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1.
Nat Commun ; 11(1): 4938, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009401

RESUMO

Antiviral strategies to inhibit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here, we demonstrate that the NRF2 antioxidant gene expression pathway is suppressed in biopsies obtained from COVID-19 patients. Further, we uncover that NRF2 agonists 4-octyl-itaconate (4-OI) and the clinically approved dimethyl fumarate (DMF) induce a cellular antiviral program that potently inhibits replication of SARS-CoV2 across cell lines. The inhibitory effect of 4-OI and DMF extends to the replication of several other pathogenic viruses including Herpes Simplex Virus-1 and-2, Vaccinia virus, and Zika virus through a type I interferon (IFN)-independent mechanism. In addition, 4-OI and DMF limit host inflammatory responses to SARS-CoV2 infection associated with airway COVID-19 pathology. In conclusion, NRF2 agonists 4-OI and DMF induce a distinct IFN-independent antiviral program that is broadly effective in limiting virus replication and in suppressing the pro-inflammatory responses of human pathogenic viruses, including SARS-CoV2.


Assuntos
Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Fumarato de Dimetilo/agonistas , Fator 2 Relacionado a NF-E2/metabolismo , Pneumonia Viral/tratamento farmacológico , Succinatos/agonistas , Adulto , Antioxidantes/farmacologia , Betacoronavirus/metabolismo , Infecções por Coronavirus/virologia , Fumarato de Dimetilo/farmacologia , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Interferon Tipo I , Pulmão/patologia , Masculino , Fator 2 Relacionado a NF-E2/genética , Pandemias , Pneumonia Viral/virologia , Transdução de Sinais/efeitos dos fármacos , Succinatos/farmacologia , Replicação Viral/efeitos dos fármacos
2.
Biochemistry (Mosc) ; 85(7): 833-837, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33040727

RESUMO

Nrf2 is a key transcription factor responsible for antioxidant defense in many tissues and cells, including alveolar epithelium, endothelium, and macrophages. Furthermore, Nrf2 functions as a transcriptional repressor that inhibits expression of the inflammatory cytokines in macrophages. Critically ill patients with COVID-19 infection often present signs of high oxidative stress and systemic inflammation - the leading causes of mortality. This article suggests rationale for the use of Nrf2 inducers to prevent development of an excessive inflammatory response in COVID-19 patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/metabolismo , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Terapia de Alvo Molecular/métodos , Fator 2 Relacionado a NF-E2/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/metabolismo , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Catequina/análogos & derivados , Catequina/farmacologia , Catequina/uso terapêutico , Infecções por Coronavirus/virologia , Fumarato de Dimetilo/farmacologia , Fumarato de Dimetilo/uso terapêutico , Feminino , Humanos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Inflamação/metabolismo , Isotiocianatos/farmacologia , Isotiocianatos/uso terapêutico , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Pandemias , Pneumonia Viral/virologia , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/metabolismo , Síndrome do Desconforto Respiratório do Adulto/virologia , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Tiossulfatos/farmacologia , Tiossulfatos/uso terapêutico
4.
Oxid Med Cell Longev ; 2020: 8384742, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32963703

RESUMO

H2 has shown anti-inflammatory and antioxidant ability in many clinical trials, and its application is recommended in the latest Chinese novel coronavirus pneumonia (NCP) treatment guidelines. Clinical experiments have revealed the surprising finding that H2 gas may protect the lungs and extrapulmonary organs from pathological stimuli in NCP patients. The potential mechanisms underlying the action of H2 gas are not clear. H2 gas may regulate the anti-inflammatory and antioxidant activity, mitochondrial energy metabolism, endoplasmic reticulum stress, the immune system, and cell death (apoptosis, autophagy, pyroptosis, ferroptosis, and circadian clock, among others) and has therapeutic potential for many systemic diseases. This paper reviews the basic research and the latest clinical applications of H2 gas in multiorgan system diseases to establish strategies for the clinical treatment for various diseases.


