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1.
Biomolecules ; 13(1)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36671529

RESUMO

Vitamin C (ascorbic acid; AA) and copper (Cu2+) are well used supplements with many health-promoting actions. However, when they are used in combination, the Fenton reaction occurs, leading to the formation of highly reactive hydroxyl radicals. Given that kidney is vulnerable to many toxicants including free radicals, we speculated that the in vivo administration of AA plus Cu2+ may cause oxidative kidney injury. The purpose of this study was to address this possibility. Mice were administered with AA and Cu2+, alone or in combination, via oral gavage once a day for various periods. Changes in the systemic oxidative status, as well renal structure and functions, were examined. The administration of AA plus Cu2+ elevated protein oxidation in serum, intestine, bladder, and kidney, as evidenced by the increased sulfenic acid formation and decreased level of free sulfhydryl groups (-SH). The systemic oxidative stress induced by AA plus Cu2+ was associated with a significant loss of renal function and structure, as indicated by the increased blood urea nitrogen (BUN), creatinine and urinary proteins, as well as glomerular and tubular cell injury. These effects of AA and Cu2+ were only observed when used in combination, and could be entirely prevented by thiol antioxidant NAC. Further analysis using cultured renal tubular epithelial cells revealed that AA plus Cu2+ caused cellular protein oxidation and cell death, which could be abolished by NAC and catalase. Moreover, coincubation of AA and Cu2+ led to H2O2 production. Collectively, our study revealed that a combined administration of AA and Cu2+ resulted in systemic oxidative stress and renal cell injury. As health-promoting supplements, AA and Cu2+ should not be used together.


Assuntos
Ácido Ascórbico , Cobre , Camundongos , Animais , Ácido Ascórbico/farmacologia , Ácido Ascórbico/metabolismo , Cobre/metabolismo , Peróxido de Hidrogênio/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Estresse Oxidativo , Vitaminas/farmacologia , Rim/metabolismo
2.
Biomed Res Int ; 2023: 4371611, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36704721

RESUMO

One of the most often utilized nanoparticles (NPs) in several technologies is zinc oxide (ZnO) NPs. However, these NPs are said to have harmful effects on the reproductive system. Thus, we designed this study to specify the potential preventive activity of vitamins (Vits) A, C, and E, as antioxidants, against toxicity of ZnO NPs in the testes of rats. A total of 54 Wistar rats were arranged in 9 groups of 6 and then orally received water (control 1), olive oil (control 2), Vit A (1000 IU/kg), Vit C (200 mg/kg), Vit E (100 IU/kg), ZnO (200 mg/kg), ZnO+Vit A, ZnO+Vit C, and ZnO+Vit E. To determine the amount of testicular injury, sperm analysis and histological evaluation were performed. In addition, oxidative stress status was examined using colorimetric and qRT-PCR methods. Our findings suggest that ZnO NPs cause adverse effects on sperm parameters and testicular histology. Furthermore, oxidative biomarkers (malondialdehyde and total oxidant capacity) were enhanced in the ZnO group. By contrast, the gene expression and activities of antioxidant enzymes (SOD, GPx, and CAT) noted a remarkable decrease in the ZnO group regarding control (p < 0.05). However, oxidative markers were remarkably mitigated after combined treatment of ZnO NPs and Vits A, C, or E compared to the rats given ZnO NPs (p < 0.05). Additionally, compared to the ZnO NP group, the rats receiving Vits+ZnO NPs exhibit increased antioxidant enzyme activity and mRNA expression (p < 0.05). The findings demonstrate the abovementioned Vits' ameliorative effects on toxicity incurred by ZnO NPs.


Assuntos
Nanopartículas , Estresse Oxidativo , Óxido de Zinco , Animais , Masculino , Ratos , Antioxidantes/metabolismo , Nanopartículas/toxicidade , Ratos Wistar , Sêmen/metabolismo , Espermatozoides/metabolismo , Testículo/metabolismo , Vitamina A/farmacologia , Vitaminas/farmacologia , Óxido de Zinco/toxicidade
3.
Vitam Horm ; 121: 293-318, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36707138

