RESUMO
Aim: To evaluate the behavior of oral keratinocytes in the presence of Vitamin C (Vit C) and its anti-inflammatory potential. Materials & methods: Oral keratinocytes were initially exposed to 0.1-2.5 mM of Vit C and the metabolic activity and cell migration were evaluated using MTS assay and Ibidi culture inserts, respectively. After, the cells were challenged with Candida albicans and inflammatory markers were analyzed by qPCR. Results: The treatment was not cytotoxic, and the highest concentrations increased the metabolic activity at 24 h. Vit C delayed the cell migration at 48 and 72 h. Interestingly, it downregulated the genes IL-8 and IL-1ß. Conclusion: Vit C could be an interesting adjuvant to anti-fungal treatment due to its anti-inflammatory potential.
Vitamin C, also known as ascorbic acid, is a vitamin commonly found in fruits and vegetables. It is popular for supporting our immune system, so is commonly taken as a supplement. We looked at the action of vitamin C on cells from the mouth and its potential to reduce inflammation in a fungal disease of the mouth oral candidiasis. We showed that vitamin C is not toxic to cells of the mouth and may reduce inflammation in cells infected by the fungus. This suggests that vitamin C could be used as a complementary therapy for oral candidiasis.
Assuntos
Anti-Inflamatórios , Ácido Ascórbico , Candida albicans , Movimento Celular , Queratinócitos , Candida albicans/efeitos dos fármacos , Candida albicans/imunologia , Ácido Ascórbico/farmacologia , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Queratinócitos/microbiologia , Queratinócitos/metabolismo , Anti-Inflamatórios/farmacologia , Movimento Celular/efeitos dos fármacos , Interleucina-8/metabolismo , Interleucina-8/genética , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Inflamação , Antifúngicos/farmacologiaRESUMO
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic and symmetric in-flammation. Our previous research revealed an imbalance in the gut flora of RA patients and showed that certain gut microbiota can accelerate RA progression by enhancing vitamin C degradation. However, it is unclear whether vitamin C supplementation could improve the gut microbiota to prevent the development of arthritis by interfering with the gut-joint axis. In this work, we aimed to evaluate the effects of vitamin C in regulating the gut microbiota and to elucidate its potential role in the onset and progression of RA in a mouse model, thus providing a basis for the development of new intervention strategies and treatments for RA. In this study, collagen-induced arthritis (CIA) mouse models, biochemical, histological and 16S rRNA microbiological methods were used to investigate the role and possible mechanism of vitamin C in rheumatoid arthritis. The results showed that treatment of CIA mice with vitamin C effectively rescued the gut mi-crobiota imbalance and suppressed the inflammatory response associated with RA, and effectively alleviated arthritis symptoms in mice in which levels of the pro-inflammatory cytokines IL-6 and TNF-α were specifi-cally reduced. In conclusion, our results demonstrate the potential of vitamin C as a potential therapeutic choice for RA.
Assuntos
Artrite Experimental , Artrite Reumatoide , Ácido Ascórbico , Microbioma Gastrointestinal , Animais , Ácido Ascórbico/uso terapêutico , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/microbiologia , Camundongos , Artrite Experimental/tratamento farmacológico , Artrite Experimental/microbiologia , Artrite Experimental/imunologia , Masculino , Camundongos Endogâmicos DBA , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Modelos Animais de Doenças , RNA Ribossômico 16S/genéticaRESUMO
Previous studies have shown that vitamin C (VC), an essential vitamin for the human body, can promote the differentiation of muscle satellite cells (MuSCs) in vitro and play an important role in skeletal muscle post-injury regeneration. However, the molecular mechanism of VC regulating MuSC proliferation has not been elucidated. In this study, the role of VC in promoting MuSC proliferation and its molecular mechanism were explored using cell molecular biology and animal experiments. The results showed that VC accelerates the progress of skeletal muscle post-injury regeneration by promoting MuSC proliferation in vivo. VC can also promote skeletal muscle regeneration in the case of atrophy. Using the C2C12 myoblast murine cell line, we observed that VC also stimulated cell proliferation. In addition, after an in vitro study establishing the occurrence of a physical interaction between VC and Pax7, we observed that VC also upregulated the total and nuclear Pax7 protein levels. This mechanism increased the expression of Myf5 (Myogenic Factor 5), a Pax7 target gene. This study establishes a theoretical foundation for understanding the regulatory mechanisms underlying VC-mediated MuSC proliferation and skeletal muscle regeneration. Moreover, it develops the application of VC in animal muscle nutritional supplements and treatment of skeletal muscle-related diseases.
