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1.
Mol Cell ; 79(5): 705-707, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32888435

RESUMO

In this issue of Molecular Cell, Benslimane et al. (2020) perform a CRISPR-Cas9 chemogenomic screen, identifying a network of DNA replication and genome integrity genes with the nutraceutical compound Resveratrol and its analog Pterostilbene, linking these compounds to the induction of DNA replication stress in mammalian cells.


Assuntos
Replicação do DNA , Resveratrol , Animais , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Humanos
2.
Eur Rev Med Pharmacol Sci ; 24(14): 7834-7844, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32744711

RESUMO

The pandemic threat of COVID-19 causes serious concern for people and world organizations. The effect of Coronavirus disease on the lifestyle and economic status of humans is undeniable, and all of the researchers (biologists, pharmacists, physicians, and chemists) can help decrease its destructive effects. The molecular docking approach can provide a fast prediction of the positive influence the targets on the COVID-19 outbreak. In this work, we choose resveratrol (RV) derivatives (22 cases) and two newly released coordinate structures for COVID-19 as receptors [Papain-like Protease of SARS CoV-2 (PBD ID: 6W9C) and 2019-nCoV RNA-dependent RNA Polymerase (PBD ID: 6M71)]. The results show that conformational isomerism is significant and useful parameter for docking results. A wide spectrum of interactions such as Van der Waals, conventional hydrogen bond, Pi-donor hydrogen bond, Pi-Cation, Pi-sigma, Pi-Pi stacked, Amide-Pi stacked and Pi-Alkyl is detected via docking of RV derivatives and COVID-19 receptors. The potential inhibition effect of RV-13 (-184.99 kj/mol), and RV-12 (-173.76 kj/mol) is achieved at maximum value for 6W9C and 6M71, respectively.


Assuntos
Antivirais/metabolismo , Betacoronavirus/metabolismo , Papaína/metabolismo , RNA Replicase/metabolismo , Resveratrol/metabolismo , Vírus da SARS/metabolismo , Proteínas não Estruturais Virais/metabolismo , Antivirais/química , Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , Sítios de Ligação , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Cristalografia por Raios X , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Pandemias , Papaína/química , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Estrutura Terciária de Proteína , RNA Replicase/química , Resveratrol/química , Resveratrol/uso terapêutico , Vírus da SARS/isolamento & purificação , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/virologia , Proteínas não Estruturais Virais/química
3.
Mol Cell ; 79(5): 846-856.e8, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32755594

RESUMO

Resveratrol is a natural product associated with wide-ranging effects in animal and cellular models, including lifespan extension. To identify the genetic target of resveratrol in human cells, we conducted genome-wide CRISPR-Cas9 screens to pinpoint genes that confer sensitivity or resistance to resveratrol. An extensive network of DNA damage response and replicative stress genes exhibited genetic interactions with resveratrol and its analog pterostilbene. These genetic profiles showed similarity to the response to hydroxyurea, an inhibitor of ribonucleotide reductase that causes replicative stress. Resveratrol, pterostilbene, and hydroxyurea caused similar depletion of nucleotide pools, inhibition of replication fork progression, and induction of replicative stress. The ability of resveratrol to inhibit cell proliferation and S phase transit was independent of the histone deacetylase sirtuin 1, which has been implicated in lifespan extension by resveratrol. These results establish that a primary impact of resveratrol on human cell proliferation is the induction of low-level replicative stress.


Assuntos
Proliferação de Células/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Resveratrol/farmacologia , Sistemas CRISPR-Cas , Linhagem Celular , Resistência a Medicamentos/genética , Humanos , Hidroxiureia/farmacologia , Células Jurkat , Nucleotídeos/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Sirtuína 1/metabolismo , Estilbenos/farmacologia
4.
Life Sci ; 258: 118178, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32739468