Assuntos
Hidrogênio/administração & dosagem , Hidrogênio/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Betacoronavirus , Infecções por Coronavirus/terapia , Metabolismo Energético/efeitos dos fármacos , Humanos , Estresse Oxidativo/efeitos dos fármacos , Pandemias , Pneumonia Viral/terapia , Substâncias Protetoras/farmacologia
5.
Int J Med Sci ; 17(14): 2133-2146, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922174

RESUMO

The SARS-CoV-2 spread quickly across the globe. The World Health Organization (WHO) on March 11 declared COVID-19 a pandemic. The mortality rate, hospital disorders and incalculable economic and social damages, besides the unproven efficacy of the treatments evaluated against COVID-19, raised the need for immediate control of this disease. Therefore, the current study employed in silico tools to rationally identify new possible SARS-CoV-2 main protease (Mpro) inhibitors. That is an enzyme conserved among the coronavirus species; hence, the identification of an Mpro inhibitor is to make it a broad-spectrum drug. Molecular docking studies described the binding sites and the interaction energies of 74 Mpro-ligand complexes deposited in the Protein Data Bank (PDB). A structural similarity screening was carried out in order to identify possible Mpro ligands that show additional pharmacological properties against COVID-19. We identified 59 hit compounds and among them, melatonin stood out due to its prominent immunomodulatory and anti-inflammatory activities; it can reduce oxidative stress, defence cell mobility and efficiently combat the cytokine storm and sepsis. In addition, melatonin is an inhibitor of calmodulin, an essential intracellular component to maintain angiotensin-converting enzyme 2 (ACE-2) on the cell surface. Interestingly, one of the most promising hits in our docking study was melatonin. It revealed better interaction energy with Mpro compared to ligands in complexes from PDB. Consequently, melatonin can have response potential in early stages for its possible effects on ACE-2 and Mpro, although it is also promising in more severe stages of the disease for its action against hyper-inflammation. These results definitely do not confirm antiviral activity, but can rather be used as a basis for further preclinical and clinical trials.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Descoberta de Drogas , Melatonina/farmacologia , Pneumonia Viral/tratamento farmacológico , Proteínas não Estruturais Virais/antagonistas & inibidores , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Cisteína Endopeptidases , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Melatonina/uso terapêutico , Simulação de Acoplamento Molecular , Pandemias , Pneumonia Viral/virologia , Inibidores de Proteases/farmacologia , Inibidores de Proteases/uso terapêutico
6.
Biomed Environ Sci ; 33(8): 593-602, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32933611

RESUMO

Objective: This study aimed to investigate the effect of exposure to a 900 MHz electromagnetic field (EMF) on the cervical spinal cord (CSC) of rats and the possible protective effect of luteolin (LUT) against CSC tissue damage. Methods: Quantitative data were obtained via stereological, biochemical, immunohistochemical, and histopathological techniques. We investigated morphometric value, superoxide dismutase (SOD) level, and the expression of high-mobility group box 1 protein molecules, as well as histological changes. Results: The total number of motor neurons in the EMF group significantly decreased in comparison with that in the control group ( P < 0.05). In the EMF + LUT group, we found a significant increase in the total number of motor neurons compared with that in the EMF group ( P < 0.05). SOD enzyme activity in the EMF group significantly increased in comparison with that in the control group ( P < 0.05). By contrast, the EMF+LUT group exhibited a decrease in SOD level compared with the EMF group ( P < 0.05). Conclusion: Our results suggested that exposure to EMF could be deleterious to CSC tissues. Furthermore, the protective efficacy of LUT against SC damage might have resulted from the alleviation of oxidative stress caused by EMF.