Assuntos
Ácido Ascórbico , Proliferação de Células , Músculo Esquelético , Mioblastos , Fator de Transcrição PAX7 , Regeneração , Animais , Masculino , Camundongos , Ácido Ascórbico/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Fator Regulador Miogênico 5/metabolismo , Fator Regulador Miogênico 5/genética , Fator de Transcrição PAX7/metabolismo , Fator de Transcrição PAX7/genética , Regeneração/efeitos dos fármacos , Células Satélites de Músculo Esquelético/metabolismo , Células Satélites de Músculo Esquelético/efeitos dos fármacosRESUMO
AIMS: This study aimed to evaluate the effects of VC on SIMI in rats. METHODS: In this study, the survival rate of high dose VC for SIMI was evaluated within 7 days. Rats were randomly assigned to three groups: Sham group, CLP group, and high dose VC (500 mg/kg i.v.) group. The animals in each group were treated with drugs for 1 day, 3 days or 5 days, respectively. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1ß, IL-6, IL-10 and TNF-α) in serum were measured using ELISA kits. Western blot was used to detect proteins related to apoptosis, inflammation, autophagy, MAPK, NF-κB and PI3K/Akt/mTOR signaling pathways. RESULTS: High dose VC improved the survival rate of SIMI within 7 days. Echocardiography, HE staining and myocardial enzymes showed that high-dose VC relieved SIMI in rats in a time-dependent manner. And compared with CLP group, high-dose VC decreased the expressions of pro-apoptotic proteins, while increased the expression of anti-apoptotic protein. And compared with CLP group, high dose VC decreased phosphorylation levels of Erk1/2, P38, JNK, NF-κB and IKK α/ß in SIMI rats. High dose VC increased the expression of the protein Beclin-1 and LC3-II/LC3-I ratio, whereas decreased the expression of P62 in SIMI rats. Finally, high dose VC attenuated phosphorylation of PI3K, AKT and mTOR compared with the CLP group. SIGNIFICANCE: Our results showed that high dose VC has a good protective effect on SIMI after continuous treatment, which may be mediated by inhibiting apoptosis and inflammatory, and promoting autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR pathway.
Assuntos
Ácido Ascórbico , Autofagia , Traumatismos Cardíacos , Miocárdio , Sepse , Animais , Ratos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/administração & dosagem , Apoptose/efeitos dos fármacos , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Autofagia/efeitos dos fármacos , Traumatismos Cardíacos/tratamento farmacológico , Traumatismos Cardíacos/etiologia , Traumatismos Cardíacos/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Sepse/tratamento farmacológico , Sepse/complicações , Sepse/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
OBJECTIVE: Uterine serous carcinoma is a highly aggressive non-endometrioid subtype of endometrial cancer with poor survival rates overall, creating a strong need for new therapeutic strategies to improve outcomes. High-dose ascorbate (vitamin C) has been shown to inhibit cell proliferation and tumor growth in multiple preclinical models and has shown promising anti-tumor activity in combination with chemotherapy, with a favorable safety profile. We aimed to study the anti-tumor effects of ascorbate and its synergistic effect with carboplatin on uterine serous carcinoma cells. METHODS: Cell proliferation was evaluated by MTT and colony formation assays in ARK1, ARK2 and SPEC2 cells. Cellular stress, antioxidant ability, cleaved caspase 3 activity and adhesion were measured by ELISA assays. Cell cycle was detected by Cellometer. Invasion was measured using a wound healing assay. Changes in protein expression were determined by Western immunoblotting. RESULTS: High-dose ascorbate significantly inhibited cell proliferation, caused cell cycle arrest, induced cellular stress, and apoptosis, increased DNA damage, and suppressed cell invasion in ARK1 and SPEC2 cells. Treatment of both cells with 1 mM N-acetylcysteine reversed ascorbate-induced apoptosis and inhibition of cell proliferation. The combination of ascorbate and carboplatin produced significant synergistic effects in inhibiting cell proliferation and invasion, inducing cellular stress, causing DNA damage, and enhancing cleaved caspase 3 levels compared to each compound alone in both cells. CONCLUSIONS: Ascorbate has potent antitumor activity and acts synergistically with carboplatin through its pro-oxidant effects. Clinical trials of ascorbate combined with carboplatin as adjuvant treatment of uterine serous carcinoma are worth exploring.