RESUMO

AIMS: Gentamicin (GEN) is one of the most valuable aminoglycoside antibiotics utilized against life-threatening bacterial infections. Unfortunately, GEN-induced nephrotoxicity limited its clinical utility. The pathologic process of nephrotoxicity caused by GEN may involve epithelial to mesenchymal transition (EMT). Resveratrol (RES) is a natural compound was revealed to inhibit EMT in kidney. The present work was conducted to explore the potential renoprotective role of RES on GEN-induced EMT. Moreover, the underlying signaling pathway of this inhibition was investigated. MAIN METHODS: Mice were treated with GEN by intraperitoneal (i.p.) route daily for 15 days to identify EMT onset with regard to GEN-induced nephrotoxicity. To assess the ameliorative role of RES against GEN-induced EMT, RES was i.p. administrated in high and low doses before and concurrently with GEN treatment. KEY FINDINGS: GEN administration significantly deteriorated kidney functions. In addition, reduced glutathione (GSH) content and catalase (CAT) activity were significantly decreased with a concomitant increase in the content of kidney malondialdehyde (MDA) after GEN treatment. Histological changes and deposition of collagen were extensive in renal corpuscles and tubules. Increased expression of alpha smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1) and phosphorylated (p)-Smad2 were observed after GEN administration, while E-cadherin expression was decreased. On the contrary, pretreatment with both doses of RES reversed the modifications caused by GEN administration. SIGNIFICANCE: We concluded that EMT contributes to pathogenesis of GEN-induced nephrotoxicity. RES has a protective effect on GEN-induced EMT via suppressing oxidative stress and a possible involvement of TGF-ß/Smad signaling pathway.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Gentamicinas/efeitos adversos , Rim/metabolismo , Rim/patologia , Espécies Reativas de Oxigênio/metabolismo , Resveratrol/farmacologia , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Biomarcadores/sangue , Fibrose , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Resveratrol/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
5.
An Acad Bras Cienc ; 92(2): e20191230, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785427

RESUMO

This work evaluated the effect of grape juice, red wine and resveratrol in liver parameters of rats submitted to high-fat diet. Experimental model was conducted with groups of adult females Rattus norvegicus: control (CG); high-fat (HG); grape juice (JG); red wine (RW) and resveratrol solution (RG). The high-fat diet significantly altered hepatocytes and Kupffer cells in all treated groups. HG group presented severe steatosis followed hepatocyte ballooning and tissue damages. JG group minimized hepatic histological lesion caused by high-fat diet and WG group also induced steatosis and inflammation in hepatocytes, similar to HG. Still, resveratrol protected the tissue against fatty liver disease by reducing fat infiltration and inflammation, indicating possible therapeutic effects on the liver. Cell cycle analysis showed that HG promoted damage to the tissue, reducing the viable cell content and increasing apoptosis, even when associated with wine consumption or isolated resveratrol. However, JG protected the liver against cell damage generated by the diet. Consumption of grape juice, even associated with a high-fat diet, represents a promising protection of the liver against cellular damage, but red wine further affects the tissue, and resveratrol alone was able to reduce damage but did not minimize cellular damage to the liver.


Assuntos
Vitis , Vinho , Animais , Dieta Hiperlipídica , Feminino , Sucos de Frutas e Vegetais , Fígado , Ratos , Ratos Wistar , Resveratrol , Estilbenos
6.
Chin J Physiol ; 63(4): 149-155, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32859881

RESUMO

Resveratrol (RSV) has been demonstrated to ameliorate nonalcoholic fatty liver disease (NAFLD) in animal studies. However, RSV was given with the dosage that ranged from 7 to 300 mg/kg body weight (BW). Hence, the study aimed to investigate the efficacy of RSV at a lower dosage on high cholesterol-fructose diet (HCFD)-induced rat model of NAFLD. In the study, male Sprague-Dawley rats were fed with HCFD for 15 weeks. RSV was also given at a daily dose of 1 mg/kg BW for 15 days or 15 weeks by oral delivery. At sacrifice, plasma and liver specimens were acquired for detections of alanine and aspartate aminotransferases, proinflammatory cytokines, and lipid contents. Histological examinations and Western blotting analysis were performed using liver tissues. The results showed that RSV administration reduced plasma levels of aminotransferases and proinflammatory cytokines including interleukin-1 beta (IL-1ß), IL-6, and tumor necrosis factor-alpha (TNF-α) in HCFD-induced NAFLD. RSV also mitigated hepatic lipid accumulation and expression of IL-1ß, IL-6, and TNF-α. Besides, phosphorylation of signal transducer and activator of transcription 3 (STAT3) was reduced with RSV supplementation in the liver of HCFD-fed rats. We concluded that low-dose RSV supplementation attenuated hepatic inflammation and lipid accumulation in HCFD-induced NAFLD. The ameliorative effect of RSV on NAFLD could be associated with downregulation of phosphorylated STAT3.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Dieta Hiperlipídica , Frutose , Inflamação , Lipídeos , Fígado , Masculino , Ratos , Ratos Sprague-Dawley , Resveratrol
7.
Brasília; s.n; 29 jul. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117728

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 16 artigos e 3 protocolos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Avaliação da Tecnologia Biomédica , Midazolam/uso terapêutico , Imunoglobulinas/uso terapêutico , Metilprednisolona/uso terapêutico , Vacinas contra Influenza/uso terapêutico , Propofol/uso terapêutico , Cloroquina/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Fentanila/uso terapêutico , Estudos Transversais , Estudos de Coortes , Enoxaparina/uso terapêutico , Azitromicina/uso terapêutico , Ritonavir/uso terapêutico , Cobre/uso terapêutico , Lopinavir/uso terapêutico , Resveratrol/uso terapêutico , Interferon alfa-2/uso terapêutico , Hidroxicloroquina/uso terapêutico , Ketamina/uso terapêutico
8.
Acta Cir Bras ; 35(5): e202000506, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32638845

