the nephrotoxicity.
PubMed: 38222238
DOI: 10.7759/cureus.50474 -
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 -
Stem Cell Research & Therapy Nov 2023In regenerative medicine, especially skin tissue engineering, the focus is on enhancing the quality of wound healing. Also, several constructs with different...
Synergistic effect of chitosan-alginate composite hydrogel enriched with ascorbic acid and alpha-tocopherol under hypoxic conditions on the behavior of mesenchymal stem cells for wound healing.
BACKGROUND
In regenerative medicine, especially skin tissue engineering, the focus is on enhancing the quality of wound healing. Also, several constructs with different regeneration potentials have been used for skin tissue engineering. In this study, the regenerative properties of chitosan-alginate composite hydrogels in skin wound healing under normoxic and hypoxic conditions were investigated in vitro.
METHODS
The ionic gelation method was used to prepare chitosan/alginate (CA) hydrogel containing CA microparticles and bioactive agents [ascorbic acid (AA) and α-tocopherol (TP)]. After preparing composite hydrogels loaded with AA and TP, the physicochemical properties such as porosity, pore size, swelling, weight loss, wettability, drug release, and functional groups were analyzed. Also, the hemo-biocompatibility of composite hydrogels was evaluated by a hemolysis test. Then, the rat bone marrow mesenchymal stem cells (rMSCs) were seeded onto the hydrogels after characterization by flow cytometry. The survival rate was analyzed using MTT assay test. The hydrogels were also investigated by DAPI and H&E staining to monitor cell proliferation and viability. To induce hypoxia, the cells were exposed to CoCl. To evaluate the regenerative potential of rMSCs cultured on CA/AA/TP hydrogels under hypoxic conditions, the expression of the main genes involved in the healing of skin wounds, including HIF-1α, VEGF-A, and TGF-β1, was investigated by real-time PCR.
RESULTS
The results demonstrated that the prepared composite hydrogels were highly porous, with interconnected pores that ranged in sizes from 20 to 188 μm. The evaluation of weight loss showed that the prepared hydrogels have the ability to biodegrade according to the goals of wound healing. The reduction percentage of CA/AA/TP mass in 21 days was reported as 21.09 ± 0.52%. Also, based on wettability and hemolysis tests of the CA/AA/TP, hydrophilicity (θ = 55.6° and 53.7°) and hemocompatibility with a hemolysis ratio of 1.36 ± 0.19 were evident for them. Besides, MTT assay, DAPI, and H&E staining also showed that the prepared hydrogels provide a suitable substrate for cell growth and proliferation. Finally, based on real-time PCR, increased expression levels of VEGF and TGF-β1 were observed in rMSCs in hypoxic conditions cultured on the prepared hydrogels.
CONCLUSIONS
In conclusion, this study provides evidence that 3D CA/AA/TP composite hydrogels seeded by rMSCs in hypoxic conditions have great potential to improve wound healing.
Topics: Rats; Animals; Hydrogels; Chitosan; alpha-Tocopherol; Transforming Growth Factor beta1; Alginates; Hemolysis; Wound Healing; Hypoxia; Mesenchymal Stem Cells; Weight Loss
PubMed: 37953287
DOI: 10.1186/s13287-023-03567-2 -
Nutrition Research Reviews Dec 2023Vitamin E is an important nutrient from the earliest stages of life. It plays key roles as an antioxidant and in the maintenance of the immune system, among others.... (Review)
Review
Vitamin E is an important nutrient from the earliest stages of life. It plays key roles as an antioxidant and in the maintenance of the immune system, among others. Vitamin E deficiency (VED), which occurs more frequently in children, is rarely addressed in the literature. This narrative review aims to summarise the chemistry, biology, serum indicators and clinical trials that have evaluated the impact of fortification and other relevant aspects of vitamin E, in addition to the prevalence of its deficiency, in children worldwide. Vitamin E intake in recommended amounts is essential for this nutrient to perform its functions in the body. Serum α-tocopherol is the most widely used biochemical indicator to assess the prevalence of VED. VED has been associated with symptoms secondary to fat malabsorption and may lead to peripheral neuropathy and increased erythrocyte haemolysis. Reduced concentrations of α-tocopherol may be caused by the combination of diets with low amounts of vitamin E and inadequate consumption of fats, proteins and calories. The lowest prevalence of VED was found in Asia and the highest in North America and Brazil. High proportions of VED provide evidence that this nutritional deficiency is a public health problem in children and still little addressed in the international scientific literature. The planning, evaluation and implementation of health policies aimed at combatting VED in the paediatric population are extremely important.