Assuntos
Apoptose , Ácido Ascórbico , Carboplatina , Cistadenocarcinoma Seroso , Sinergismo Farmacológico , Neoplasias Uterinas , Ácido Ascórbico/farmacologia , Ácido Ascórbico/administração & dosagem , Humanos , Carboplatina/farmacologia , Carboplatina/administração & dosagem , Feminino , Linhagem Celular Tumoral , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/patologia , Neoplasias Uterinas/metabolismo , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/metabolismo , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Dano ao DNA/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/administração & dosagemRESUMO
Transcription initiates the formation of single-stranded DNA (ssDNA) regions within the genome, delineating transcription bubbles, a highly dynamic genomic process. Kethoxal-assisted single-stranded DNA sequencing (KAS-seq) utilizing N3-kethoxal has emerged as a potent tool for mapping specific guanine positions in ssDNA on a genome-wide scale. However, the original KAS-seq method required the costly Accel-NGS Methyl-seq DNA library kit. This study introduces an optimized iteration of the KAS-seq technique, referred to as adapter-tagged KAS-seq (atKAS-seq), incorporating an adapter tagging strategy. This modification involves integrating sequencing adapters via complementary strand synthesis using random N9 tagging. Additionally, by harnessing the potential of ascorbic acid (ASC), recognized for inducing global epigenetic changes, we employed the atKAS-seq methodology to elucidate critical pathways influenced by short-term, high-dose ASC treatment. Our findings underscore that atKAS-seq enables rapid and precise analyses of transcription dynamics and enhancer activities concurrently. This method offers a streamlined, cost-efficient, and low-input approach, affirming its utility in probing intricate genomic regulatory mechanisms.
Assuntos
Ácido Ascórbico , DNA de Cadeia Simples , Ácido Ascórbico/farmacologia , Butanonas , Sequências Reguladoras de Ácido Nucleico , Sequenciamento de Nucleotídeos em Larga Escala/métodosRESUMO
It is known that reactive oxygen species cause abnormal immune responses in the gut during inflammatory bowel diseases (IBD). Therefore, oxidative stress has been theorized as an agent of IBD development and antioxidant compounds such as vitamin C (L-ascorbic acid) have been studied as a new tool to treat IBD. Therefore, the potential of vitamin C to treat IBD was reviewed here as a critical discussion about this field and guide future research. Indeed, some preclinical studies have shown the beneficial effects of vitamin C in models of ulcerative colitis in mice and clinical and experimental findings have shown that deficiency in this vitamin is associated with the development of IBD and its worsening. The main mechanisms that may be involved in the activity of ascorbic acid in IBD include its well-established role as an antioxidant, but also others diversified actions. However, some experimental studies employed high doses of vitamin C and most of them did not perform dose-response curves and neither determined the minimum effective dose nor the ED50. Allometric extrapolations were also not made. Also, clinical studies on the subject are still in their infancy. Therefore, it is suggested that the research agenda in this matter covers experimental studies that assess the effective, safe, and translational doses, as well as the appropriate administration route and its action mechanism. After that, robust clinical trials to increase knowledge about the role of ascorbic acid deficiency in IBD patients and the effects of their supplementation in these patients can be encouraged.
Assuntos
Ácido Ascórbico , Doenças Inflamatórias Intestinais , Humanos , Animais , Camundongos , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Vitamina D/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológicoRESUMO
A systematic review and meta-analysis was conducted to assess the relationship between the common dietary antioxidants vitamin C, vitamin E, and ß-carotene and type 2 diabetes (T2D) and related traits. MEDLINE, Embase, and the Cochrane Library were searched for relevant publications up until May 2023. Studies were eligible if they had a cohort, case-control, or randomized controlled trial (RCT) design and examined dietary intake, supplementation, or circulating levels of these antioxidants as exposure, and insulin resistance, ß-cell function, or T2D incidence as outcomes. Summary relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI) were estimated using random-effects models. The certainty of the evidence was assessed with the Grading of Recommendations, Assessment, Development and Evaluations framework. Among 6190 screened records, 25 prospective observational studies and 15 RCTs were eligible. Inverse associations were found between dietary and circulating antioxidants and T2D (observational studies). The lowest risk was seen at intakes of 70 mg/d of vitamin C (RR: 0.76; CI: 0.61, 0.95), 12 mg/d of vitamin E (RR: 0.72; CI: 0.61, 0.86), and 4 mg/d of ß-carotene (RR: 0.78; CI: 0.65, 0.94). Supplementation with vitamin E (RR: 1.01; CI: 0.93, 1.10) or ß-carotene (RR: 0.98; CI: 0.90, 1.07) did not have a protective effect on T2D (RCTs), and data on vitamin C supplementation was limited. Regarding insulin resistance, higher dietary vitamin C (RR: 0.85; CI: 0.74, 0.98) and vitamin E supplementation (MD: -0.35; CI: -0.65, -0.06) were associated with a reduced risk. The certainty of evidence was high for the associations between T2D and dietary vitamin E and ß-carotene, and low to moderate for other associations. In conclusion, moderate intakes of vitamins C, E, and ß-carotene may lower risk of T2D by reducing insulin resistance. Lack of protection with supplementation in RCTs suggests that adequate rather than high intakes may play a role in T2D prevention. This systematic review and meta-analysis was registered in PROSPERO with registration number CRD42022343482.
