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1.
Aging Clin Exp Res ; 32(10): 2115-2131, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32865757

RESUMO

BACKGROUND: In December 2019, a novel human-infecting coronavirus, SARS-CoV-2, had emerged. The WHO has classified the epidemic as a "public health emergency of international concern". A dramatic situation has unfolded with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a deficiency in fat-soluble and hydrosoluble vitamins. METHODS: We searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We set them as a paradigm with the purpose to uncover common pathogenetic mechanisms between these pathological conditions and SARS-CoV-2 infection. Furthermore, we searched for studies describing the possible efficacy of vitamins A, D, E, and C in improving the immune system function. RESULTS: SARS-CoV-2 infection induces strong immune system dysfunction characterized by the development of an intense proinflammatory response in the host, and the development of a life-threatening condition defined as cytokine release syndrome (CRS). This leads to acute respiratory syndrome (ARDS), mainly in aged people. High mortality and lethality rates have been observed in elderly subjects with CoV-2-related infection. CONCLUSIONS: Vitamins may shift the proinflammatory Th17-mediated immune response arising in autoimmune diseases towards a T-cell regulatory phenotype. This review discusses the possible activity of vitamins A, D, E, and C in restoring normal antiviral immune system function and the potential therapeutic role of these micronutrients as part of a therapeutic strategy against SARS-CoV-2 infection.


Assuntos
Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/dietoterapia , Infecções por Coronavirus/prevenção & controle , Citocinas/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/dietoterapia , Pneumonia Viral/prevenção & controle , Vitaminas/imunologia , Vitaminas/uso terapêutico , Idoso , Ácido Ascórbico/imunologia , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Humanos , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Vitamina A/imunologia , Vitamina A/farmacologia , Vitamina A/uso terapêutico , Vitamina D/imunologia , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Vitamina E/imunologia , Vitamina E/farmacologia , Vitamina E/uso terapêutico , Vitaminas/farmacologia
2.
Aging Clin Exp Res ; 32(10): 2115-2131, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: covidwho-738008

RESUMO

BACKGROUND: In December 2019, a novel human-infecting coronavirus, SARS-CoV-2, had emerged. The WHO has classified the epidemic as a "public health emergency of international concern". A dramatic situation has unfolded with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a deficiency in fat-soluble and hydrosoluble vitamins. METHODS: We searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We set them as a paradigm with the purpose to uncover common pathogenetic mechanisms between these pathological conditions and SARS-CoV-2 infection. Furthermore, we searched for studies describing the possible efficacy of vitamins A, D, E, and C in improving the immune system function. RESULTS: SARS-CoV-2 infection induces strong immune system dysfunction characterized by the development of an intense proinflammatory response in the host, and the development of a life-threatening condition defined as cytokine release syndrome (CRS). This leads to acute respiratory syndrome (ARDS), mainly in aged people. High mortality and lethality rates have been observed in elderly subjects with CoV-2-related infection. CONCLUSIONS: Vitamins may shift the proinflammatory Th17-mediated immune response arising in autoimmune diseases towards a T-cell regulatory phenotype. This review discusses the possible activity of vitamins A, D, E, and C in restoring normal antiviral immune system function and the potential therapeutic role of these micronutrients as part of a therapeutic strategy against SARS-CoV-2 infection.


Assuntos
Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/dietoterapia , Infecções por Coronavirus/prevenção & controle , Citocinas/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/dietoterapia , Pneumonia Viral/prevenção & controle , Vitaminas/imunologia , Vitaminas/uso terapêutico , Idoso , Ácido Ascórbico/imunologia , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Humanos , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Vitamina A/imunologia , Vitamina A/farmacologia , Vitamina A/uso terapêutico , Vitamina D/imunologia , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Vitamina E/imunologia , Vitamina E/farmacologia , Vitamina E/uso terapêutico , Vitaminas/farmacologia
3.
Ecotoxicol Environ Saf ; 205: 111337, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979804