Topics: Child; Humans; alpha-Tocopherol; Food, Fortified; Malnutrition; Vitamin E Deficiency; Nutritional Status
PubMed: 35929460
DOI: 10.1017/S0954422422000142 -
Cureus Apr 2024Alzheimer's disease (AD) is the most common neurodegenerative condition and a form of dementia encountered in medical practice. Despite many proposed and attempted... (Review)
Review
Alzheimer's disease (AD) is the most common neurodegenerative condition and a form of dementia encountered in medical practice. Despite many proposed and attempted treatments, this disease remains a major puzzle in the public health systems worldwide. The initial part of this article provides an overview and illustration of the primary mechanisms responsible for neuronal damage in AD. Subsequently, it offers a critical evaluation of the most noteworthy studies on pharmacological therapy for AD and outlines recent advancements and novel approaches to managing this condition. Main properties, categorization, Food and Drug Administration (FDA) status, mechanisms of action, benefits, and common side effects of the classical and the most recently proposed pharmacological treatments for AD are described. The conventional pharmacological agents revised comprise cholinesterase inhibitors, monoclonal antibodies, and other therapies, such as memantine, valproic acid, and rosiglitazone. The innovative reviewed pharmacological agents comprise the monoclonal antibodies: donanemab, gantenerumab, solanezumab, bapineuzumab, crenezumab, and semorinemab. Nutritional supplements such as alpha-tocopherol (vitamin E) and caprylidene are also revised. Tau and amyloid-targeting treatments include methylthioninium moiety (MT), leuco-methylthioninium bis (LMTM), an oxidized form of MT, and tramiprosate, which inhibits the beta-amyloid (Aβ) monomer aggregation into toxic oligomers. Antidiabetic and anti-neuroinflammation drugs recently proposed for AD treatment are discussed. The antidiabetic drugs include NE3107, an anti-inflammatory and insulin sensitizer, and the diabetes mainstream drug metformin. The anti-neuroinflammatory AD therapies include the use of sodium oligomannate (GV-971), infusions with intravenous immunoglobulin aiming to decrease plasma levels of the constituents of Aβ plaques, and masitinib, a tyrosine kinase inhibitor that impacts mast and microglia cells. Additional anti-inflammatory agents being currently tested in phase-2 clinical trials, such as atomoxetine (selective norepinephrine reuptake inhibitor), losartan (angiotensin 2 receptor agonist), genistein (anti-inflammatory isoflavone neuroprotective agent), trans-resveratrol (polyphenol antioxidant plant estrogen), and benfotiamine (synthetic thiamine precursor), were reviewed. Lastly, drugs targeting Alzheimer's-associated symptoms, such as brexpiprazole (serotonin dopamine activity modulator) and suvorexant (orexin receptor antagonist), respectively, used for agitation and insomnia in AD patients, are reviewed. As experimental investigations and clinical research progress, there is a possibility that a combination of newly tested medications and traditional ones may emerge as a promising treatment option for AD in the future.
PubMed: 38756263
DOI: 10.7759/cureus.58416 -
Pharmaceutics May 2024The microencapsulation of α-tocopherol based on the complex coacervation of low-molecular-weight chitosan (LMWC) and sodium lauryl ether sulphate (SLES) without harmful...