Assuntos
Antioxidantes , Ácido Ascórbico , Diabetes Mellitus Tipo 2 , Suplementos Nutricionais , Vitamina E , beta Caroteno , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Mellitus Tipo 2/sangue , Humanos , beta Caroteno/administração & dosagem , beta Caroteno/farmacologia , beta Caroteno/sangue , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/farmacologia , Vitamina E/administração & dosagem , Vitamina E/farmacologia , Antioxidantes/administração & dosagem , Resistência à Insulina , Dieta , Fatores de Risco , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , IdosoRESUMO
The use of vitamin C (VC) in high doses demonstrates a potent tumor suppressive effect by mediating a glucose-dependent oxidative stress in Kirsten rat sarcoma (KRAS) mutant cancer cells. VC with arsenic trioxide (ATO) is a promising drug combination that might lead to the development of effective cancer therapeutics. Considering that a tumor suppressive effect of VC requires its high-dose administration, it is of interest to examine the toxicity of two enantiomers of VC (enantiomer d-optical isomer D-VC and natural l-optical isomer L-VC) in vitro and in vivo. We show that the combinations of L-VC with ATO and D-VC with ATO induced a similar cytotoxic oxidative stress in KrasG12D-expressing mutant cancer cells as indicated by a substantial increase in reactive oxidative species (ROS) production and depolarization of mitochondria. To examine the L-VC and D-VC toxicity effects, we administered high doses of D-VC and L-VC to CD1 mice and carried out an evaluation of their toxic effects. The daily injections of L-VC at a dose of 9.2 g/kg for 18 days were lethal to mice, while 80% of mice remained alive following the similar high-dose administration of D-VC. Following the drug injection courses and histopathological studies, we determined that a natural form of VC (L-VC) is more harmful and toxic to mice when compared to the effects caused by the similar doses of D-VC. Thus, our study indicates that the two enantiomers of VC have a similar potency in the induction of oxidative stress in cancer cells, but D-VC has a distinctive lower toxicity in mice compared to L-VC. While the mechanism of a distinctive toxicity between D-VC and L-VC is yet to be defined, our finding marks D-VC as a more preferable option compared to its natural enantiomer L-VC in clinical settings.
Assuntos
Ácido Ascórbico , Neoplasias , Animais , Camundongos , Ácido Ascórbico/farmacologia , Proteínas Proto-Oncogênicas p21(ras) , Estresse Oxidativo , Vitaminas/farmacologia , Trióxido de Arsênio/farmacologiaRESUMO
Currently, coronary artery bypass and reperfusion therapies are considered the gold standard in long-term treatments to restore heart function after acute myocardial infarction. As a drawback of these restoring strategies, reperfusion after an ischemic insult and sudden oxygen exposure lead to the exacerbated synthesis of additional reactive oxidative species and the persistence of increased oxidation levels. Attempts based on antioxidant treatment have failed to achieve an effective therapy for cardiovascular disease patients. The controversial use of vitamin C as an antioxidant in clinical practice is comprehensively systematized and discussed in this review. The dose-dependent adsorption and release kinetics mechanism of vitamin C is complex; however, this review may provide a holistic perspective on its potential as a preventive supplement and/or for combined precise and targeted therapeutics in cardiovascular management therapy.
Assuntos
Ácido Ascórbico , Infarto do Miocárdio , Humanos , Espécies Reativas de Oxigênio , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Vitamina E/uso terapêutico , Estresse Oxidativo , Vitaminas , Infarto do Miocárdio/tratamento farmacológicoRESUMO
Acute kidney injury frequently occurs after cardiac surgery, and is primarily attributed to renal ischemia-reperfusion (I/R) injury and inflammation from surgery and cardiopulmonary bypass. Vitamin C, an antioxidant that is often depleted in critically ill patients, could potentially mitigate I/R-induced oxidative stress at high doses. We investigated the effectiveness of high-dose vitamin C in preventing I/R-induced renal injury. The ideal time and optimal dosage for administration were determined in a two-phase experiment on Sprague-Dawley rats. The rats were assigned to four groups: sham, IRC (I/R + saline), and pre- and post-vitC (vitamin C before and after I/R, respectively), with vitamin C administered at 200â¯mg/kg. Additional groups were examined for dose modification based on the optimal timing determined: V100, V200, and V300 (100, 200, and 300â¯mg/kg, respectively). Renal I/R was achieved through 45â¯min of ischemia followed by 24â¯h of reperfusion. Vitamin C administration during reperfusion significantly reduced renal dysfunction and tubular damage, more than pre-ischemic administration. Doses of 100 and 200â¯mg/kg during reperfusion reduced oxidative stress markers, including myeloperoxidase and inflammatory responses by decreasing high mobility group box 1 release and nucleotide-binding and oligomerization domain-like receptor 3 inflammasome. Overall beneficial effect was most prominent with 200â¯mg/kg. The 300â¯mg/kg dose, however, showed no additional benefits over the IRC group regarding serum blood urea nitrogen and creatinine levels and histological evaluation. During reperfusion, high-dose vitamin C administration (200â¯mg/kg) significantly decreased renal I/R injury by effectively attenuating the major triggers of oxidative stress and inflammation.