RESUMO

Iron overload in water is a problem in many areas of the world, which could exert toxic effects on fish. To achieve maximum growth and overall fitness, iron induced toxicity must be alleviated. Therefore, this research was undertaken to investigate the potential mitigation of iron toxicity by dietary vitamin C supplementation in channel catfish (Ictalurus punctatus). Two doses of vitamin C (143 and 573 mg/kg diet) were tested against high environmental iron (HEI, 9.5 mg/L representing 25% of 96 h LC50). Fish were randomly divided into six groups with four replicated tanks. The groups were Control (vitamin C deficient feed), LVc (143 mg vitamin C supplemented per kg diet), HVc (573 mg vitamin C supplemented per kg diet), Con + Fe (control exposed to HEI), LVc + Fe (LVc exposed to HEI) and HVc + Fe (HVc exposed to HEI). Following an 8 week trial, there was a significant reduction in weight gain (WG%) in Con + Fe compared to the control, indicating a toxic effect of HEI on fish growth performance. Interestingly, WG% in both LVc + Fe and HVc + Fe groups were significantly higher than Cont + Fe, signifying that HEI inhibited growth, but this was alleviated by vitamin C. Both hemoglobin content and hematocrit were higher in LVc + Fe compared to the control and Con + Fe. In addition, exposure to HEI (Con + Fe) incited hepatic oxidative stress based on an over-accumulation of malondialdehyde (MDA) along with a significant inhibition in superoxide dismutase (SOD) and catalase (CAT) activities; whereas in LVc + Fe and HVc + Fe, the MDA content restored to basal level. A series of histopathological alterations were observed in the liver and gills, with the most severe lesions in Con + Fe, which was also complemented with a remarkable increase in hepatic iron accumulation. Vitamin C supplementations reduced the augmented concentrations of iron accumulation to that of the control. No effect, regardless of the treatments, was noted for fatty acid composition of muscle. Overall, our findings suggest that the vitamin C supplementation can be an effective therapeutic approach for boosting growth as well as alleviating iron toxicity in catfish.


Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Ictaluridae/metabolismo , Ferro/toxicidade , Poluentes Químicos da Água/toxicidade , Ração Animal , Animais , Antioxidantes/metabolismo , Dieta , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Ferro/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Poluentes Químicos da Água/metabolismo
4.
J Med Life ; 13(2): 138-143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32742504

RESUMO

Treatment with anticancer drugs such as cyclophosphamide can harm the male reproductive system. Vitamin C and zinc are micronutrients with antioxidant activity and are the essential components of semen. Therefore, this study aimed to evaluate whether cyclophosphamide-exposed mice can recover from fertility with vitamin C and zinc therapy. In this experimental study, fifty male mice were divided into five groups. Groups 1-4 received cyclophosphamide (100 mg/kg, once a week for eight weeks). Also, group 2 received zinc (200 mg/kg), group 3 received vitamin C (300 mg/kg), group 4 received zinc and vitamin C (200 mg/kg and 300 mg/kg, respectively), five times per week for eight weeks, and group 5 received normal saline once a week and water five days a week for eight weeks. The data collected were statistically analyzed using SPSS 22. Results showed a significant increase in mount latency and a significant decrease in the number of sperms in the cyclophosphamide group compared to the control group. However, mount latency has been significantly decreased in mice treated with cyclophosphamide plus zinc compared to the cyclophosphamide group. The study also showed that the sperm count in the group that received cyclophosphamide and zinc had been increased compared to the cyclophosphamide group; the other treatments have decreased mount latency and increased the sperm count compared to the group treated with cyclophosphamide but not significantly. The Tubule Differentiation Index showed an increase in the cyclophosphamide-Zinc-Vitamin C group in comparison with the cyclophosphamide group. The current study showed that zinc could improve cyclophosphamide-induced toxicity of the reproductive system in male mice.


Assuntos
Antineoplásicos/efeitos adversos , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Substâncias Protetoras/farmacologia , Reprodução/efeitos dos fármacos , Zinco/farmacologia , Animais , Ácido Ascórbico/administração & dosagem , Ciclofosfamida/efeitos adversos , Hormônios/metabolismo , Humanos , Masculino , Camundongos , Comportamento Sexual Animal/efeitos dos fármacos , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos
5.
Nat Commun ; 11(1): 3637, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32686685

RESUMO

We report a strategy to boost Fenton reaction triggered by an exogenous circularly polarized magnetic field (MF) to enhance ferroptosis-like cell-death mediated immune response, as well as endow a responsive MRI capability by using a hybrid core-shell vesicles (HCSVs). HCSVs are prepared by loading ascorbic acid (AA) in the core and poly(lactic-co-glycolic acid) shell incorporating iron oxide nanocubes (IONCs). MF triggers the release of AA, resulting in the increase of ferrous ions through the redox reaction between AA and IONCs. A significant tumor suppression is achieved by Fenton reaction-mediated ferroptosis-like cell-death. The oxidative stress induced by the Fenton reaction leads to the exposure of calreticulin on tumor cells, which leads to dendritic cells maturation and the infiltration of cytotoxic T lymphocytes in tumor. Furthermore, the depletion of ferric ions during treatment enables monitoring of the Fe reaction in MRI-R2* signal change. This strategy provides a perspective on ferroptosis-based immunotherapy.