RESUMO

Although several recent studies have shown that vitamin D supplementation beneficially decreases oxidative stress parameters, there is no consensus on this subject in humans. Thus the role of vitamin D supplementation has recently become a controversial topic because large intervention studies in humans have not shown significant benefits. These studies have indicated that supplementation with precursor forms of active vitamin D has no effect on all-cause mortality, cannot reduce the fracture risk of the elderly, cannot reduce the incidence of cancer or cardiovascular disease in the elderly, and cannot significantly reduce the incidence risk of diabetes in the elderly. However, a link between several age-related diseases and enhanced oxidative stress has been found in mice with insufficient or deficient 1,25-dihydroxyvitamin D (1,25(OH)2D), the active form of vitamin D, which indicates that reduced active vitamin D accelerates aging and age-related diseases by increasing oxidative stress. Furthermore, supplementation of exogenous 1,25(OH)2D3, or antioxidants, could dramatically postpone aging, prevent osteoporosis and spontaneous tumor development induced by 1,25(OH)2D insufficiency or deficiency, by inhibiting oxidative stress. Mechanistically, the antioxidative effects of 1,25(OH)2D3 are carried out via the vitamin D receptor (VDR) by activation of the Nrf2 oxidative stress response pathway though transcriptional or posttranscriptional activation of Nrf2 or transcriptional upregulation of Sirt1 and Bmi1 expression. Whether discrepancies between studies in humans and in mice reflect the different forms of vitamin D examined remains to be determined.


Assuntos
Fator 2 Relacionado a NF-E2 , Vitamina D , Humanos , Camundongos , Animais , Idoso , Vitamina D/farmacologia , Vitamina D/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/farmacologia , Vitaminas/farmacologia , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Estresse Oxidativo , Envelhecimento , Antioxidantes/farmacologia
4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(1): 7-13, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36647636

RESUMO

Keeping the immune system healthy forms an effective way to fight infections. Past experience has shown that, in addition to effective interventions including vaccination, drug therapy, and non-pharmaceutical intervention (NPI), dietary nutrition and mental health are also key factors in maintaining immune system health and combating emerging and sudden outbreaks of infections. As the main dietary nutrients, vitamins are active regulators of the immune response and exert a critical impact on the immunity of the human body. Vitamin deficiency causes increased levels of inflammation and decreased immunity, which usually starts in the oral tissues. Appropriate vitamin supplementation can help the body optimize immune function, enhance oral immunity, and reduce the negative impact of pathogen infection on the human body, which makes it a feasible, effective, and universally applicable anti-infection solution. This review focuses on the immunomodulatory effects of vitamin A, B, C, D, and E and proposes that an omics-based new systemic approach will lead to a breakthrough of the limitations in traditional single-factor single-pathway research and provide the direction for the basic and applied research of vitamin immune regulation and anti-infection in all aspects.


Assuntos
Vitamina A , Vitaminas , Humanos , Vitaminas/uso terapêutico , Vitaminas/farmacologia , Vitamina A/farmacologia , Sistema Imunitário/fisiologia , Vitamina K/farmacologia , Inflamação/tratamento farmacológico , Suplementos Nutricionais
5.
J Anim Sci ; 1012023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36566429

RESUMO

The effects of a Nutritional Packet offered to beef steers during the final 64 d of the feedlot-finishing phase on growth performance, carcass characteristics, nutrient digestibility, and feeding behavior were evaluated. Angus-crossbred steers (N = 120; initial body weight = 544 ± 52 kg) were assigned to 30 pens (4 steers per pen; 15 pens per treatment) in a randomized complete block design where pen was the experimental unit. A steam-flaked corn-based finishing diet was offered to ad libitum, and the treatments were as follows: 1) control and 2) 30 g per steer-daily (dry matter basis) of the Nutritional Packet. The Nutritional Packet was formulated to provide 1.7 × 1010 CFU per steer-daily of Saccharomyces cerevisiae, 162 mg per steer-daily of vitamin C; 400 mg per steer-daily of vitamin B1; 2.4 g per steer-daily of NaCl, and 2.4 g per steer-daily of KCl. Data were analyzed using the GLIMMIX procedure of SAS with the fixed effect of treatment and the random effect of block. The average daily gain (P = 0.89), dry matter intake (P = 0.57), and gain efficiency (P = 0.82) were not affected by the inclusion of the Nutritional Packet. Digestibility of dry and organic matter, and neutral and acid detergent fiber increased (P ≤ 0.02) for steers offered the Nutritional Packet, while a trend for the same response was observed for hemicellulose (P = 0.08). The 12th rib backfat thickness increased (P = 0.02) for carcasses of steers offered the Nutritional Packet, followed by a greater (P = 0.03) calculated yield grade, whereas other carcass traits were not affected (P ≥ 0.32). While the steers under the control diet decreased behavior activities on day 63, a consistent pattern of feeding behavior measurements (activity min/d and min/kg of dry and organic matter, fiber fractions, and digestible nutrients) were observed for steers consuming the Nutritional Packet during both feeding behavior assessment periods (treatment × period interactions, P ≤ 0.03). Overall time (min/d) spent on rumination, drinking, active, chewing, and resting were not affected (P ≥ 0.28) by treatments. The Nutritional Packet offered to steers during the final 64 d on feed induced an improvement in apparent digestibility of nutrients and carcass fat deposition, without affecting growth performance or other carcass quality indices. Such effects associated with the more consistent feeding behavior of steers receiving the Nutritional Packet may warrant a shorter time on feed during the final portion of the finishing phase.