RESUMO

PURPOSE: To examine effects of resveratrol on renal ischemia/ reperfusion injury (I/R) in a streptozotocin (STZ)-induced diabetic rat model. METHODS: Twenty-four male Sprague Dawley rats were treated with STZ injection for the development of diabetes, and divided into the following groups: Sham group, I/R group and Resveratrol group (n=8). Resveratrol (RSV) was administered at a dose of 10 mg.kg-1.d-1 fourteen days prior to suffering from I/R. Renal function, histology, SOD, MDA, TUNEL assay and expression of TNF-α, IL-1ß, NF-κB-P65, COX-2 and Caspase3, Bcl2 and Bax were analyzed. RESULTS: Administration of RSV significantly reduced the serum levels of renal dysfunction and injury markers, including creatinine, blood urea nitrogen and MDA; in the other hand, it significantly increased the serum levels of SOD. The protective effect of RSV was also reflected on histologic evaluation. RSV reduced the number of apoptotic cells as determined by TUNEL assay. RSV significantly reduced the protein expression of TNF-α, IL-1ß, NF-κB-P65, COX-2 and Caspase3, and Bax. Meanwhile, RSV significantly increased the protein expression of Bcl2. CONCLUSION: RSV attenuated I/R-induced renal injury in diabetic rats through the modulation of oxidative stress and TNF-α-stimulated inflammation.


Assuntos
Antioxidantes , Diabetes Mellitus Experimental , Traumatismo por Reperfusão , Resveratrol , Animais , Antioxidantes/farmacologia , Inflamação , Rim , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/prevenção & controle , Resveratrol/farmacologia , Fator de Necrose Tumoral alfa
9.
Int J Med Sci ; 17(12): 1803-1810, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32714083

RESUMO

Since the end of 2019, a new type of coronavirus pneumonia (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been spreading rapidly throughout the world. Previously, there were two outbreaks of severe coronavirus caused by different coronaviruses worldwide, namely Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). This article introduced the origin, virological characteristics and epidemiological overview of SARS-CoV-2, reviewed the currently known drugs that may prevent and treat coronavirus, explained the characteristics of the new coronavirus and provided novel information for the prevention and treatment of COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Amidas/farmacologia , Amidas/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , Cloroquina/análogos & derivados , Cloroquina/uso terapêutico , Clorpromazina/uso terapêutico , Coronavirus/genética , Infecções por Coronavirus/genética , Ciclofilinas/antagonistas & inibidores , Desenvolvimento de Medicamentos , Reposicionamento de Medicamentos , Medicamentos de Ervas Chinesas/uso terapêutico , Endocitose/efeitos dos fármacos , Humanos , Soros Imunes , Indutores de Interferon/uso terapêutico , Inibidores da Síntese de Ácido Nucleico/farmacologia , Inibidores da Síntese de Ácido Nucleico/uso terapêutico , Pneumonia Viral/genética , Pirazinas/farmacologia , Pirazinas/uso terapêutico , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Vacinas Virais/uso terapêutico
10.
Sci Total Environ ; 742: 140351, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-32629245

RESUMO

A two-dimensional nanocomposite-based disposable electrochemical sensor was fabricated for the rapid analysis of trans-resveratrol (TRA) in red wine. The sensor was prepared by modifying graphene-molybdenum disulfide (Gr-MoS2) nanocomposite on the surface of screen-printed electrode (SPE). Results show that the Gr-MoS2 nanocomposite with sheet-on-sheet structure can accelerate the oxidation reaction kinetics of TRA due to its large effective electrochemical surface area and high electron transfer rate. As a result, the Gr-MoS2 nanocomposite appears the synergistic effects, making the highly sensitive detection of TRA come true. The prepared sensor showed a linear response in TRA concentration from 1.0 to 200 µmol L-1 (with a limit of detection of 0.45 µmol L-1). After validating the accuracy with high performance liquid chromatography (HPLC), this nanocomposite-based electrochemical sensor can be applied for the detection of TRA in real red wine samples.