Assuntos
Ferroptose/efeitos dos fármacos , Campos Magnéticos , Nanopartículas de Magnetita , Neoplasias/terapia , Animais , Ácido Ascórbico/farmacologia , Calreticulina/metabolismo , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Compostos Férricos/química , Imunoterapia/métodos , Imagem por Ressonância Magnética , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Camundongos , Nanomedicina/métodos , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/imunologia , Estresse Oxidativo , Linfócitos T Citotóxicos/metabolismo
6.
Toxicol Lett ; 332: 118-129, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32659471

RESUMO

Silver-based antimicrobials are widely used topically to treat infections associated with multi-drug resistant (MDR) pathogens. Expanding this topical use to aerosols to treat lung infections requires understanding and preventing silver toxicity in the respiratory tract. A key mechanism resulting in silver-induced toxicity is the production of reactive oxygen species (ROS). In this study, we have verified ROS generation in silver-treated bronchial epithelial cells prompting evaluation of three antioxidants, N-acetyl cysteine (NAC), ascorbic acid, and melatonin, to identify potential prophylactic agents. Among them, NAC was the only candidate that abrogated the ROS generation in response to silver acetate exposure resulting in the rescue of these cells from silver-associated toxicity. Further, this protective effect directly translated to preservation of metabolic activity, as demonstrated by the normal levels of citric acid cycle metabolites in NAC-pretreated silver acetate-exposed cells. Because the citric acid cycle remained functional, silver-exposed cells pre-incubated with NAC demonstrated significantly higher levels of adenosine triphosphate levels compared with NAC-free controls. Moreover, we found that this prodigious capacity of NAC to rescue silver acetate-exposed cells was due not only to its antioxidant activity, but also to its ability to directly bind silver. Despite binding to silver, NAC did not alter the antimicrobial activity of silver acetate.


Assuntos
Acetilcisteína/farmacologia , Antibacterianos/farmacologia , Depuradores de Radicais Livres/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Prata/farmacologia , Prata/toxicidade , Acetatos/farmacologia , Trifosfato de Adenosina/metabolismo , Ácido Ascórbico/farmacologia , Linhagem Celular , Cromatografia Gasosa-Espectrometria de Massas , Glutationa/metabolismo , Humanos , Melatonina/farmacologia , Testes de Sensibilidade Microbiana , Compostos de Prata/farmacologia , Superóxidos/metabolismo
7.
Chemosphere ; 257: 127241, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32526468

RESUMO

The role of endogenous hydrogen sulphide (H2S) in silicon-induced improvement in boron toxicity (BT) tolerance in pepper plants was studied. Two-week old seedlings were subjected to control (0.05 mM B) or 2.0 mM BT in a nutrient solution. These two treatments were combined with 2.0 mM Si. BT caused considerable reduction in biomass, chlorophyll a &b, photosystem II maximum quantum efficiency (Fv/Fm), glutathione and ascorbate in the pepper seedlings. However, it enhanced malondialdehyde (MDA) and hydrogen peroxide, electrolyte leakage, proline, H2S, and activities of catalase, superoxide dismutase, peroxidase, and L-DES. Silicon stimulated growth, proline content and activities of various antioxidant biomolecules and enzymes, leaf Ca2+, K+ and N, endogenous H2S and L-DES activity, but reduced H2O2 and MDA contents, membrane leakage and leaf B. Silicon-induced B tolerance was further enhanced by 0.2 mM NaHS, a H2S donor. A scavenger of H2S, hypotaurine (0.1 mM HT), was supplied together with Si and Si + NaHS to assess the involvement of H2S in Si-induced BT tolerance of pepper plants. Hypotaurine inverted the positive role of Si on the antioxidant defence system by reducing endogenous H2S, but NaHS supply along with Si + HT reversed the negative effects of HT, showing that H2S participated in Si-induced BT tolerance of pepper plants.


Assuntos
Boro/toxicidade , Sulfeto de Hidrogênio/química , Poluentes do Solo/toxicidade , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Catalase/metabolismo , Clorofila A , Glutationa/metabolismo , Peróxido de Hidrogênio/farmacologia , Malondialdeído , Estresse Oxidativo/efeitos dos fármacos , Plântula/efeitos dos fármacos , Silício/química , Sulfetos , Superóxido Dismutase/metabolismo
8.
Chemosphere ; 251: 126424, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32443239

RESUMO

Phytoremediation via phyto-extraction is well recognized and sustainable principle for the economical removal of heavy metals from contaminated water and soil. The twofold objective of the present research work was to investigate the remediation potential of fenugreek for Cu under the influence of ascorbic acid (AA). The effect of copper-ascorbic acid chelation on the growth regulation of fenugreek (Trigonella foenum-graceum L.) and its potential to accumulate Cu was investigated in hydroponic medium to optimize concentration with complete randomized design (CRD). Juvenile fenugreek plants were treated with different treatments of AA (5 mM) and Cu (100, 250 and 500 µM). The different morpho-physiological parameters of fenugreek plant such as growth, biomass and chlorophylls were significantly reduced under Cu stress. However, the activities of antioxidant enzymes, electrolyte leakage and reactive oxygen species enhanced with increasing concentration of applied Cu. Results indicated significant increase in plant growth, biomass, physiology and antioxidant enzymes and decrease in reactive oxygen species and electrolyte production in AA mediated fenugreek plants compared to controls and Cu only treated plants. However, it was also found that AA enhanced Cu concentration maximum up to 42% in leaf, 18% in stem and 45% in roots as compared to Cu treated only plants. Moreover, application of AA signified the research results revealing to act as growth regulator and chelator under Cu stress.