Excessive intake of rapidly fermentable nutrients by feedlot cattle can result in clinical or subclinical disorders that impair nutrient digestion, while negatively affecting animal development and health. Incidences of subclinical digestive disturbances may increase during the last days on feed in cattle fed in confinement. Manipulation of diets with probiotics (live yeast), vitamins (C and B1), and electrolytes (NaCl and KCl) to aid subclinical digestive disorders faced by cattle offered high-energy diets was addressed in the current experiment. The use of such nutritional technologies is based on previous reports that these technologies can stabilize ruminal pH, improve nutrient digestibility, enhance rumen microbial growth and energy metabolism, reduce oxidative stress, augment immune function, and prevent vitamin deficiencies induced by energy-dense diets. Therefore, it was important to investigate the effects of a packet containing these technologies during the feedlot final days on feed. When offered to steers during the final 64 d prior to harvest, a Nutritional Packet containing live yeast, vitamins C and B1, and electrolytes improved digestibility of nutrients and carcass fat deposition, while reducing variation in feeding behavior. Such effects may warrant an earlier harvest date when animals receive the packet.


Assuntos
Digestão , Saccharomyces cerevisiae , Bovinos , Animais , Digestão/fisiologia , Ácido Ascórbico/farmacologia , Ração Animal/análise , Dieta/veterinária , Vitaminas/farmacologia , Comportamento Alimentar , Nutrientes , Vapor , Composição Corporal
6.
Eur J Med Res ; 27(1): 295, 2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36528637

RESUMO

BACKGROUND: The inhibitory activities of vitamins K2 against clinical isolates of quinolone-resistant and methicillin-resistant Staphylococcus aureus (QR-MRSA) are unclear. The main aim is to better understand of inhibitory activities of vitamins K2, multi-locus sequence typing (MLST), SCCmec, and spa typing in clinical isolates of QR-MRSA on those mutation and gene expressions. MATERIALS AND METHODS: After collecting S. aureus clinical isolates and detecting QR-MRSA, the genes encoding norA, grlA, grlB, gyrA, and gyrB were sequenced. After treating isolates by vitamin K2, isolates were prepared to measure norA, grlA, grlB, gyrA, and gyrB gene expression. The quantitative-real-time PCR was used to measure the expression of efflux pump genes. RESULTS: QR-MRSA, MDR, and XDR strains were reported in 59.4%, 73.9%, and 37.6% of isolates, respectability. SCCmecIV (36.5%) and SCCmecV (26.8%) had the highest frequency. Thirty-nine spa types were identified, t021, t044, and t267 types most prevalent in QR-MRSA isolates. ST22 and ST30 dominated the invasive, drug-resistant isolates and QR-MRSA. In 24 h incubated isolates, the most noticeable change of gene expression with vitamin K2 was that the norA, gyrA, and grlB genes were highly repressed. However, the down-regulation of grlA at 24 h after being treated by vitamin K2 was more than another gene. Further, a significant decrease was observed in QR-MRSA-treated isolates compared to un-treated isolates. In other words, norA, grlA, grlB, gyrA, and gyrB genes were less suppressed by QR-MRSA (p ≤ 0.01, p ≤ 0.05). CONCLUSION: Vitamin K2 has significant inhibitory effects on the genes responsible for resistance to fluoroquinolone antibiotics. However, a subminimum inhibitory concentration (sub-MIC) level of vitamin K2 was delayed but did not completely inhibit norA, grlA, grlB, gyrA, and gyrB genes in MRSA strains.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Quinolonas , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Tipagem de Sequências Multilocus , Quinolonas/farmacologia , Vitamina K 2/farmacologia , Testes de Sensibilidade Microbiana , Vitaminas/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/genética , Antibacterianos/farmacologia
7.
Nutrients ; 14(24)2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36558407

RESUMO

Vitamin C was reported to be able to protect against oxidative damage due to its reducibility. 120 Wistar rats were randomly divided into 4 × 2 groups, including normal iodine (NI), high iodine (HI), low vitamin C (HI + LC), and high vitamin C (HI + HC); potassium iodide (KI) and potassium iodate (KIO3) were commonly used as additives for iodized salt, so every group was also divided into KI and KIO3 groups. After 6 months' feed, the activities of antioxidant enzymes and Lipid Peroxide (MDA) content in serum, liver, kidney, brain, thyroid and lens were determined. In serum, for males, long-term excess iodine intake caused oxidative damage; in the liver, male rats in the HI + LC group had the highest MDA content, which showed that low-dose vitamin C might promote oxidative damage; in kidneys, the MDA content in the HI and HI + LC groups of females was higher; in the brain, high-dose vitamin C could increase the activity of superoxide dismutase (SOD), which was decreased by high iodine intake, and it also decreased MDA content; in the thyroid, for KIO3, the activity of SOD in the HI group was lower than NI and HI + LC; in the lens, the MDA content in females was lower than males. Long-term excess iodine exposure caused oxidative damage and showed sex difference, and vitamin C had a protective effect on it, especially for high-dose vitamin C.