Assuntos
Antioxidantes/farmacologia , Campos Eletromagnéticos/efeitos adversos , Luteolina/farmacologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/efeitos da radiação , Animais , Masculino , Ratos , Ratos Wistar
7.
Anticancer Res ; 40(9): 5201-5210, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878808

RESUMO

BACKGROUND/AIM: Persimmon (Diospyros kaki L.) leaves are popular as a tea infusion in Asia and their main active ingredients are flavonoids. The present study aimed to explore the anticancer properties of flavonoids isolated from persimmon leaves (PLF). MATERIALS AND METHODS: We investigated the in vitro anti-proliferative activity of PLF against several human cancer cell lines. Apoptosis and intracellular reactive oxygen species (ROS) induced by PLF were accessed using high-content analysis with florescent staining. The ability of PLF to scavenge free radicals was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. RESULTS: PLF demonstrated significant inhibition of proliferation of liver, breast, and colorectal cancer cells in vitro. PLF induced apoptosis and increased intracellular ROS levels in HCT116 (colorectal cancer) and HepG2 (liver cancer) cells. In addition, PLF showed strong free radical scavenging ability. CONCLUSION: The anti-proliferation activity of PLF against cancer cells was related to the induction of apoptosis and oxidative stress.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Diospyros/química , Flavonoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Flavonoides/química , Flavonoides/isolamento & purificação , Humanos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo
8.
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
9.
PLoS One ; 15(8): e0237536, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790719

RESUMO

Melatonin is effective in enhancing various abiotic stress resistances of plants. However, its underlying mechanisms in drought-resistance in winter wheat (Triticum aestivum L.) is not clear. The goal of this work was to investigate the effect of melatonin on seed germination and to evaluate leaf antioxidant physiology for two wheat varieties. Experiments included 20% PEG, melatonin plus 20% PEG and a control using two contrasting wheat varieties (JM22- drought sensitive and HG35- drought resistant). Melatonin levels were 0, 1, 10, 100 and 300 µmol L-1. Results revealed that 300 µmol L-1 of melatonin alleviated the negative effect of water stress on germination and increased radicle length, radicle number, and plumule length of the germinated seeds. Principal component analysis showed a significant change in amino acid content during germination and this change was dependent on melatonin concentration and the variety. Lysine (Lys) content in wheat seeds under the PEG plus 300 µmol L-1 melatonin treatment increased compared with that of the seeds under PEG alone. There was a significant and positive correlation between Lys content and morphological index of germination. During seedling growth, soluble protein was involved in osmotic adjustment and superoxide dismutase (SOD) activity was increased to mitigate the damage in the cytomembrane of JM 22 leaf under 300 µmol L-1 melatonin plus PEG treatment. The effect of melatonin was dependent on SOD activity increasing significantly for HG35-a drought resistant variety. The results of this work lays a foundation for further studies to determine if melatonin can be economically used to mitigate the impact of dry planting conditions on wheat productivity in North China Plain.


Assuntos
Antioxidantes/farmacologia , Germinação/efeitos dos fármacos , Melatonina/farmacologia , Polietilenoglicóis/toxicidade , Sementes/efeitos dos fármacos , Estresse Fisiológico , Triticum/efeitos dos fármacos , Secas , Osmose , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Triticum/crescimento & desenvolvimento , Triticum/metabolismo
10.
PLoS One ; 15(8): e0237613, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790786