The microencapsulation of α-tocopherol based on the complex coacervation of low-molecular-weight chitosan (LMWC) and sodium lauryl ether sulphate (SLES) without harmful crosslinkers can provide biocompatible carriers that protect it from photodegradation and air oxidation. In this study, the influence of the microcapsule wall composition on carrier performance, compatibility with a high-water-content vehicle for topical application, and release of α-tocopherol were investigated. Although the absence of aldehyde crosslinkers decreased the encapsulation efficiency of α-tocopherol (~70%), the variation in the LMWC/SLES mass ratio (2:1 or 1:1) had no significant effect on the moisture content and microcapsule size. The prepared microcapsule-loaded carbomer hydrogels were soft semisolids with pseudoplastic flow behavior. The integrity of microcapsules embedded in the hydrogel was confirmed by light microscopy. The microcapsules reduced the pH, apparent viscosity, and hysteresis area of the hydrogels, while increasing their spreading ability on a flat inert surface and dispersion rate in artificial sweat. The in vitro release of α-tocopherol from crosslinker-free microcapsule-loaded hydrogels was diffusion-controlled. The release profile was influenced by the LMWC/SLES mass ratio, apparent viscosity, type of synthetic membrane, and acceptor medium composition. Better data quality for the model-independent analysis was achieved when a cellulose nitrate membrane and ethyl alcohol 60% as acceptor medium were used.
PubMed: 38794290
DOI: 10.3390/pharmaceutics16050628 -
International Journal of Chronic... 2023Vitamins and carotenoids are essential in preventing and treating chronic obstructive pulmonary disease (COPD). This study investigated the associations between serum...
PURPOSE
Vitamins and carotenoids are essential in preventing and treating chronic obstructive pulmonary disease (COPD). This study investigated the associations between serum vitamins, carotenoids, and COPD in adults aged ≥ 40 years in the United States.
METHODS
We selected 3487 participants aged ≥40 from the NHANES (2017-2018) and used demographic analysis, sensitivity tests, and different weighted multivariate regression models to investigate the relationship between serum vitamins, carotenoids, and COPD.
RESULTS
Subjects in the highest tertile of serum vitamin C, vitamin E (α-tocopherol), α-carotene, trans-β-carotene, and cis-β-carotene had a 50%, 35%, 51%, 54%, and 51% lower risk of COPD than those in the lowest tertile (P for trend: P=0.0005, <0.0001, 0.0054, 0.0066, and 0.0049). Unfortunately, no significant correlation was found for serum vitamin D levels.
CONCLUSION
Our analysis of nationally representative data from 3487 participants showed that serum levels of vitamin C, vitamin E (α-tocopherol), α-carotene, and β-carotene were negatively associated with the incidence of COPD in adults over 40 years of age in the US The findings highlighted the importance of antioxidant vitamins and carotenoids in respiratory health, while the data showed no significant correlation between vitamin D (25-OHD) and the incidence of COPD.
Topics: Adult; Humans; United States; Middle Aged; beta Carotene; alpha-Tocopherol; Pulmonary Disease, Chronic Obstructive; Nutrition Surveys; Carotenoids; Antioxidants; Vitamins; Vitamin E; Vitamin A; Ascorbic Acid; Vitamin D
PubMed: 38107596
DOI: 10.2147/COPD.S432995 -
Environmental Toxicology and... Aug 2023We investigated the effects of α-tocopherol on oxidative stress-caused damage caused by copper II oxide nanoparticles (CuO NPs) on Oncorhynchus mykiss gonadal cells...
α-tocopherol ameliorates copper II oxide nanoparticles-induced cytotoxic, biochemical, apoptotic, and genotoxic damages in the rainbow trout gonad cells-2 (RTG-2) culture.
We investigated the effects of α-tocopherol on oxidative stress-caused damage caused by copper II oxide nanoparticles (CuO NPs) on Oncorhynchus mykiss gonadal cells (RTG-2) for 24 and 48 h. α-Tocopherol reversed the cell death and alterations in the expressions of genes such as sod1, gpx1a, gpx4b, and igf2 caused by CuO NPs; it also supported the expressions of cat, igf1, and gapdh genes caused by CuO NPs for 24 h and promoted alterations in the expressions of the sod2, gh1, and igf1 genes for 48 h. Additionally, α-tocopherol reversed the caspase 3/7 activity increased by CuO NPs for 24 h and supported it's decrease for 48 h. α-Tocopherol supported the increase in tail DNA (%) affected by CuO NPs for 24 h and reversed it for 48 h. Therefore, α-tocopherol may have the potential to protect against cellular alterations induced by CuO NPs in a time-dependent manner.
Topics: Animals; Copper; Oncorhynchus mykiss; alpha-Tocopherol; Nanoparticles; Oxidative Stress; DNA Damage; Oxides; Metal Nanoparticles
PubMed: 37295739
DOI: 10.1016/j.etap.2023.104168