Assuntos
Biodegradação Ambiental , Cobre/metabolismo , Poluentes do Solo/metabolismo , Trigonella/metabolismo , Antioxidantes/metabolismo , Ácido Ascórbico/farmacologia , Biomassa , Clorofila , Cobre/análise , Metais Pesados/metabolismo , Folhas de Planta/química , Raízes de Plantas/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Solo , Poluentes do Solo/análise
9.
Proc Natl Acad Sci U S A ; 117(23): 13033-13043, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32461362

RESUMO

Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogenital tract causing infections that range from asymptomatic to highly inflammatory. Recent works have highlighted the importance of histone modifications in the regulation of transcription and parasite pathogenesis. However, the nature of DNA methylation in the parasite remains unexplored. Using a combination of immunological techniques and ultrahigh-performance liquid chromatography (UHPLC), we analyzed the abundance of DNA methylation in strains with differential pathogenicity demonstrating that N6-methyladenine (6mA), and not 5-methylcytosine (5mC), is the main DNA methylation mark in T. vaginalis Genome-wide distribution of 6mA reveals that this mark is enriched at intergenic regions, with a preference for certain superfamilies of DNA transposable elements. We show that 6mA in T. vaginalis is associated with silencing when present on genes. Interestingly, bioinformatics analysis revealed the presence of transcriptionally active or repressive intervals flanked by 6mA-enriched regions, and results from chromatin conformation capture (3C) experiments suggest these 6mA flanked regions are in close spatial proximity. These associations were disrupted when parasites were treated with the demethylation activator ascorbic acid. This finding revealed a role for 6mA in modulating three-dimensional (3D) chromatin structure and gene expression in this divergent member of the Excavata.


Assuntos
Adenina/metabolismo , Cromatina/química , Metilação de DNA/genética , Trichomonas vaginalis/genética , Ácido Ascórbico/farmacologia , Técnicas de Cultura de Células , Cromatina/genética , Cromatina/metabolismo , Biologia Computacional , Metilação de DNA/efeitos dos fármacos , Elementos de DNA Transponíveis/genética , Regulação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Conformação Molecular , Análise de Sequência de DNA
10.
Toxicology ; 440: 152492, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32407874

RESUMO

Neurotoxicity induced by exposure to heavy metal lead (Pb) is a concern of utmost importance particularly for countries with industrial-based economies. The developing brain is especially sensitive to exposure to even minute quantities of Pb which can alter neurodevelopmental trajectory with irreversible effects on motor, emotive-social and cognitive attributes even into later adulthood. Chemical synapses form the major pathway of inter-neuronal communications and are prime candidates for higher order brain (motor, memory and behavior) functions and determine the resistance/susceptibility for neurological disorders, including neuropsychopathologies. The synaptic pathways and mechanisms underlying Pb-mediated alterations in neuronal signaling and plasticity are not completely understood. Employing a biochemically isolated synaptosomal fraction which is enriched in synaptic terminals and synaptic mitochondria, this study aimed to analyze the alterations in bioenergetic and redox/antioxidant status of cerebellar synapses induced by developmental exposure to Pb (0.2 %). Moreover, we test the efficacy of vitamin C (ascorbate; 500 mg/kg body weight), a neuroprotective and neuromodulatory antioxidant, in mitigation of Pb-induced neuronal deficits. Our results implicate redox and bioenergetic disruptions as an underlying feature of the synaptic dysfunction observed in developmental Pb neurotoxicity, potentially contributing to consequent deficits in motor, behavioral and psychological attributes of the organisms. In addition, we establish ascorbate as a key ingredient for therapeutic approach against Pb induced neurotoxicity, particularly for early-life exposures.


Assuntos
Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Cerebelo/metabolismo , Metabolismo Energético/efeitos dos fármacos , Intoxicação do Sistema Nervoso por Chumbo/patologia , Sinapses/metabolismo , Animais , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Cerebelo/efeitos dos fármacos , Feminino , Glutationa/metabolismo , Chumbo/sangue , Intoxicação do Sistema Nervoso por Chumbo/psicologia , Masculino , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Ratos , Ratos Wistar , Sinapses/efeitos dos fármacos , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo
11.
Nat Commun ; 11(1): 2332, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393788

RESUMO

Fasting-mimicking diets delay tumor progression and sensitize a wide range of tumors to chemotherapy, but their therapeutic potential in combination with non-cytotoxic compounds is poorly understood. Here we show that vitamin C anticancer activity is limited by the up-regulation of the stress-inducible protein heme-oxygenase-1. The fasting-mimicking diet selectivity reverses vitamin C-induced up-regulation of heme-oxygenase-1 and ferritin in KRAS-mutant cancer cells, consequently increasing reactive iron, oxygen species, and cell death; an effect further potentiated by chemotherapy. In support of a potential role of ferritin in colorectal cancer progression, an analysis of The Cancer Genome Atlas Database indicates that KRAS mutated colorectal cancer patients with low intratumor ferritin mRNA levels display longer 3- and 5-year overall survival. Collectively, our data indicate that the combination of a fasting-mimicking diet and vitamin C represents a promising low toxicity intervention to be tested in randomized clinical trials against colorectal cancer and possibly other KRAS mutated tumors.