Assuntos
Ácido Ascórbico , Iodo , Vitaminas , Animais , Feminino , Masculino , Ratos , Antioxidantes/metabolismo , Ácido Ascórbico/farmacologia , Iodo/efeitos adversos , Estresse Oxidativo , Iodeto de Potássio/efeitos adversos , Ratos Wistar , Superóxido Dismutase/metabolismo , Vitaminas/farmacologia
8.
Exp Appl Acarol ; 88(2): 209-224, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36348156

RESUMO

Essential oils of Origanum majorana and Satureja thymbra as well as carvacrol are natural products that are known to have potent antioxidant activities. The current study was designed to investigate the role of the antioxidant properties of these natural products in their acaricidal activities against Rhipicephalus annulatus larvae. The synergistic and/or antagonistic effects of the addition of vitamins E and C and hydrogen peroxide (H2O2) to these natural products were also evaluated. Larval packet tests were used to evaluate the acaricidal activities against the larvae of R. annulatus. The antioxidant effectiveness of these products was determined by a DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging assay. The addition of vitamin E at 100 mg/mL to O. majorana and S. thymbra decreased the concentrations required to achieve the death of half of the larvae (LC50) to 0.44 and 0.47%, respectively. The combination of O. majorana and S. thymbra attained the LC50 at 1.54% which was decreased to 0.69% after addition of vitamin E. Also, the addition of vitamin E to carvacrol reduced the LC50 to 0.27%. The total antioxidant activity of these natural products increased significantly in presence of vitamin E. The addition of H2O2 inhibited the acaricidal activity of all tested materials, especially at low concentrations. All treatments induced an increase in lipid peroxidation, whereas carvacrol-treated larvae revealed the lowest values for the superoxide dismutase. Glutathione peroxidase and catalase activity decreased in larvae treated with S. thymbra combined with vitamin E. In conclusion, the addition of vitamins E and C increased the acaricidal activities of the tested compounds, whereas the addition of H2O2 decreased these activities. The antioxidant activities of essential oils and their active components may play an important role in mediating their acaricidal activities.


Assuntos
Acaricidas , Produtos Biológicos , Óleos Voláteis , Rhipicephalus , Animais , Acaricidas/farmacologia , Acaricidas/química , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Antioxidantes/farmacologia , Peróxido de Hidrogênio/farmacologia , Larva , Vitamina E/farmacologia , Produtos Biológicos/farmacologia , Vitaminas/farmacologia
9.
Cells ; 11(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36359850

RESUMO

The turn-on mutations of the KRAS gene, coding a small GTPase coupling growth factor signaling, are contributing to nearly 25% of all human cancers, leading to highly malignant tumors with poor outcomes. Targeting of oncogenic KRAS remains a most challenging task in oncology. Recently, the specific G12C mutant KRAS inhibitors have been developed but with a limited clinical outcome because they acquire drug resistance. Alternatively, exploiting a metabolic breach of KRAS-mutant cancer cells related to a glucose-dependent sensitivity to oxidative stress is becoming a promising indirect cancer targeting approach. Here, we discuss the use of a vitamin C (VC) acting in high dose as an oxidative "Trojan horse" agent for KRAS-mutant cancer cells that can be potentiated with another oxidizing drug arsenic trioxide (ATO) to obtain a potent and selective cytotoxic impact. Moreover, we outline the advantages of VC's non-natural enantiomer, D-VC, because of its distinctive pharmacokinetics and lower toxicity. Thus, the D-VC and ATO combination shows a promising path to treat KRAS-mutant cancers in clinical settings.


