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Molecules (Basel, Switzerland) Apr 2023Microglia, the resident macrophage-like population in the central nervous system, play a crucial role in the pathogenesis of many neurodegenerative disorders by...
Microglia, the resident macrophage-like population in the central nervous system, play a crucial role in the pathogenesis of many neurodegenerative disorders by triggering an inflammatory response that leads to neuronal death. Neuroprotective compounds to treat or prevent neurodegenerative diseases are a new field of study in modern medicine. Microglia are activated in response to inflammatory stimuli. The pathogenesis of various neurodegenerative diseases is closely related to the constant activation of microglia due to their fundamental role as a mediator of inflammation in the brain environment. α-Tocopherol, also known as vitamin E, is reported to possess potent neuroprotective effects. The goal of this study was to investigate the biological effects of vitamin E on BV2 microglial cells, as a possible neuroprotective and anti-inflammatory agent, following stimulation with lipopolysaccharide (LPS). The results showed that the pre-incubation of microglia with α-tocopherol can guarantee neuroprotective effects during microglial activation induced by LPS. α-Tocopherol preserved the branched morphology typical of microglia in a physiological state. It also reduced the migratory capacity; the production of pro-inflammatory and anti-inflammatory cytokines such as TNF-α and IL-10; and the activation of receptors such as TRL4 and CD40, which modulate the PI3K-Akt signaling pathway. The results of this study require further insights and research, but they present new scenarios for the application of vitamin E as an antioxidant for the purpose of greater neuroprotection in vivo for the prevention of possible neurodegenerative diseases.
Topics: Humans; Lipopolysaccharides; Microglia; alpha-Tocopherol; Neuroprotective Agents; Phosphatidylinositol 3-Kinases; Macrophages; Anti-Inflammatory Agents; Vitamin E; Neurodegenerative Diseases; Nitric Oxide; NF-kappa B
PubMed: 37110573
DOI: 10.3390/molecules28083340 -
Frontiers in Nutrition 2023Spermatogonial stem cells (SSCs) are essential for maintaining reproductive function in males. -lymphoma Mo-MLV insertion region 1 (BMI1) is a vital transcription...
PURPOSE
Spermatogonial stem cells (SSCs) are essential for maintaining reproductive function in males. -lymphoma Mo-MLV insertion region 1 (BMI1) is a vital transcription repressor that regulates cell proliferation and differentiation. However, little is known about the role of BMI1 in mediating the fate of mammalian SSCs and in male reproduction. This study investigated whether BMI1 is essential for male reproduction and the role of alpha-tocopherol (α-tocopherol), a protective agent for male fertility, as a modulator of BMI1 both and .
METHODS
Methyl thiazolyl tetrazolium (MTT) and 5-ethynyl-2'-deoxyuridine (EDU) assays were used to assess the effect of BMI1 on the proliferative ability of the mouse SSC line C18-4. Real-time polymerase chain reaction (PCR), western blotting, and immunofluorescence were applied to investigate changes in the mRNA and protein expression levels of BMI1. Male mice were used to investigate the effect of α-tocopherol and a BMI1 inhibitor on reproduction-associated functionality .
RESULTS
Analysis revealed that BMI1 was expressed at high levels in testicular tissues and spermatogonia in mice. The silencing of BMI1 inhibited the proliferation of SSCs and DNA synthesis and enhanced the levels of γ-H2AX. α-tocopherol enhanced the proliferation and DNA synthesis of C18-4 cells, and increased the levels of BMI1. Notably, α-tocopherol rescued the inhibition of cell proliferation and DNA damage in C18-4 cells caused by the silencing of BMI1. Furthermore, α-tocopherol restored sperm count (Ctrl vs. PTC-209, = 0.0034; Ctrl vs. PTC-209 + α-tocopherol, = 0.7293) and normalized sperm malformation such as broken heads, irregular heads, lost and curled tails , as demonstrated by its antagonism with the BMI1 inhibitor PTC-209.
CONCLUSION
Analysis demonstrated that α-tocopherol is a potent and modulator of BMI1, a transcription factor that plays an important role in in SSC proliferation and spermatogenesis. Our findings identify a new target and strategy for treating male infertility that deserves further pre-clinical investigation.