RESUMO

BACKGROUND: Nordihydroguaiaretic acid (NDGA) is a plant extract that has been shown to act as a free radical scavenger and pluripotent inhibitor of pro-inflammatory cytokines, two major cellular processes involved in the pathophysiology of sepsis. We investigated whether NDGA would improve markers of organ injury as well as survival in a rodent model of sepsis. METHODS: Abdominal sepsis was induced by cecal ligation and double puncture (CLP) in male Sprague-Dawley rats. NDGA was administered either at the time of injury (pre-) or 6 hours later (post-treatment). A sham surgery group and a vehicle only group were also followed as controls. Blood and lung tissue were collected 24 h after CLP. Lung tissue was used for histopathologic analysis and to measure pulmonary edema. Arterial oxygenation was measured directly to generate PaO2/FiO2, and markers of renal injury (blood urea nitrogen), liver injury (alanine aminotransferase), and tissue hypoxia (lactate) were measured. In a separate set of animals consisting of the same treatment groups, animals were followed for up to 36 hours for survival. RESULTS: NDGA pre-treatment resulted in improved oxygenation, less lung edema, lower lactate, lower BUN, and reduced histologic lung injury. NDGA post-treatment resulted in less lung edema, lower lactate, lower BUN, and less histologic lung injury, but did not significantly change oxygenation. None of the NDGA treatment groups statistically affected ALT or creatinine. NDGA pre-treatment showed improved survival compared with control CLP animals at 36 hours, while post-treatment did not. CONCLUSIONS: NDGA represents a novel pleiotropic anti-inflammatory agent with potential clinical utility for modulation of organ injury secondary to sepsis.


Assuntos
Antioxidantes/farmacologia , Ceco/cirurgia , Ligadura/efeitos adversos , Pneumopatias/tratamento farmacológico , Masoprocol/farmacologia , Punções/efeitos adversos , Sepse/cirurgia , Animais , Pneumopatias/etiologia , Pneumopatias/patologia , Masculino , Ratos , Ratos Sprague-Dawley
11.
Nat Commun ; 11(1): 4028, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32788591

RESUMO

Changes in atmospheric CO2 concentration have played a central role in algal and plant adaptation and evolution. The commercially important red algal genus, Pyropia (Bangiales) appears to have responded to inorganic carbon (Ci) availability by evolving alternating heteromorphic generations that occupy distinct habitats. The leafy gametophyte inhabits the intertidal zone that undergoes frequent emersion, whereas the sporophyte conchocelis bores into mollusk shells. Here, we analyze a high-quality genome assembly of Pyropia yezoensis to elucidate the interplay between Ci availability and life cycle evolution. We find horizontal gene transfers from bacteria and expansion of gene families (e.g. carbonic anhydrase, anti-oxidative related genes), many of which show gametophyte-specific expression or significant up-regulation in gametophyte in response to dehydration. In conchocelis, the release of HCO3- from shell promoted by carbonic anhydrase provides a source of Ci. This hypothesis is supported by the incorporation of 13C isotope by conchocelis when co-cultured with 13C-labeled CaCO3.


Assuntos
Carbono/metabolismo , Genoma , Rodófitas/genética , Rodófitas/metabolismo , Movimentos da Água , Exoesqueleto/química , Animais , Antioxidantes/farmacologia , Composição de Bases/genética , Evolução Biológica , Carbonato de Cálcio/metabolismo , Anidrases Carbônicas/genética , Anidrases Carbônicas/metabolismo , Núcleo Celular/genética , Dosagem de Genes , Perfilação da Expressão Gênica , Transferência Genética Horizontal/genética , Moluscos , Fotossíntese/efeitos dos fármacos , Ploidias , Rodófitas/efeitos dos fármacos , Superóxido Dismutase/genética , Transcrição Genética/efeitos dos fármacos
12.
Aquat Toxicol ; 227: 105596, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32827874