Assuntos
Injúria Renal Aguda , Antineoplásicos , Traumatismo por Reperfusão , Humanos , Ratos , Animais , Ratos Sprague-Dawley , Rim , Estresse Oxidativo , Injúria Renal Aguda/metabolismo , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Ácido Ascórbico/metabolismo , Traumatismo por Reperfusão/patologia , Antineoplásicos/farmacologia , Inflamação/metabolismo , Isquemia/metabolismo , CreatininaRESUMO
OBJECTIVE: This study aimed to evaluate the effects of three antioxidants, selenium yeast capsule, vitamin E and vitamin C, alone or in combination, on the salivary glands of patients with differentiated thyroid cancer (DTC) treated with iodine-131 ( 131 I). METHODS: A total of 69 postoperative DTC patients were randomly divided into three groups: vitamin E combined with vitamin C group (21 cases); selenium yeast group (23 cases); and selenium yeast combined with vitamin C group (25 cases). Salivary gland functional changes were assessed by salivary gland dynamic imaging functional parameters in the enrolled patients before and 1 month after 131 I treatment. RESULTS: Comparison of salivary gland function parameters before and after 131 I treatment in the three groups were evaluated. In the vitamin E combined with the vitamin C group, the left parotid gland excretion fraction (EF) value was significantly higher than that before treatment. In the selenium yeast group, the left parotid gland excretion part, bilateral parotid gland excretion ratio (ER), left submandibular gland maximum uptake ratio within 20 min (UR20), and the right submandibular gland ER values were significantly higher than that before treatment, while in the selenium yeast combined with vitamin C group, the bilateral parotid gland EF, bilateral submandibular gland UR20, EF, and left submandibular gland ER values were significantly higher than that before treatment (all P < 0.05). CONCLUSION: During high-dose 131 I treatment, vitamin E combined with vitamin C improved the excretory function of parotid glands in DTC patients; selenium supplementation had a protective effect on salivary glands; and the combination of selenium and vitamin C had a better effect.
Assuntos
Selênio , Neoplasias da Glândula Tireoide , Humanos , Radioisótopos do Iodo/uso terapêutico , Antioxidantes/uso terapêutico , Antioxidantes/farmacologia , Selênio/farmacologia , Selênio/uso terapêutico , Saccharomyces cerevisiae , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Glândulas Salivares , Glândula Parótida , Vitamina E/farmacologia , Vitamina E/uso terapêutico , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêuticoRESUMO
BACKGROUND: Food allergy has become a global public health problem. This study aimed to explore the possible anti-allergic effect of vitamin C (VC). A rat basophilic leukemia (RBL)-2H3 cell degranulation model was used to assess the effect of VC on degranulation in vitro, and an ovalbumin (OVA)-induced BALB/c mouse allergy model was used to assess the anti-allergy effect of VC in vivo. RESULTS: In vitro, VC significantly attenuated the release of ß-hexosaminidase, tryptase and histamine, and also reduced cytokine production (interleukins 4 and 6, tumor necrosis factor α) significantly (P < 0.05), with the inhibitory effect demonstrating a positive correlation with VC dose. In vivo, compared with the OVA group, the levels of serum immunoglobulins E and G1 of the VC low-dose (VCL) group (50 mg kg-1) and high-dose (VCH) group (200 mg·kg-1) were significantly reduced (P < 0.05). Furthermore, the plasma histamine level was also significantly decreased (P < 0.05). Moreover, TH2 cell polarization in mice of the VCL and VCH groups was significantly inhibited (P < 0.05), promoting the TH1/TH2 cell polarization balance. Additionally, VC treatment enhanced the expression of CD80 (P < 0.05) in spleen and small intestine tissues, while significantly inhibiting the expression of CD86 (P < 0.05); notably, high-dose VC treatment was more effective. CONCLUSION: VC exerted an anti-allergic effect through inhibiting degranulation and regulating TH1/TH2 cell polarization balance. © 2024 Society of Chemical Industry.