PubMed: 37139440
DOI: 10.3389/fnut.2023.1141964 -
Antioxidants (Basel, Switzerland) May 2022Vitamin E (alpha-tocopherol) is an essential micronutrient and fat-soluble antioxidant with proposed role in protecting tissues from uncontrolled lipid peroxidation.... (Review)
Review
Vitamin E (alpha-tocopherol) is an essential micronutrient and fat-soluble antioxidant with proposed role in protecting tissues from uncontrolled lipid peroxidation. This vitamin has also important protein function and gene modulation effects. The metabolism of vitamin E depends on hepatic binding proteins that selectively retain food alpha-tocopherol for incorporation into nascent VLDL and tissue distribution together with esterified cholesterol and triglycerides. Chronic kidney disease (CKD) is a condition of oxidative stress and increased lipid peroxidation, that are associated with alterations of alpha-tocopherol metabolism and function. Specific changes have been reported for the levels of its enzymatic metabolites, including both short-chain and long-chain metabolites, the latter being endowed with regulatory functions on enzymatic and gene expression processes important for the metabolism of lipids and xenobiotics detoxification, as well as for the control of immune and inflammatory processes. Vitamin E therapy has been investigated in CKD using both oral vitamin E protocols and vitamin E-coated hemodialyzers, showing promising results in the secondary prevention of cardiovascular disease, as well as of immune and hematological complications. These therapeutic approaches are reviewed in the present article, together with a narrative excursus on the main findings indicating CKD as a condition of relative deficiency and impaired metabolism of vitamin E.
PubMed: 35624853
DOI: 10.3390/antiox11050989 -
World Journal of Nephrology May 2022Kidney disease (KD) is characterized by the presence of elevated oxidative stress, and this is postulated as contributing to the high cardiovascular morbidity and... (Review)
Review
Kidney disease (KD) is characterized by the presence of elevated oxidative stress, and this is postulated as contributing to the high cardiovascular morbidity and mortality in these individuals. Chronic KD (CKD) is related to high grade inflammatory condition and pro-oxidative state that aggravates the progression of the disease by damaging primary podocytes. Liposoluble vitamins (vitamin A and E) are potent dietary antioxidants that have also anti-inflammatory and antiapoptotic functions. Vitamin deficits in CKD patients are a common issue, and multiple causes are related to them: Anorexia, dietary restrictions, food cooking methods, dialysis losses, gastrointestinal malabsorption, The potential benefit of retinoic acid (RA) and α-tocopherol have been described in animal models and in some human clinical trials. This review provides an overview of RA and α tocopherol in KD.
PubMed: 35733655
DOI: 10.5527/wjn.v11.i3.96 -
Scientific Reports May 2024The causal association between vitamin E status and osteoarthritis (OA) remains controversial in previous epidemiological studies. We employed a Mendelian randomization...
The causal association between vitamin E status and osteoarthritis (OA) remains controversial in previous epidemiological studies. We employed a Mendelian randomization (MR) analysis to explore the causal relationship between circulating alpha-tocopherol levels (main forms of vitamin E in our body) and OA. The instrumental variables (IVs) of circulating alpha-tocopherol levels were obtained from a Genome-wide association study (GWAS) dataset of 7781 individuals of European descent. The outcome of OA was derived from the UK biobank. Two-sample MR analysis was used to estimate the causal relationship between circulating alpha-tocopherol levels and OA. The inverse-variance weighted (IVW) method was the primary analysis in this analysis. We used the MR-Egger method to determine horizontal pleiotropic in this work. The heterogeneity effect of instrumental IVs was detected by MR-Egger and IVW analyses. Sensitivity analysis was performed by removing single nucleotide polymorphism (SNP) one by one. Three SNPs (rs964184, rs2108622, and rs11057830) (P < 5E-8) strongly associated with circulating alpha-tocopherol levels were used in this analysis. The IVW-random effect indicated no causal relationship between circulating alpha-tocopherol levels and clinically diagnosed OA (OR = 0.880, 95% CI 0.626, 1.236, P = 0.461). Similarly, IVW analysis showed no causal association between circulating alpha-tocopherol levels and self-reported OA (OR = 0.980, 95% CI 0.954, 1.006, P = 0.139). Other methods of MR analyses and sensitivity analyses revealed consistent findings. MR-Egger and IVW methods indicated no significant heterogeneity between IVs. The MR-Egger intercept showed no horizontal pleiotropic. The results of this linear Mendelian randomization study indicate no causal association between genetically predicted alpha-tocopherol levels and the progression of OA. Alpha-tocopherol may not provide beneficial and more favorable outcomes for the progression of OA. Further MR analysis based on updated GWASs with more IVs is required to verify the results of our study.