Assuntos
Ácido Ascórbico , Neoplasias , Humanos , Trióxido de Arsênio/farmacologia , Trióxido de Arsênio/uso terapêutico , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Estresse Oxidativo , Vitaminas/farmacologia , Oxirredução , Neoplasias/tratamento farmacológico , Neoplasias/genética
10.
Nutrients ; 14(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36364774

RESUMO

Intensive epigenome and transcriptome analyses have unveiled numerous biological mechanisms, including the regulation of cell differentiation, proliferation, and induced apoptosis in neoplastic cells, as well as the modulation of the antineoplastic action of the immune system, which plausibly explains the observed population-based relationship between low vitamin D status and increased cancer risk. However, large randomized clinical trials involving cholecalciferol supplementation have so far failed to show the potential of such interventions in cancer prevention. In this article, we attempt to reconcile the supposed contradiction of these findings by undertaking a thorough review of the literature, including an assessment of the limitations in the design, conduct, and analysis of the studies conducted thus far. We examine the long-standing dilemma of whether the beneficial effects of vitamin D levels increase significantly above a critical threshold or if the conjecture is valid that an increase in available cholecalciferol translates directly into an increase in calcitriol activity. In addition, we try to shed light on the high interindividual epigenetic and transcriptomic variability in response to cholecalciferol supplementation. Moreover, we critically review the standards of interpretation of the available study results and propose criteria that could allow us to reach sound conclusions in this field. Finally, we advocate for options tailored to individual vitamin D needs, combined with a comprehensive intervention that favors prevention through a healthy environment and responsible health behaviors.


Assuntos
Neoplasias , Vitamina D , Humanos , Vitamina D/uso terapêutico , Suplementos Nutricionais , Vitaminas/farmacologia , Vitaminas/uso terapêutico , Colecalciferol/farmacologia , Colecalciferol/uso terapêutico , Neoplasias/prevenção & controle , Neoplasias/tratamento farmacológico
11.
Nutrients ; 14(21)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36364820

RESUMO

The non-classical role of vitamin D has been investigated in recent decades. One of which is related to its role in skeletal muscle. Satellite cells are skeletal muscle stem cells that play a pivotal role in skeletal muscle growth and regeneration. This systematic review aims to investigate the effect of vitamin D on satellite cells. A systematic search was performed in Scopus, MEDLINE, and Google Scholar. In vivo studies assessing the effect of vitamin D on satellite cells, published in English in the last ten years were included. Thirteen in vivo studies were analyzed in this review. Vitamin D increases the proliferation of satellite cells in the early life period. In acute muscle injury, vitamin D deficiency reduces satellite cells differentiation. However, administering high doses of vitamin D impairs skeletal muscle regeneration. Vitamin D may maintain satellite cell quiescence and prevent spontaneous differentiation in aging. Supplementation of vitamin D ameliorates decreased satellite cells' function in chronic disease. Overall, evidence suggests that vitamin D affects satellite cells' function in maintaining skeletal muscle homeostasis. Further research is needed to determine the most appropriate dose of vitamin D supplementation in a specific condition for the optimum satellite cells' function.


Assuntos
Células Satélites de Músculo Esquelético , Vitamina D/farmacologia , Regeneração , Desenvolvimento Muscular , Fibras Musculares Esqueléticas/fisiologia , Diferenciação Celular/fisiologia , Músculo Esquelético , Vitaminas/farmacologia
12.
Nutrients ; 14(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36364898

RESUMO

Considering the existing controversy over the possible role of acute antioxidant vitamins in reducing exercise-induced muscle damage (EIMD), this doubled-blind, randomized and controlled trial aimed to determine whether supplementation with vitamins C and E could mitigate the EIMD in endurance-trained runners (n = 18). The exercise protocol involved a warm-up followed by 6 to 8 bouts of 1 km running at 75% maximum heart rate (HRmax). Two hours before the exercise protocol, participants took the supplementation with vitamins or placebo, and immediately afterwards, blood lactate, rate of perceived exertion and performance were assessed. At 24 h post-exercise, CK, delayed onset muscle soreness and performance were determined (countermovement jump, squat jump and stiffness test). The elastic index and vertical stiffness were calculated using a stiffness test. Immediately after the exercise protocol, all participants showed improved maximum countermovement jump, which only persisted after 24 h in the vitamin group (p < 0.05). In both groups, squat jump height was significantly greater (p < 0.05) immediately after exercise and returned to baseline values after 24 h. The elastic index increased in the vitamin group (p < 0.05), but not in the placebo group. In both groups, lactate levels increased from pre- to immediately post-exercise (p < 0.05), and CK increased from pre- to 24 h post-exercise (p < 0.05). No significant differences between groups were observed in any of the variables (p > 0.05). Vitamin C and E supplementation does not seem to help with EIMD in endurance-trained individuals.