RESUMO

In aquatic animals, hypoxia is associated with growth retardation, impaired immunity, susceptibility to pathogens, oxidative stress, and mortality. However, the relative long-term effects of hypoxia on bivalves, including abalone, are not well understood. In this study, we examined the effects of exposure to hypoxic (2.5 and 4 mg O2 L-1) and normoxic (8 mg O2 L-1) conditions on the growth, survival, and immune and antioxidant responses of the economically important Pacific abalone Haliotis discus hannai over a 4 month period. We observed that exposure to 2.5 mg O2 L-1 resulted in marked reductions in assessed shell parameters, average meat weight, and survival compared with exposure to 4 and 8 mg O2 L-1. There were also significant reductions in oxygen consumption and ammonia-N excretion in abalone exposed to 2.5 mg O2 L-1. We also detected initial immunosuppression in the 2.5 mg O2 L-1-treated abalone, as evidenced by a significant reduction in total hemocytes and inhibition of antibacterial and lysozyme activities. Furthermore, intracellular malondialdehyde concentrations were significantly elevated at 1 month in the 2.5 mg O2 L-1 treatment group, whereas there were reductions in the levels of glutathione and enzymatic activities of catalase and superoxide dismutase, thereby indicating potential hypoxia-induced oxidative stress and a depression of antioxidant capacity. After 4 months of treatment, severe hypoxia (2.5 mg O2 L-1) had significantly modulated all measured parameters, whereas exposure to 4 and 8 mg O2 L-1 had induced no significant effects. Collectively, our observations indicate that under long-term exposure to hypoxia, Pacific abalone failed to maintain an effective antioxidant defense system and adequate immunity, with the observed biochemical disruptions leading to a reduction in growth and survival.


Assuntos
Eutrofização , Gastrópodes/imunologia , Imunidade Inata/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Catalase/farmacologia , Gastrópodes/efeitos dos fármacos , Hipóxia , Estresse Oxidativo , Estresse Fisiológico , Superóxido Dismutase , Poluentes Químicos da Água/toxicidade
13.
PLoS One ; 15(8): e0237986, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841282

RESUMO

Insects experience a diversity of subtoxic and/or toxic xenobiotics through exposure to pesticides and, in the case of herbivorous insects, through plant defensive compounds in their diets. Many insects are also concurrently exposed to antioxidants in their diets. The impact of dietary antioxidants on the toxicity of xenobiotics in insects is not well understood, in part due to the challenge of developing appropriate systems in which doses and exposure times (of both the antioxidants and the xenobiotics) can be controlled and outcomes can be easily measured. However, in Drosophila melanogaster, a well-established insect model system, both dietary factors and pesticide exposure can be easily controlled. Additionally, the mode of action and xenobiotic metabolism of dichlorodiphenyltrichloroethane (DDT), a highly persistent neurotoxic organochlorine insecticide that is detected widely in the environment, have been well studied in DDT-susceptible and -resistant strains. Using a glass-vial bioassay system with blue diet as the food source, seven compounds with known antioxidant effects (ascorbic acid, ß-carotene, glutathione, α-lipoic acid, melatonin, minocycline, and serotonin) were orally tested for their impact on DDT toxicity across three strains of D. melanogaster: one highly susceptible to DDT (Canton-S), one mildly susceptible (91-C), and one highly resistant (91-R). Three of the antioxidants (serotonin, ascorbic acid, and ß-carotene) significantly impacted the toxicity of DDT in one or more strains. Fly strain and gender, antioxidant type, and antioxidant dose all affected the relative toxicity of DDT. Our work demonstrates that dietary antioxidants can potentially alter the toxicity of a xenobiotic in an insect population.


Assuntos
Antioxidantes/farmacologia , DDT/toxicidade , Dieta , Drosophila melanogaster/efeitos dos fármacos , Resistência a Inseticidas/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Drosophila melanogaster/genética , Drosophila melanogaster/fisiologia , Feminino , Genótipo , Masculino , Serotonina/farmacologia , Caracteres Sexuais
14.
Life Sci ; 259: 118341, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32853653

RESUMO

Aging is a form of a gradual loss of physiological integrity that results in impaired cellular function and ultimately increased vulnerability to disease and death. This process is a significant risk factor for critical age-related disorders such as cancer, diabetes, cardiovascular disease, and neurological conditions. Several mechanisms contribute to aging, most notably progressive telomeres shortening, which can be counteracted by telomerase enzyme activity and increasing in this enzyme activity associated with partly delaying the onset of aging. Individual behaviors and environmental factors such as nutrition affect the life-span by impact the telomerase activity rate. Healthy eating habits, including antioxidant intakes, such as polyphenols, can have a positive effect on telomere length by this mechanism. In this review, after studying the underlying mechanisms of aging and understanding the relationships between telomeres, telomerase, and aging, it has been attempted to explain the effect of polyphenols on reversing the oxidative stress and aging process.