Assuntos
Ácido Ascórbico/farmacologia , Dieta , Jejum/fisiologia , Mutação/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Progressão da Doença , Heme Oxigenase-1/metabolismo , Humanos , Ferro/metabolismo , Camundongos Endogâmicos BALB C , Oxaliplatina/farmacologia , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Análise de Sobrevida , Transferrina/metabolismo
12.
Am J Respir Cell Mol Biol ; 63(3): 362-373, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32374624

RESUMO

Defective airway mucus clearance is a defining characteristic of cystic fibrosis lung disease, and improvements to current mucolytic strategies are needed. Novel approaches targeting a range of contributing mechanisms are in various stages of preclinical and clinical development. ARINA-1 is a new nebulized product comprised of ascorbic acid, glutathione, and bicarbonate. Using microoptical coherence tomography, we tested the effect of ARINA-1 on central features of mucociliary clearance in F508del/F508del primary human bronchial epithelial cells to assess its potential as a mucoactive therapy in cystic fibrosis. We found that ARINA-1 significantly augmented mucociliary transport rates, both alone and with CFTR (cystic fibrosis transmembrane conductance regulator) modulator therapy, whereas airway hydration and ciliary beating were largely unchanged compared with PBS vehicle control. Analysis of mucus reflectivity and particle-tracking microrheology indicated that ARINA-1 restores mucus clearance by principally reducing mucus layer viscosity. The combination of bicarbonate and glutathione elicited increases in mucociliary transport rate comparable to those seen with ARINA-1, indicating the importance of this interaction to the impact of ARINA-1 on mucus transport; this effect was not recapitulated with bicarbonate alone or bicarbonate combined with ascorbic acid. Assessment of CFTR chloride transport revealed an increase in CFTR-mediated chloride secretion in response to ARINA-1 in CFBE41o- cells expressing wild-type CFTR, driven by CFTR activity stimulation by ascorbate. This response was absent in CFBE41o- F508del cells treated with VX-809 and primary human bronchial epithelial cells, implicating CFTR-independent mechanisms for the effect of ARINA-1 on cystic fibrosis mucus. Together, these studies indicate that ARINA-1 is a novel potential therapy for the treatment of impaired mucus clearance in cystic fibrosis.


Assuntos
Ácido Ascórbico/farmacologia , Bicarbonatos/farmacologia , Fibrose Cística/tratamento farmacológico , Glutationa/farmacologia , Transporte de Íons/efeitos dos fármacos , Depuração Mucociliar/efeitos dos fármacos , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Humanos
13.
Anticancer Res ; 40(4): 1963-1972, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234885

RESUMO

BACKGROUND/AIM: The menadione/ascorbate (M/A) combination has attracted attention due to the unusual ability of pro-vitamin/vitamin combination to kill cancer cells without affecting the viability of normal cells. The aim of this study was to elucidate the role of M/A in targeting cancerous mitochondria. MATERIALS AND METHODS: Several cancer and normal cell lines of the same origin were used. Cells were treated with different concentrations of M/A for 24 h. The cell viability, mitochondrial superoxide, mitochondrial membrane potential, and succinate were analyzed using conventional analytical tests. RESULTS: M/A exhibited a highly specific suppression on cancer cell growth and viability, without adversely affecting the viability of normal cells at concentrations attainable by oral or parenteral administration in vivo. This effect was accompanied by: (i) an extremely high production of mitochondrial superoxide in cancer cells, but not in normal cells; (ii) a significant dose-dependent depolarization of mitochondrial membrane and depletion of oncometabolite succinate in cancer cells. CONCLUSION: The anticancer effect of M/A is related to the induction of severe mitochondrial oxidative stress in cancer cells only. Thus, M/A has a potential to increase the sensitivity and vulnerability of cancer cells to conventional anticancer therapy and immune system.