Assuntos
Músculo Esquelético , Mialgia , Humanos , Mialgia/etiologia , Mialgia/prevenção & controle , Ácido Ascórbico/farmacologia , Vitaminas/farmacologia , Método Duplo-Cego , Vitamina E/farmacologia , Suplementos Nutricionais , Lactatos/farmacologia
13.
Nutrients ; 14(22)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36432424

RESUMO

Vitamin D is a steroid hormone that has been widely studied as a potential therapy for multiple sclerosis and other inflammatory disorders. Pre-clinical studies have implicated vitamin D in the transcription of thousands of genes, but its influence may vary by cell type. A handful of clinical studies have failed to identify an in vivo gene expression signature when using bulk analysis of all peripheral immune cells. We hypothesized that vitamin D's gene signature would vary by immune cell type, requiring the analysis of distinct cell types. Multiple sclerosis patients (n = 18) were given high-dose vitamin D (10,400 IU/day) for six months as part of a prospective clinical trial (NCT01024777). We collected peripheral blood mononuclear cells from participants at baseline and again after six months of treatment. We used flow cytometry to isolate three immune cell types (CD4+ T-cells, CD19+ B-cells, CD14+ monocytes) for RNA microarray analysis and compared the expression profiles between baseline and six months. We identified distinct sets of differentially expressed genes and enriched pathways between baseline and six months for each cell type. Vitamin D's in vivo gene expression profile in the immune system likely differs by cell type. Future clinical studies should consider techniques that allow for a similar cell-type resolution.


Assuntos
Esclerose Múltipla , Vitamina D , Humanos , Leucócitos Mononucleares , Monócitos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/genética , Estudos Prospectivos , Linfócitos T , Transcriptoma , Vitaminas/farmacologia , Vitaminas/uso terapêutico
14.
Int J Mol Sci ; 23(19)2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36232688

RESUMO

Acute myeloid leukemia (AML)-the most frequent form of adult blood cancer-is characterized by heterogeneous mechanisms and disease progression. Developing an effective therapeutic strategy that targets metabolic homeostasis and energy production in immature leukemic cells (blasts) is essential for overcoming relapse and improving the prognosis of AML patients with different subtypes. With respect to metabolic regulation, fructose-1,6-bisphosphatase 1 (FBP1) is a gluconeogenic enzyme that is vital to carbohydrate metabolism, since gluconeogenesis is the central pathway for the production of important metabolites and energy necessary to maintain normal cellular activities. Beyond its catalytic activity, FBP1 inhibits aerobic glycolysis-known as the "Warburg effect"-in cancer cells. Importantly, while downregulation of FBP1 is associated with carcinogenesis in major human organs, restoration of FBP1 in cancer cells promotes apoptosis and prevents disease progression in solid tumors. Recently, our large-scale sequencing analyses revealed FBP1 as a novel inducible therapeutic target among 17,757 vitamin-D-responsive genes in MV4-11 or MOLM-14 blasts in vitro, both of which were derived from AML patients with FLT3 mutations. To investigate FBP1's anti-leukemic function in this study, we generated a new AML cell line through lentiviral overexpression of an FBP1 transgene in vitro (named FBP1-MV4-11). Results showed that FBP1-MV4-11 blasts are more prone to apoptosis than MV4-11 blasts. Mechanistically, FBP1-MV4-11 blasts have significantly increased gene and protein expression of P53, as confirmed by the P53 promoter assay in vitro. However, enhanced cell death and reduced proliferation of FBP1-MV4-11 blasts could be reversed by supplementation with post-glycolytic metabolites in vitro. Additionally, FBP1-MV4-11 blasts were found to have impaired mitochondrial homeostasis through reduced cytochrome c oxidase subunit 2 (COX2 or MT-CO2) and upregulated PTEN-induced kinase (PINK1) expressions. In summary, this is the first in vitro evidence that FBP1-altered carbohydrate metabolism and FBP1-activated P53 can initiate leukemic death by activating mitochondrial reprogramming in AML blasts, supporting the clinical potential of FBP1-based therapies for AML-like cancers.


Assuntos
Metabolismo dos Carboidratos , Células Precursoras de Granulócitos , Leucemia Mieloide Aguda , Mitocôndrias , Proteína Supressora de Tumor p53 , Apoptose , Metabolismo dos Carboidratos/efeitos dos fármacos , Metabolismo dos Carboidratos/genética , Dióxido de Carbono/metabolismo , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Progressão da Doença , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Frutose/farmacologia , Frutose-Bifosfatase/genética , Frutose-Bifosfatase/metabolismo , Glicólise , Células Precursoras de Granulócitos/metabolismo , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Quinases/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Vitamina D/farmacologia , Vitaminas/farmacologia , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/metabolismo
15.
Nutrients ; 14(19)2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36235793