Assuntos
Antioxidantes/farmacologia , Plantago/efeitos dos fármacos , Polifenóis/farmacologia , Telômero/efeitos dos fármacos , Animais , Combinação de Medicamentos , Humanos , Extrato de Senna , Encurtamento do Telômero/efeitos dos fármacos
15.
Oxid Med Cell Longev ; 2020: 3173281, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32855764

RESUMO

The outbreaks of viruses with wide spread and mortality in the world population have motivated the research for new therapeutic approaches. There are several viruses that cause a biochemical imbalance in the infected cell resulting in oxidative stress. These effects may be associated with the development of pathologies and worsening of symptoms. Therefore, this review is aimed at discussing natural compounds with both antioxidant and antiviral activities, specifically against coronavirus infection, in an attempt to contribute to global researches for discovering effective therapeutic agents in the treatment of coronavirus infection and its severe clinical complications. The contribution of the possible action of these compounds on metabolic modulation associated with antiviral properties, in addition to other mechanisms of action, is presented.


Assuntos
Antioxidantes/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Coronavirus/efeitos dos fármacos , Animais , Antioxidantes/uso terapêutico , Coronavirus/patogenicidade , Infecções por Coronavirus/virologia , Humanos
16.
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
17.
Medicina (Kaunas) ; 56(8)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32752010

RESUMO

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes the corona virus disease-19 which is accompanied by severe pneumonia, pulmonary alveolar collapses and which stops oxygen exchange. Viral transmissibility and pathogenesis depend on recognition by a receptor in the host, protease cleavage of the host membrane and fusion. SARS-CoV-2 binds to the angiotensin converting enzyme 2 receptor. Here, we discuss the general characteristics of the virus, its mechanism of action and the way in which the mechanism correlates with the comorbidities that increase the death rate. We also discuss the currently proposed therapeutic measures and propose the use of antioxidant drugs to help patients infected with the SARS-CoV-2. Oxidizing agents come from phagocytic leukocytes such as neutrophils, monocytes, macrophages and eosinophils that invade tissue. Free radicals promote cytotoxicity thus injuring cells. They also trigger the mechanism of inflammation by mediating the activation of NFkB and inducing the transcription of cytokine production genes. Release of cytokines enhances the inflammatory response. Oxidative stress is elevated during critical illnesses and contributes to organ failure. In corona virus disease-19 there is an intense inflammatory response known as a cytokine storm that could be mediated by oxidative stress. Although antioxidant therapy has not been tested in corona virus disease-19, the consequences of antioxidant therapy in sepsis, acute respiratory distress syndrome and acute lung injury are known. It improves oxygenation rates, glutathione levels and strengthens the immune response. It reduces mechanical ventilation time, the length of stay in the intensive care unit, multiple organ dysfunctions and the length of stay in the hospital and mortality rates in acute lung injury/acute respiratory distress syndrome and could thus help patients with corona virus disease-19.


Assuntos
Antioxidantes/farmacologia , Betacoronavirus/fisiologia , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Humanos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia
18.
Nat Commun ; 11(1): 4178, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32826895

RESUMO

Friedreich's ataxia (FRDA) is an autosomal-recessive neurodegenerative and cardiac disorder which occurs when transcription of the FXN gene is silenced due to an excessive expansion of GAA repeats into its first intron. Herein, we generate dorsal root ganglia organoids (DRG organoids) by in vitro differentiation of human iPSCs. Bulk and single-cell RNA sequencing show that DRG organoids present a transcriptional signature similar to native DRGs and display the main peripheral sensory neuronal and glial cell subtypes. Furthermore, when co-cultured with human intrafusal muscle fibers, DRG organoid sensory neurons contact their peripheral targets and reconstitute the muscle spindle proprioceptive receptors. FRDA DRG organoids model some molecular and cellular deficits of the disease that are rescued when the entire FXN intron 1 is removed, and not with the excision of the expanded GAA tract. These results strongly suggest that removal of the repressed chromatin flanking the GAA tract might contribute to rescue FXN total expression and fully revert the pathological hallmarks of FRDA DRG neurons.