Assuntos
Ácido Ascórbico/farmacologia , Mitocôndrias/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Vitamina K 3/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/patologia , Neoplasias/genética , Neoplasias/patologia , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/genética , Superóxidos/metabolismo
14.
Nutrients ; 12(4)2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32344708

RESUMO

Novel coronaviruses (CoV) have emerged periodically around the world in recent years. The recurrent spreading of CoVs imposes an ongoing threat to global health and the economy. Since no specific therapy for these CoVs is available, any beneficial approach (including nutritional and dietary approach) is worth investigation. Based on recent advances in nutrients and phytonutrients research, a novel combination of vitamin C, curcumin and glycyrrhizic acid (VCG Plus) was developed that has potential against CoV infection. System biology tools were applied to explore the potential of VCG Plus in modulating targets and pathways relevant to immune and inflammation responses. Gene target acquisition, gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment were conducted consecutively along with network analysis. The results show that VCG Plus can act on 88 hub targets which are closely connected and associated with immune and inflammatory responses. Specifically, VCG Plus has the potential to regulate innate immune response by acting on NOD-like and Toll-like signaling pathways to promote interferons production, activate and balance T-cells, and regulate the inflammatory response by inhibiting PI3K/AKT, NF-κB and MAPK signaling pathways. All these biological processes and pathways have been well documented in CoV infections studies. Therefore, our findings suggest that VCG Plus may be helpful in regulating immune response to combat CoV infections and inhibit excessive inflammatory responses to prevent the onset of cytokine storm. However, further in vitro and in vivo experiments are warranted to validate the current findings with system biology tools. Our current approach provides a new strategy in predicting formulation rationale when developing new dietary supplements.


Assuntos
Ácido Ascórbico/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Curcumina/uso terapêutico , Ácido Glicirrízico/uso terapêutico , Imunidade Inata/efeitos dos fármacos , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ácido Ascórbico/farmacologia , Coronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Curcuma/química , Curcumina/farmacologia , Citocinas/metabolismo , Combinação de Medicamentos , Sistemas de Liberação de Medicamentos , Ontologia Genética , Glycyrrhiza/química , Ácido Glicirrízico/farmacologia , Humanos , Interferons/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Transdução de Sinais , Biologia de Sistemas , Linfócitos T/metabolismo , Vitaminas/farmacologia , Vitaminas/uso terapêutico
15.
Nutrients ; 12(4)2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: covidwho-116799

RESUMO

Novel coronaviruses (CoV) have emerged periodically around the world in recent years. The recurrent spreading of CoVs imposes an ongoing threat to global health and the economy. Since no specific therapy for these CoVs is available, any beneficial approach (including nutritional and dietary approach) is worth investigation. Based on recent advances in nutrients and phytonutrients research, a novel combination of vitamin C, curcumin and glycyrrhizic acid (VCG Plus) was developed that has potential against CoV infection. System biology tools were applied to explore the potential of VCG Plus in modulating targets and pathways relevant to immune and inflammation responses. Gene target acquisition, gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment were conducted consecutively along with network analysis. The results show that VCG Plus can act on 88 hub targets which are closely connected and associated with immune and inflammatory responses. Specifically, VCG Plus has the potential to regulate innate immune response by acting on NOD-like and Toll-like signaling pathways to promote interferons production, activate and balance T-cells, and regulate the inflammatory response by inhibiting PI3K/AKT, NF-κB and MAPK signaling pathways. All these biological processes and pathways have been well documented in CoV infections studies. Therefore, our findings suggest that VCG Plus may be helpful in regulating immune response to combat CoV infections and inhibit excessive inflammatory responses to prevent the onset of cytokine storm. However, further in vitro and in vivo experiments are warranted to validate the current findings with system biology tools. Our current approach provides a new strategy in predicting formulation rationale when developing new dietary supplements.


Assuntos
Ácido Ascórbico/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Curcumina/uso terapêutico , Ácido Glicirrízico/uso terapêutico , Imunidade Inata/efeitos dos fármacos , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ácido Ascórbico/farmacologia , Coronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Curcuma/química , Curcumina/farmacologia , Citocinas/metabolismo , Combinação de Medicamentos , Sistemas de Liberação de Medicamentos , Ontologia Genética , Glycyrrhiza/química , Ácido Glicirrízico/farmacologia , Humanos , Interferons/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Transdução de Sinais , Biologia de Sistemas , Linfócitos T/metabolismo , Vitaminas/farmacologia , Vitaminas/uso terapêutico
16.
PLoS One ; 15(4): e0230774, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32240226

RESUMO

Oxidative stress is considered to be involved in the pathogenesis of primary blast-related traumatic brain injury (bTBI). We evaluated the effects of ascorbic acid 2-glucoside (AA2G), a well-known antioxidant, to control oxidative stress in rat brain exposed to laser-induced shock waves (LISWs). The design consisted of a controlled animal study using male 10-week-old Sprague-Dawley rats. The study was conducted at the University research laboratory. Low-impulse (54 Pa•s) LISWs were transcranially applied to rat brain. Rats were randomized to control group (anesthesia and head shaving, n = 10), LISW group (anesthesia, head shaving and LISW application, n = 10) or LISW + post AA2G group (AA2G administration after LISW application, n = 10) in the first study. In another study, rats were randomized to control group (n = 10), LISW group (n = 10) or LISW + pre and post AA2G group (AA2G administration before and after LISW application, n = 10). The measured outcomes were as follows: (i) motor function assessed by accelerating rotarod test; (ii) levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress marker; (iii) ascorbic acid in each group of rats. Ascorbic acid levels were significantly decreased and 8-OHdG levels were significantly increased in the cerebellum of the LISW group. Motor coordination disorder was also observed in the group. Prophylactic AA2G administration significantly increased the ascorbic acid levels, reduced oxidative stress and mitigated the motor dysfunction. In contrast, the effects of therapeutic AA2G administration alone were limited. The results suggest that the prophylactic administration of ascorbic acid can reduce shock wave-related oxidative stress and prevented motor dysfunction in rats.