Topics: Humans; alpha-Tocopherol; Mendelian Randomization Analysis; Osteoarthritis; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Male; Female; Genetic Predisposition to Disease
PubMed: 38698019
DOI: 10.1038/s41598-024-60676-5 -
Brain Sciences Jul 2023Dietary constituents may affect the progression of Parkinson's disease (PD). This study aimed to assess the contribution of dietary intake of vitamins and minerals to...
BACKGROUND AND OBJECTIVE
Dietary constituents may affect the progression of Parkinson's disease (PD). This study aimed to assess the contribution of dietary intake of vitamins and minerals to the severity, motor and non-motor symptoms, and risk of PD.
METHODS
In this case-control study, 120 patients with PD and 50 healthy participants participated. Dietary intake of vitamins and minerals was determined using a 147-item food frequency questionnaire. The severity of PD was determined by the Unified Parkinson's Disease Rating Scale (UPDRS).
RESULTS
Patients with PD had lower intake of several vitamins and minerals including lycopene, thiamine, vitamin B6, vitamin B12, pantothenic acid, magnesium, zinc, manganese, selenium, chromium, and phosphorus, but had higher intake of α-tocopherol. High dietary intake of vitamin A, α-carotene, β-cryptoxanthin, vitamin C, and α-tocopherol were correlated with increased odds of PD. High intake of lycopene, thiamin, vitamin B6, pantothenic acid, magnesium, zinc, manganese, chromium, and phosphorous correlated with reduced odds of PD. The predictive power of α-tocopherol concerning the risk of PD was stronger relative to other vitamins. Dietary intake of pantothenic acid was negatively correlated with PD severity and symptoms of motor examination and complication. The severity and motor symptoms of PD were also negatively correlated with β-carotene, vitamin C, riboflavin, vitamin B6, and biotin intake. The UPDRS total score and motor symptoms in PD patients were negatively correlated with phosphorus, magnesium, zinc, manganese, and chromium, and strongly with potassium intake.
CONCLUSION
The findings indicate that adequate dietary intake of vitamins and minerals may have a preventive effect on developing PD and progression of motor decline.
PubMed: 37509049
DOI: 10.3390/brainsci13071119 -
Veterinary Medicine International 20222,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent organic pollutant that induces overproduction of reactive oxygen species (ROS). Studies on avoiding the...
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent organic pollutant that induces overproduction of reactive oxygen species (ROS). Studies on avoiding the adverse effects of dioxin pollution exposure are needed in all aspects, including reproductive health. This study aimed to determine the effect of -tocopherol on superoxide dismutase (SOD) and malondialdehyde (MDA) levels, live spermatozoa, apoptosis, and necrosis in male rats exposed to dioxin as a model. Thirty healthy 12-week-old male rats were randomly divided into five groups. Rats in the control group were given corn oil twice daily at 4-hour intervals. The remaining rats were given TCDD 700 mg/kg BW daily, followed by administration of corn oil and -tocopherol at doses of 77, 140, and 259 mg/kg BW/d for T0, T1, T2, and T3 groups, respectively. The treatments were conducted for 45 days; all rats were euthanized to collect blood and testicular samples on day 46. The results showed that exposure of TCDD resulted in a decrease in SOD activity and live spermatozoa and increased MDA level and death, apoptosis, and necrosis of spermatozoa (T0) compared to the control (C) group ( < 0.05). The administration of -tocopherol, starting from the doses of 77 (T1), 149 (T2), and 259 mg (T3) per kg BW, was sequentially followed by returning MDA levels, recovering SOD activities, and restoration in the percentage of living, dead, apoptotic, and necrotic spermatozoa, similar ( > 0.05) to those of the control group. It could be concluded that the administration of -tocopherol resolves the harmful effects of TCDD on the viability of spermatozoa in rats as a model.