RESUMO

Vitamins are known to generate bitterness, which may contribute to an off-taste or aftertaste for some nutritional supplements. This negative sensation can lead to a reduction in their consumption. Little is known about the bitter taste threshold and taste sensing system for the bitter taste detection of vitamins. To better understand the mechanisms involved in bitterness perception, we combined taste receptor functional assays and sensory analysis. In humans, bitter taste detection is mediated by 25 G-protein-coupled receptors belonging to the TAS2R family. First, we studied the bitterness of thirteen vitamins using a cellular-based functional taste receptor assay. We found four vitamins that can stimulate one or more TAS2Rs. For each positive molecule-receptor combination, we tested seven increasing concentrations to determine the half-maximal effective concentration (EC50) and the cellular bitter taste threshold. Second, we measured the bitter taste detection threshold for four vitamins that exhibit a strong bitter taste using a combination of ascending series and sensory difference tests. A combination of sensory and biological data can provide useful results that explain the perception of vitamin bitterness and its real contribution to the off-taste of nutritional supplements.


Assuntos
Papilas Gustativas , Paladar , Humanos , Receptores Acoplados a Proteínas G , Limiar Gustativo , Vitamina A , Vitaminas/farmacologia
16.
Free Radic Biol Med ; 193(Pt 1): 253-273, 2022 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-36270517

RESUMO

Vitamin D is considered an essential micronutrient for human health that is metabolized into a multifunctional secosteroid hormone. We can synthesize it in the skin through ultraviolet B (UVB) rays or acquire it from the diet. Its deficiency is a major global health problem that affects all ages and ethnic groups. Furthermore, dysregulation of vitamin D homeostasis has been associated with premature aging, driven by various cellular processes, including oxidative stress and cellular senescence. Various studies have shown that vitamin D can attenuate oxidative stress and delay cellular senescence, mainly by inducing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and Klotho and improving mitochondrial homeostasis, proposing this vitamin as an excellent candidate for delaying aging. However, the mechanisms around these processes are not yet fully explored. Therefore, in this review, the effects of vitamin D on redox regulation and cellular senescence are discussed to propose new lines of research and clinical applications of vitamin D in the context of age-related diseases.


Assuntos
Senescência Celular , Vitamina D , Humanos , Vitamina D/metabolismo , Oxirredução , Estresse Oxidativo , Vitaminas/farmacologia , Raios Ultravioleta
17.
Bratisl Lek Listy ; 123(11): 828-832, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36254641

RESUMO

BACKGROUND: Sepsis is one of the leading causes of death in intensive care units worldwide. Vitamins C and E are natural antioxidants and anti-inflammatory agents. Suppressing the inflammation is an important treatment target because it plays a role in the pathophysiology of sepsis. The purpose of this study was to investigate the effect of vitamins C and E treatment in rats with sepsis-induced lung damage. METHODS: In this animal study, fecal intraperitoneal injection procedure (FIP) was performed on 30 of 40 rats included for creating a sepsis model. Rats were randomly assigned into four groups: Group 1, control group (no procedure was applied, n = 10), Group 2, FIP (untreated septic group n = 10), Group 3, FIP+vitC (treated with 500 mg/kg/day ascorbic acid, n = 10), and Group 4, FIP+vitE (treated with 300 mg/kg/day alpha-tocopherol, n = 10). Chest CT was performed in all rats and density of the lungs was measured by using Hounsfield unit (HU). Histopathological examination of lung damage was performed, and blood samples were collected for biochemical analysis. RESULTS: TNF-α, CRP, IL 1-ß, IL-6, and MDA plasma levels in groups treated with vitamin C or vitamin E were lower than in the FIP group. Histological scores in groups treated either with vitamin C or vitamin E were significantly lower as compared to those in the FIP group. The HU value of lung in groups treated wither with vitamin C or vitamin E were lower than that in the FIP group (p < 0.05). CONCLUSION: The rats treated either with vitamin C or E showed improved results for sepsis. We think that they can be used as adjuvant therapy for septic patients because of their effectivity and low costs (Tab. 3, Fig. 2, Ref. 27).