Assuntos
Ácido Ascórbico/análogos & derivados , Ataxia/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Ácido Ascórbico/farmacologia , Encéfalo/efeitos dos fármacos , Lesões Encefálicas Traumáticas/tratamento farmacológico , Cerebelo/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley
17.
J Clin Pathol ; 73(5): 261-266, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32213553

RESUMO

AIMS: Staphylococcus aureus (S. aureus) is a life-threatening pathogen with high morbidity and mortality rates which causes nosocomial and community-acquired infections. Biofilm, considered to be a common virulence factor for pathogens, plays a significant role in recurrent and untreatable infections. Biofilm formation of S. aureus is mediated by synthesis of either poly-N-acetylglucosamine in an ica-dependent manner or surface proteins in an ica-independent manner. In some cases treatment is impossible and recurrent. In this study, ica-dependent biofilm-producing S. aureus isolates were detected and the anti-biofilm effect of ascorbic acid against biofilm formation of isolates was investigated. METHODS: A total of 21 methicillin-sensitive S. aureus (MSSA) clinical isolates stored in our bacterial stock were used to detect ica-dependent biofilm-producing MSSA isolates. The anti-biofilm study was undertaken with three ica-dependent biofilm-producing isolates (MSSA2-4) and ATCC 29213 (MSSA1). Biofilms and the anti-biofilm effect of ascorbic acid were detected using the microtitre plate (MtP) method. 16S-rRNA, nuc, icaA and icaD genes and expression levels of icaA and icaD of isolates were detected by RT-PCR. RESULTS: The minimum inhibitory concentrations (MICs) of ascorbic acid prevented biofilm formation of MSSA1 and MSSA3. Also, 1/2 MIC of ascorbic acid prevented biofilm formation of MSSA3. It was observed that biofilm formation decreased with increased concentration. There was no significant increase in ica gene expression of MSSA1 and MSSA2. Expression of icaA and icaD of MSSA3 decreased 13% and 38%, respectively. Expression of icaA in MSSA4 decreased 12%. CONCLUSION: The results of our study show that ascorbic acid can be used as an anti-biofilm agent to prevent biofilm formation of S. aureus and thus biofilm-related infections.


Assuntos
Antibacterianos/farmacologia , Ácido Ascórbico/farmacologia , Proteínas de Bactérias/metabolismo , Biofilmes/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Staphylococcus aureus/fisiologia
18.
Chemosphere ; 251: 126366, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32145575

RESUMO

In this study, the effects of excess nickel (Ni) (100 µM and 200 µM) on growth, antioxidant production, fatty acid, organic and amino acids profiles were examined in Lemna minor L. After 7 days of Ni treatment, chlorosis, growth inhibition and ROS overproduction were observed, accompanied by Ni accumulation. Interestingly, decreased malondialdehyde (MDA) levels were recorded in fronds upon Ni exposure. Fatty acid profiles in Ni-treated L. minor were characterized by increases in saturated- and decreases in unsaturated fatty acids. Ni excess increased the activities of antioxidant enzymes such as superoxide dismutase (SOD), guiacol peroxidase (GPX), and glutathione reductase (GR), and non-enzymatic antioxidants such as glutathione (GSH) and ascorbic acid (AsA); however, deactivation of ascorbate peroxidase (APX) and catalase (CAT) activities were also observed. Disruption of amino acid metabolism in Ni-exposed fronds was evidenced by the accumulation of cysteine, arginine, threonine, valine, isoleucine, leucine, lysine and phenylalanine, as well as reduced levels of tyrosine, alanine, aspartate and proline. Approximately 299%-396%, 139%-254% and 56%-97% concentration increments in citric, malic and oxalic acids, respectively, were concomitantly observed with significant decreases in tartaric, acetic, and fumaric acids in fronds subjected to Ni stress. Taken together, these results indicated that Ni stress induced negative effects on plant physiological, biochemical and morphological processes; however, it is likely that the coordination of metabolites and antioxidants may ameliorate the damaging effects of Ni accumulation.