Assuntos
Ataxia de Friedreich/genética , Ataxia de Friedreich/patologia , Gânglios Espinais/metabolismo , Edição de Genes/métodos , Proteínas de Ligação ao Ferro/genética , Organoides/metabolismo , Células Receptoras Sensoriais/metabolismo , Antioxidantes/farmacologia , Sistemas CRISPR-Cas , Diferenciação Celular , Cromatina/metabolismo , Ataxia de Friedreich/tratamento farmacológico , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/patologia , Predisposição Genética para Doença/genética , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Íntrons , Mitocôndrias/metabolismo , Organoides/efeitos dos fármacos , Organoides/patologia , Células Receptoras Sensoriais/patologia , Análise de Sequência de RNA , Transcriptoma
19.
PLoS One ; 15(8): e0237076, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32750082

RESUMO

Drug resistant Salmonella species and shortcomings related to current drugs stress the urgent need to search for new antimicrobial agents to control salmonellosis. This study investigated the antisalmonellal and antioxidant potentials of methanolic and hydro-ethanolic extracts of Garcinia kola and Alchornea cordifolia as potential sources of drugs to control Salmonella species and to reduce related oxidative stress. The antisalmonellal activity was assessed using the broth microdilution, membrane destabilization and time-kill kinetic assays. While, the DPPH, ABTS and FRAP assays were used for the determination of the antioxidant activities. The minimum inhibitory concentrations ranged from 125 to 1000 µg/mL, with the methanolic root extract of G. kola being the most active. The time kill kinetic assay revealed a concentration-dependent bacteriostatic activity for promising extracts. Potent extracts from G. kola showed the ability to destabilize S. typhi outer membrane, with the methanolic root extract presenting the highest activity; two-fold higher than those of polymyxin B tested as reference. In addition, this methanolic root extract of G. kola also provoked nucleotide leakage in a concentration-dependent manner. From the antioxidant assays, the hydro-ethanolic extract from the stem bark of A. cordifolia presented significant activities comparable to that of Vitamin C. The methanolic root extract of G. kola also presented appreciable antioxidant activities, though less than that of A. cordifolia. Overall, the phytochemical screening of active extracts revealed the presence of anthocyanins, flavonoids, glycosides, phenols, tannins, triterpenoids and steroids. These results provide evidence of the antibacterial potential of G. kola and offer great perspectives in a possible standardisation of an antisalmonellal phytomedicine.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Euphorbiaceae/química , Garcinia kola/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Antocianinas/farmacologia , Camarões , Flavonoides/farmacologia , Glicosídeos/farmacologia , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Salmonella/efeitos dos fármacos , Taninos/farmacologia , Triterpenos/farmacologia
20.
Life Sci ; 258: 118186, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768586

RESUMO

Antioxidants are essential in preventing the formation and suppressing the activities of reactive nitrogen and oxygen species. The aim of this study was to review the role of antioxidants in cancer development or prevention. Antioxidants are believed to prevent and treat various types of malignancies. Currently, natural antioxidant compounds have been generally consumed to prevent and treat cancers. Certainly, phenolic compounds extracted from medicinal plants have opened a new prospect with respect to the prevention and treatment of cancers due to having antioxidant characteristics. However, some recently published studies have revealed that antioxidant compounds do not indicate absolute anti-tumor properties. Some antioxidants are helpful in cancer initiation and progression. Taken together, antioxidants demonstrate a two-faced nature toward cancer. However, it is required to conduct further cell culture and in vivo studies to confirm the exact role of antioxidants and then use them for efficient cancer treatments.


Assuntos
Antioxidantes/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Metástase Neoplásica , Neoplasias/patologia
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