Assuntos
Antialérgicos , Ácido Ascórbico , Degranulação Celular , Hipersensibilidade Alimentar , Camundongos Endogâmicos BALB C , Células Th1 , Células Th2 , Animais , Células Th2/imunologia , Células Th2/efeitos dos fármacos , Antialérgicos/farmacologia , Camundongos , Ácido Ascórbico/farmacologia , Degranulação Celular/efeitos dos fármacos , Células Th1/imunologia , Células Th1/efeitos dos fármacos , Ratos , Hipersensibilidade Alimentar/tratamento farmacológico , Hipersensibilidade Alimentar/imunologia , Imunoglobulina E/imunologia , Humanos , Feminino , Masculino , Ovalbumina/imunologia , Ovalbumina/efeitos adversos , Citocinas/metabolismo , Citocinas/imunologia , beta-N-Acetil-Hexosaminidases/metabolismoRESUMO
Depression is linked with oxidative stress and inflammation, where key players include nitric oxide (NO), nuclear factor erythroid 2-related factor 2 (Nrf2), Brain-Derived Neurotrophic Factor (BDNF), and Heme Oxidase-1 (HO-1). Augmenting the efficacy of antidepressants represents a compelling avenue of exploration. We explored the potential of vitamins C and D as adjuncts to escitalopram (Esc) in a lipopolysaccharide (LPS)-induced depression model focusing on the aforementioned biomarkers. Male Swiss albino mice were stratified into distinct groups: control, LPS, LPS + Esc, LPS + Esc + Vit C, LPS + Esc + Vit D, and LPS + Esc + Vit C + Vit D. After a 7-day treatment period, a single LPS dose (2 mg/kg), was administered, followed by comprehensive assessments of behavior and biochemical parameters. Notably, a statistically significant (p < 0.05) alleviation of depressive symptoms was discerned in the Esc + Vit C + Vit D group versus the LPS group, albeit with concomitant pronounced sedation evident in all LPS-treated groups (p < 0.05). Within the cortex, LPS reduced (p < 0.05) the expression levels of NOx, Nrf2, BDNF, and HO-1, with only HO-1 being reinstated to baseline in the LPS + Esc + Vit D and the LPS + Esc + Vit C + Vit D groups. Conversely, the hippocampal NOx, Nrf2, and HO-1 levels remained unaltered following LPS administration. Notably, the combination of Esc, Vit C, and Vit D effectively restored hippocampal BDNF levels, which had been diminished by Esc alone. In conclusion, vitamins C and D enhance the therapeutic effects of escitalopram through a mechanism independent of Nrf2. These findings underscore the imperative need for in-depth investigations.
Assuntos
Escitalopram , Lipopolissacarídeos , Camundongos , Animais , Masculino , Lipopolissacarídeos/farmacologia , Depressão/tratamento farmacológico , Depressão/metabolismo , Ácido Ascórbico/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Vitaminas , Adjuvantes Imunológicos , Vitamina D , Modelos AnimaisRESUMO
This study used 300 1-day-old, sexless, developing chicks of Japanese quail to estimate the ability of vitamin C and/or garlic to antagonize the venomous influence of cadmium (Cd) on the hematological, immunological, and performance characteristics of developing Japanese quail. The quail was separated into 5 similar groups of 60 chicks apiece, and 6 duplicates (10 each) were given to each sub-group. The control group received a basal diet without any supplements. The Cd group was nourished with a basal diet of + 80 mg cadmium chloride (CdCl2)/kg diet. The 3rd group was fed a basal diet + 80 mg CdCl2/kg diet and complemented with a 200 mg Vitamin C (Cd + C)/kg diet. The 4th group was nourished with a basal diet + 80 mg CdCl2/kg diet and complemented by a 500 mg dried garlic powder (Cd + G)/kg diet. The 5th group was fed a basal diet + 80 mg CdCl2/kg diet, complemented by a 200 mg vitamin C/kg diet + 500 mg dried garlic powder (Cd + CG)/kg diet. Results showed that in the 5th group in which cadmium was added together with Vit C + garlic, there was an improvement in both live weight gain (1-42 d) and feed consumption (1-21 and 1-42 d ) compared to the group in which Cd was added alone. The addition of Vit C alone and together with garlic seems to completely improve the cadmium-related increase in alkaline phosphatase (ALP), and Aspartate aminotransferase (AST), and Malondialdehyde (MDA) levels when compared to the control. Compared to cadmium-polluted diets, quail that got cadmium and feed additives significantly reduced cadmium residue. In addition, the cadmium group's serum immunoglobulin M (IgM) level decreased significantly. These data imply that dietary supplementation with (C) or (G) may be beneficial in retrogressing the drop in immunoglobulin G (IgG) and IgM caused by Cd and minimizing Cd's deleterious influence on immunity.
Assuntos
Ácido Ascórbico , Alho , Animais , Ácido Ascórbico/farmacologia , Coturnix , Cádmio/toxicidade , Pós , Galinhas , Antioxidantes/farmacologia , Vitaminas , Suplementos Nutricionais , Dieta/veterinária , Codorniz , Imunoglobulina M , Ração Animal/análiseRESUMO
BACKGROUND: After myocardial infarction, the lost myocardium is replaced by fibrotic tissue, eventually progressively leading to myocardial dysfunction. Direct reprogramming of fibroblasts into cardiomyocytes via the forced overexpression of cardiac transcription factors Gata4, Mef2c, and Tbx5 (GMT) offers a promising strategy for cardiac repair. The limited reprogramming efficiency of this approach, however, remains a significant challenge. METHODS: We screened seven factors capable of improving direct cardiac reprogramming of both mice and human fibroblasts by evaluating small molecules known to be involved in cardiomyocyte differentiation or promoting human-induced pluripotent stem cell reprogramming. RESULTS: We found that vitamin C (VitC) significantly increased cardiac reprogramming efficiency when added to GMT-overexpressing fibroblasts from human and mice in 2D and 3D model. We observed a significant increase in reactive oxygen species (ROS) generation in human and mice fibroblasts upon Doxy induction, and ROS generation was subsequently reduced upon VitC treatment, associated with increased reprogramming efficiency. However, upon treatment with dehydroascorbic acid, a structural analog of VitC but lacking antioxidant properties, no difference in reprogramming efficiency was observed, suggesting that the effect of VitC in enhancing cardiac reprogramming is partly dependent of its antioxidant properties. CONCLUSIONS: Our findings demonstrate that VitC supplementation significantly enhances the efficiency of cardiac reprogramming, partially by suppressing ROS production in the presence of GMT.