Assuntos
Araceae/metabolismo , Níquel/metabolismo , Antioxidantes/metabolismo , Araceae/efeitos dos fármacos , Ascorbato Peroxidases/metabolismo , Ácido Ascórbico/farmacologia , Catalase/metabolismo , Ácidos Graxos/metabolismo , Glutationa/metabolismo , Glutationa Redutase/metabolismo , Malondialdeído/metabolismo , Oxirredução , Peroxidase/metabolismo , Peroxidases/metabolismo , Prolina/metabolismo , Superóxido Dismutase/metabolismo
19.
Life Sci ; 250: 117554, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32184123

RESUMO

BACKGROUND: Mental stress (MS) is related to endothelial dysfunction in overweight/obese men. It is believed that the pro-oxidant profile, associated with an imbalance in the vascular remodeling process, may contribute to deleterious effects of MS on endothelial function. However, it is unknown whether administration of ascorbic acid (AA), a potent antioxidant, can prevent oxidative and remodeling dysfunction during MS in these subjects. METHODS: Fourteen overweight/obese grade I men (27 ± 7 years; 29.7 ± 2.6 kg·m-2) underwent the Stroop Color Word Test for 5 min to induce MS after AA (3 g) or placebo (PL, 0.9% NaCl) intravenous infusions. Venous blood samples were collected at baseline and the last minute of MS to measure nitrite concentration (chemiluminescence), protein carbonylation, thiobarbituric acid reactive substances (TBARS) and catalase activity (colorimetric assays), superoxide dismutase (SOD; immunoenzymatic assay), activities of active/inactive (pro) forms of metalloproteinases-9 and -2 (MMP; zymography) and its respective tissue inhibitors concentration (TIMP-1 and TIMP-2; immunoenzymatic assays). RESULTS: At baseline, MMP-9 activity (p < 0.01), the MMP-9/proMMP-9 ratio (p = 0.02) and TIMP-1 concentration (p = 0.05) were reduced, whereas proMPP-9 activity was increased (p = 0.02) after AA compared to PL infusion. After PL infusion, MS increased protein carbonylation (p < 0.01), catalase (p < 0.01), and the MMP-9/proMMP-9 ratio (p = 0.04) when compared to baseline. AA infusion reduced protein carbonylation (p = 0.02), MMP-9 activity (p < 0.01), and MMP-9/pro-MMP-9 ratio (p < 0.01), while SOD (p = 0.04 vs baseline), proMPP-9 (p < 0.01 vs PL), MMP-2 (p < 0.01 vs PL) and TIMP-2 (p = 0.02 vs baseline) remained elevated during MS. CONCLUSIONS: AA appears to minimize the oxidative imbalance and vascular remodeling induced by MS.


Assuntos
Ácido Ascórbico/farmacologia , Obesidade/psicologia , Sobrepeso/psicologia , Estresse Psicológico , Remodelação Vascular/efeitos dos fármacos , Adulto , Antioxidantes/metabolismo , Catalase/metabolismo , Estudos Cross-Over , Endotélio Vascular/patologia , Humanos , Luminescência , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Oxidantes/metabolismo , Carbonilação Proteica , Fatores de Risco , Teste de Stroop , Superóxido Dismutase/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Adulto Jovem
20.
Chemosphere ; 244: 125579, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32050351

RESUMO

Although Solanum nigrum L. is a phytoremediator for different metals, its growth and physiology are still compromised by toxic levels of zinc (Zn). Thus, the development of eco-friendly strategies to enhance its tolerance, maintaining remediation potential is of special interest. This study evaluated the potential of 24-epibrassinolide (24-EBL) to boost S. nigrum defence against Zn towards a better growth rate and remediation potential. After 24 days of exposure, the results revealed that Zn-mediated inhibitory effects on biomass and biometry were efficiently mitigated upon application of 24-EBL, without affecting Zn accumulation. The evaluation of oxidative stress markers reported that Zn excess stimulated the accumulation of superoxide anion (O2.-), but reduced hydrogen peroxide (H2O2) levels, while not altering lipid peroxidation (LP). This was accompanied by an up-regulation of the antioxidant system, especially proline, superoxide dismutase (SOD) and ascorbate peroxidase (APX) in both organs, and ascorbate in roots of Zn-exposed plants. Foliar application of 24-EBL, however, induced distinctive effects, lowering proline levels in both organs, as well as APX activity in shoots and SOD in roots, whilst stimulating GSH and total thiols in both organs, as well as SOD and APX activity, in shoots and in roots, respectively. Probably due to a better antioxidant efficiency, levels of O2.- and H2O2 in pre-treated plants remained identical to the control, while LP further decreased in shoots. Overall, our results indicate a protective effect of 24-EBL on S. nigrum response to excess Zn, contributing for a better tolerance and growth rate, without disturbing its phytoremediation potential.


Assuntos
Brassinosteroides/metabolismo , Poluentes do Solo/toxicidade , Solanum nigrum/fisiologia , Esteroides Heterocíclicos/metabolismo , Zinco/toxicidade , Antioxidantes/farmacologia , Ascorbato Peroxidases/metabolismo , Ácido Ascórbico/farmacologia , Biodegradação Ambiental , Catalase/metabolismo , Peróxido de Hidrogênio/farmacologia , Peroxidação de Lipídeos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas/metabolismo , Superóxido Dismutase/metabolismo , Zinco/análise
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