PubMed: 35237404
DOI: 10.1155/2022/3685686 -
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 -
Antioxidants (Basel, Switzerland) Feb 2023Targeted drugs have been used to treat mitochondrial dysfunction-related diseases, including metabolic disorders and cancer; however, targeting and penetrating...
Targeted drugs have been used to treat mitochondrial dysfunction-related diseases, including metabolic disorders and cancer; however, targeting and penetrating intracellular organelles remains a challenge. Dominant targeting approaches for therapeutic delivery are detailed in many nanoemulsion studies and show the tremendous potential of targeted delivery to inhibit cancer cell growth. Dequalinium (DQA) and α-tocopherol succinate (α-TOS) are good agents for targeting mitochondria. In this study, we aimed to develop a mitochondria-targeting emulsion, using DQA and α-TOS (DTOS), for cancer treatment. DTOS emulsions of 150-170 nm in diameter were formulated using homogenization. DQA and α-TOS were used as bifunctional agents (surfactants) to stabilize the nanoemulsion and anticancer drugs. Various molar ratios of DQA and α-TOS were tested to determine the optimal condition, and DTOS 5-5 was selected for further study. The DTOS emulsion showed improved stability, as evidenced by its ability to remain stable for three years at room temperature. This stability, combined with its effective targeting of mitochondria, led to inhibition of 71.5% of HeLa cells after 24 h. The DTOS emulsion effectively inhibited spheroid growth in the 3D model, as well as prevented the growth of HeLa cells grafted onto zebrafish larvae. These results highlight the DTOS emulsion's promising potential for mitochondria-targeting and cancer treatment.
PubMed: 36829996
DOI: 10.3390/antiox12020437 -
Turkish Neurosurgery 2021To evaluate the functional and histopathological results of alpha-tocopherol (vitamin E) and vitamin B12 on an experimental rat model of peripheral nerve injury.
AIM
To evaluate the functional and histopathological results of alpha-tocopherol (vitamin E) and vitamin B12 on an experimental rat model of peripheral nerve injury.
MATERIAL AND METHODS
This research included 32 Wistar Hannover rats. The sciatic nerves of the animals were crushed using an aneurysm clamp. The rats were divided into 4 groups, as group 0 (the controls; no treatment), and groups B12, E, and B12+E, respectively. The rats were analyzed functionally, using the sciatic functional index (SFI), and histopathologically.
RESULTS
In the functional analysis, it was determined that vitamin E was as influential as B12. Concomitant use of these 2 vitamins was found to be more beneficial. The SFI was significantly higher in the B12+E group when compared with that of the B12 group, which indicated that vitamin E improved the healing effects of vitamin B12. In the histopathological evaluation, vitamin E was not effective in the treatment of axonal degeneration (AxD) or edema/inflammation (EI) by itself. Although vitamin B12 was effective in the treatment of EI, it was ineffective in the treatment of AxD. However, the combination of these vitamins decreased both AxD and EI, which showed that the additive effects of these vitamins could reverse neurological injury when used together.
CONCLUSION
Vitamins B12 and E were effective in the functional recovery of peripheral nerve injury (PNI). Neither vitamin B12 nor E was effective in the treatment AxD; however, their combination was effective in the treatment of AxD. The results suggested that vitamin E was effective in the treatment of PNI, especially when combined with vitamin B12. It is our belief that the combination of these vitamins could be used in the treatment of PNI, especially after future studies have been conducted on humans.
Topics: Animals; Antioxidants; Drug Therapy, Combination; Male; Peripheral Nerve Injuries; Rats; Rats, Wistar; Recovery of Function; Sciatic Nerve; Vitamin B 12; Vitamin B Complex; alpha-Tocopherol
PubMed: 33575997
DOI: 10.5137/1019-5149.JTN.30784-20.3