Assuntos
Antioxidantes , Ácido Ascórbico , Humanos , Camundongos , Animais , Espécies Reativas de Oxigênio , Ácido Ascórbico/farmacologia , Antioxidantes/farmacologia , Reprogramação Celular , Proteínas com Domínio T/genética , Fatores de Transcrição MEF2/genética , Miócitos Cardíacos , Vitaminas , FibroblastosRESUMO
The objective of this study was to investigate how supplementing vitamin C (VC) in milk affects growth, starter intake, blood metabolites, and the health of young calves classified into healthy or diarrheic groups. Calves were classified as diarrheic if they experienced diarrhea for at least 3 days from birth to day 7, otherwise, they were classified as healthy (i.e., days with diarrhea < 3). From day 8 of age, a total of 48 Holstein calves were divided into four groups based on a 2 × 2 factorial arrangement, with calf health status (healthy or diarrheic) and VC supplementation (VC+ or VC-) to pasteurized milk (0 or 2 g/d; 50% purity) being the main experimental factors. Calves were fed equal amounts of milk until weaning (d 60). Calves continued to be monitored until they reached 74 days of age. Calves in the VC+ group were heavier at weaning (74.3 vs. 72.2 kg; P = 0.04) compared to those calves that did not receive VC. Blood total antioxidant capacity (d 53 and 67) and superoxide dismutase activity (d 53) were greater (P < 0.01) in VC+ vs. VC- calves. Calf health status and VC supplementation interacted (P = 0.03) for blood ß-hydroxybutyrate on d 53, with the lowest concentration observed in diarrheic/VC- calves. Calves in the diarrheic group had a lower total antioxidant capacity (P = 0.01) but a greater neutrophil-to-lymphocyte ratio on d 53 and 67 (P < 0.01) than calves in the healthy group. Before weaning (d 53), neutrophil-to-lymphocyte ratio was greater, but hemoglobin was lower (P = 0.02) in calves classified into the diarrheic group that did not receive supplemental VC. The number of days medicated for diarrhea treatment was lower in VC+ calves than those in VC- group (1.73 vs. 2.47 days; P = 0.05). Overall, VC supplementation in pasteurized milk improved calf growth and health. Calves that experienced elevated episodes of diarrhea within the first week of life benefited more from supplemental VC than those classified into the healthy group.
Assuntos
Dieta , Leite , Animais , Bovinos , Leite/metabolismo , Dieta/veterinária , Antioxidantes/metabolismo , Peso Corporal , Desmame , Diarreia/prevenção & controle , Diarreia/veterinária , Vitaminas/metabolismo , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Ácido Ascórbico/metabolismo , Ração Animal/análise , Suplementos NutricionaisRESUMO
An experiment was carried out to assess the efficacy of supplemental ascorbic acid (AA) on broiler chicken production performance, blood haematological profile, biochemical profile, and carcass traits under heat stress conditions. A total of 192-day-old broiler chicks were divided into four groups, each with six replicates of eight each (4 × 6 × 8). Four corn-based dietary treatments were formulated: T1 (control diet), T2 (T1 + AA at 200 mg/kg), T3 (T1 + AA at 400 mg/kg), and T4 (T1 + AA at 600 mg/kg) for a period of 42 days. Despite the high temperature and humidity, the 600 mg AA supplemental groups (T4) gained significantly (P ≤ 0.05) more body weight and had a higher feed intake and better feed conversion ratio (FCR) than the control group (T1). After 28 days of feeding the three AA-supplemented diets, antibody titres (humoral immune response) were significantly higher (P ≤ 0.05). The response to intradermally injected phyto-haemagglutinin (PHA-P), an index of the in vivo cell-mediated immune response, was found to be increased (P ≤ 0.05) in the 400 and 600 mg AA-supplemented groups after 35 days. Higher levels of AA (T4) supplementation significantly (P ≤ 0.05) improved haematological values such as haemoglobin (Hb), total erythrocyte count (TEC), total leukocyte count (TLC), and differential leukocyte count (DLC), heterophil:lymphocyte (H:L) in comparison to the control group (T1). The supplemented group improved the serum biochemical profile of the birds, with an increase (P ≤ 0.05) in total serum protein, albumin, and globulin and a decrease in serum cholesterol and corticosterone levels in the T4 group compared to the control group. Heat shock protein-70 (HSP-70) was gradually elevated after increasing the ascorbic acid concentration (P ≤ 0.05) at 14 and 21 days. As a result, it can be concluded that supplementing ascorbic acid at 600 mg/kg is beneficial for improving the performance, immunity, and blood haematological biochemical profile and upregulating the HSP-70 gene of broiler chickens under heat stress conditions.