Assuntos
Ácido Ascórbico , Sepse , Animais , Anti-Inflamatórios , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Interleucina-1 , Interleucina-6 , Pulmão , Ratos , Sepse/tratamento farmacológico , Tomografia Computadorizada por Raios X , Fator de Necrose Tumoral alfa , Vitamina E/farmacologia , Vitamina E/uso terapêutico , Vitaminas/farmacologia , Vitaminas/uso terapêutico , alfa-Tocoferol
18.
Pharmacol Res ; 186: 106484, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36206958

RESUMO

BACKGROUND: Vitamin D supplementation has attracted a lot of attention as a potential modulator of inflammation and oxidative stress, while some studies have reported controversial findings. In this regard, the purpose of this study was to summarize existing systematic reviews and meta-analyses of clinical trials that determined the effects of supplementation with vitamin D on inflammatory and oxidative biomarkers. METHODS: The following international databases were systematically searched till March 20th, 2022: PubMed, Scopus, Embase, Web of Science, and Google Scholar. A random-effects model was applied to evaluate the effects of vitamin D on inflammatory and oxidative stress biomarkers. RESULTS: Overall, 23 meta-analyses were qualified in this umbrella meta-analysis. Our findings revealed that the vitamin D supplementation significantly reduced serum C-reactive protein (CRP) (ES = -0.42; 95% CI: -0.55, -0.29, p < 0.001), tumor necrosis factor-α (TNF-α) (ES = -0.27; 95% CI: -0.42, -0.12; p < 0.001), and malondialdehyde (MDA) concentrations (ES = -0.37; 95% CI: -0.48, -0.25, p < 0.001). However, no significant changes were illustrated regarding interleukin-6 (IL-6) (ES = -0.35, 95% CI: -0.80, 0.10; p = 0.125), total antioxidant capacity (TAC) (ES = 0.68; 95% CI: -0.31, 1.66, p = 0.179), and glutathione (GSH) activity (ES = 0.08; 95% CI: -0.44, 0.60, p = 0.757). CONCLUSION: The present umbrella meta-analysis indicated that supplementation of vitamin D in adults can improve CRP, TNF-α, and MDA levels under various health conditions. Vitamin D could be considered an adjuvant therapy for relieving inflammation and oxidative stress.


Assuntos
Suplementos Nutricionais , Fator de Necrose Tumoral alfa , Adulto , Humanos , Fator de Necrose Tumoral alfa/metabolismo , Estresse Oxidativo , Biomarcadores , Vitamina D/uso terapêutico , Vitamina D/farmacologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Proteína C-Reativa/metabolismo , Vitaminas/uso terapêutico , Vitaminas/farmacologia , Glutationa/metabolismo
19.
Int J Mol Sci ; 23(20)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36293144

RESUMO

The highly transmittable and infectious COVID-19 remains a major threat worldwide, with the elderly and comorbid individuals being the most vulnerable. While vaccines are currently available, therapeutic drugs will help ease the viral outbreak and prevent serious health outcomes. Epigenetic modifications regulate gene expression through changes in chromatin structure and have been linked to viral pathophysiology. Since epigenetic modifications contribute to the life cycle of the virus and host immune responses to infection, epigenetic drugs are promising treatment targets to ameliorate COVID-19. Deficiency of the multifunctional secosteroid hormone vitamin D is a global health threat. Vitamin D and its receptor function to regulate genes involved in immunity, apoptosis, proliferation, differentiation, and inflammation. Amassed evidence also indicates the biological relations of vitamin D with reduced disease risk, while its receptor can be modulated by epigenetic mechanisms. The immunomodulatory effects of vitamin D suggest a role for vitamin D as a COVID-19 therapeutic agent. Therefore, this review highlights the epigenetic effects on COVID-19 and vitamin D while also proposing a role for vitamin D in COVID-19 infections.


Assuntos
COVID-19 , Deficiência de Vitamina D , Humanos , Idoso , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Vitamina D/metabolismo , SARS-CoV-2 , Vitaminas/farmacologia , Vitaminas/uso terapêutico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/genética , Deficiência de Vitamina D/tratamento farmacológico , Epigênese Genética , Hormônios , Cromatina
20.
Int J Mol Sci ; 23(20)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36293182

RESUMO

A balanced and varied diet provides diverse beneficial effects on health, such as adequate micronutrient availability and a gut microbiome in homeostasis. Besides their participation in biochemical processes as cofactors and coenzymes, vitamins and minerals have an immunoregulatory function; meanwhile, gut microbiota and its metabolites coordinate directly and indirectly the cell response through the interaction with the host receptors. Malnourishment is a crucial risk factor for several pathologies, and its involvement during the Coronavirus Disease 2019 pandemic has been reported. This pandemic has caused a significant decline in the worldwide population, especially those with chronic diseases, reduced physical activity, and elder age. Diet and gut microbiota composition are probable causes for this susceptibility, and its supplementation can play a role in reestablishing microbial homeostasis and improving immunity response against Coronavirus Disease 2019 infection and recovery. This study reviews the role of micronutrients and microbiomes in the risk of infection, the severity of disease, and the Coronavirus Disease 2019 sequelae.


Assuntos
COVID-19 , Microbioma Gastrointestinal , Humanos , Idoso , Micronutrientes/farmacologia , Vitaminas/farmacologia , Coenzimas
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