Assuntos
Ácido Ascórbico , Galinhas , Animais , Ração Animal/análise , Ácido Ascórbico/farmacologia , Galinhas/metabolismo , Dieta/veterinária , Suplementos Nutricionais , Resposta ao Choque TérmicoRESUMO
Heat stress is a significant factor affecting the fertility of dairy cattle due to the generation of free radicals. In assisted reproductive techniques, the inclusion of protective antioxidants becomes crucial to mitigate potential cellular damage. This study aimed to explore the impact of supplementing vitamins E, C, and coenzyme Q10 into the oocyte culture medium, with the goal of ameliorating the adverse effects of heat stress on oocyte maturation and embryo development in dairy cattle. A group of fifty Holstein dairy cows were synchronized, and their oocytes were harvested using the ovum pick-up method. High-quality oocytes were subjected to in vitro maturation (IVM) and in vitro fertilization (IVF) procedures, utilizing a culture medium containing, no supplements (Group 1), 100 µM of vitamins E (Group 2) and C (Group 3), along with 50 µM of coenzyme Q10 (Group 4). The ensuing zygotes were cultured, and the ensuing embryos were evaluated for blastocyst formation by the seventh day. An analysis of the blastocysts' inner cell mass (ICM) and trophectoderm (TE) cells was also conducted. The findings revealed that the group receiving supplementation of vitamin E and coenzyme Q10 exhibited significantly higher maturation and cleavage rates in comparison to both the control and the vitamin C groups. Furthermore, the count of ICM, TE, and blastocyst cells was notably elevated in the vitamin E supplemented group when compared to the control group. In summary, the effectiveness of vitamin E in enhancing IVM, IVF, and embryo development under conditions of heat stress surpassed that of vitamin C and coenzyme Q10.
Assuntos
Técnicas de Maturação in Vitro de Oócitos , Ubiquinona/análogos & derivados , Vitamina E , Animais , Feminino , Bovinos , Técnicas de Maturação in Vitro de Oócitos/veterinária , Vitamina E/farmacologia , Oócitos , Desenvolvimento Embrionário , Suplementos Nutricionais , Vitaminas/farmacologia , Ácido Ascórbico/farmacologia , Resposta ao Choque TérmicoRESUMO
BACKGROUND: Ascorbic acid (AA) is an antioxidant that might be beneficial for adjunctive treatment of sepsis in horses. The optimal dose and effects on oxidative status are unknown. HYPOTHESIS: Ascorbic acid administration will increase plasma AA concentrations and decrease determinants of reactive oxygen metabolites (dROM), basal and stimulant-induced intraerythrocytic reactive oxygen species (ROS) concentrations, and stimulant-induced neutrophil ROS production, and increase plasma antioxidant capacity (PAC) in a dose-dependent manner. ANIMALS: Eight healthy horses. METHODS: Randomized placebo-controlled crossover study. Each horse received 4 single-dose IV treatments including AA at 25, 50, and 100 mg/kg and saline (placebo) with each treatment separated by ≥1 week. Blood was collected at baseline, 2 and 6 hours for assessment of plasma dROM and PAC via photometer, intraerythrocytic ROS by flow cytometry, and stimulant-induced neutrophil ROS by a fluorometric assay. Plasma AA concentrations were measured by high-performance liquid chromatography/electrochemical detection. RESULTS: Ascorbic acid at 100 mg/kg resulted in decreased dROM 2 hours after treatment (P = .03, 95% CI 5.51-121.2, point estimate 63.3). There was no effect of AA on basal or stimulant-induced intraerythrocytic ROS (P = .88, 95% CI -0.156 to 0.081, point estimate -0.037; P = .93, 95% CI -0.123 to 0.112, point estimate -0.006, respectively), basal or stimulant-induced neutrophil ROS (P ≥ .12, 95% CI -644.9 to 56.2, point estimate -294.4), or PAC (P ≥ .64, 95% CI -1567 to 463.4, point estimate -552.0) at any dose or timepoint. Plasma AA concentrations increased in a dose-dependent manner. CONCLUSIONS AND CLINICAL IMPORTANCE: High-dose administration of AA might provide antioxidant benefits in horses.