Assuntos
Grafite , Nanocompostos , Técnicas Eletroquímicas , Eletrodos , Resveratrol
11.
Cardiovasc Ther ; 2020: 7262474, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32695229

RESUMO

Objectives: Several beneficial effects of resveratrol have already been published. This study evaluated the effect of resveratrol on the hemorheological parameters in patients with heart failure with reduced ejection fraction. Methods: In our double-blind, placebo-controlled human clinical trial, we enrolled 60 outpatients with heart failure. Patients were randomized into two groups: receiving either 100 mg resveratrol capsule daily or placebo for 3 months. Hematocrit was determined by microhematocrit centrifuge. Plasma and whole blood viscosity was evaluated by capillary viscometer. Erythrocyte aggregation was measured by both LORCA and Myrenne aggregometers. LORCA ektacytometer was used for measuring erythrocyte deformability. Exercise capacity was assessed by a 6-minute walk test. Results: Resveratrol treatment did not have any significant effect on hematocrit and viscosity. The erythrocyte deformability also remained unchanged. However, significant improvement of red blood cell aggregation was observed in the resveratrol group compared to baseline after 3 months. Furthermore, positive correlation was found between the exercise capacity and the hemorheological properties (Hct, WBV, and RBC aggregation and deformability) as well. Conclusion: These findings indicate that resveratrol can significantly reduce red blood cell aggregation, which may positively influence microcirculation, which may contribute to the improvement of tissue perfusion and oxygen supply in heart failure.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Agregação Eritrocítica/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Resveratrol/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Fármacos Cardiovasculares/efeitos adversos , Método Duplo-Cego , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Hungria , Masculino , Pessoa de Meia-Idade , Resveratrol/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
12.
Food Chem ; 331: 127264, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32619906

RESUMO

This work aimed to develop a method permitting an informed choice of antioxidants to reduce carcinogenic heterocyclic aromatic amine (HAA) formation during proteinaceous food cooking. Therefore, a three-step approach was developed. First, the most promising antioxidants were selected using molecular modeling approaches. For this, analog design was used to highlight the most suitable antioxidants based on their diversification potential using bioisosteric replacement. Then, structure activity relationship studies allowed drawing the relevant properties for inhibiting HAA formation and explained partly the inhibitory activity. Secondly, the approved antioxidants were tested in ground beef patties to assess their inhibitory properties against HAA formation. Resveratrol was found to be the most efficient as it totally inhibited MeIQ and reduced MeIQx and PhIP formation by 40 and 70%, respectively. Finally, natural ingredients rich in these antioxidants were evaluated. Oregano was found to totally inhibit MeIQ formation and to reduce by half MeIQx and PhIP formation.


Assuntos
Antioxidantes/química , Culinária/métodos , Compostos Heterocíclicos/química , Carne Vermelha , Relação Estrutura-Atividade , Aminas/química , Animais , Bovinos , Modelos Moleculares , Origanum/química , Extratos Vegetais , Quinolinas/química , Quinoxalinas/química , Resveratrol/química , Chá , Vinho
13.
Parasitol Res ; 119(9): 2897-2905, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32677001

RESUMO

The central nervous system of the intermediate host plays a central role in lifelong persistence of Toxoplasma gondii as well as the pathogenesis of congenital toxoplasmosis and reactivated infection in immunocompromised individuals. The purinergic system has been implicated in a wide range of immunological pathways for controlling intracellular responses to pathogens, including T. gondii. In the present study, we investigated the effect of resveratrol (RSV) on ectonucleotidases, adenosine deaminase (ADA), and purinergic receptors during chronic infection by T. gondii. For this study, Swiss mice were divided into control (CTL), resveratrol (RSV), infected (INF), and INF+RSV groups. The animals were orally infected with the VEG strain and treated with RSV (100 mg/kg, orally). Ectonucleotidase activities, P2X7, P2Y1, A1, and A2A purinergic receptor density, ROS, and thiobarbituric acid reactive substances levels were measured in the cerebral cortex of mice. T. gondii infection increased NTPDase and reduced ADA activities. Treatment with RSV also affected enzymes hydrolysing extracellular nucleotides and nucleosides. Finally, RSV affected P1 and P2 purinergic receptor expression during T. gondii infection. Overall, RSV-mediated beneficial changes in purinergic signalling and oxidative stress, possibly improving cerebral cortex homeostasis in T. gondii infection.


Assuntos
Córtex Cerebral/parasitologia , Inibidores Enzimáticos/farmacologia , Fármacos Neuroprotetores/farmacologia , Resveratrol/farmacologia , Toxoplasmose Animal/tratamento farmacológico , Adenosina Desaminase/metabolismo , Animais , Camundongos , Receptores Purinérgicos/metabolismo , Transdução de Sinais , Toxoplasma/imunologia
14.
AAPS PharmSciTech ; 21(5): 183, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32632576

RESUMO

Pulmonary drug delivery is a noninvasive therapeutic approach that offers many advantages including localized drug delivery and higher patient compliance. As with all formulations, the low aqueous solubility of a drug often poses a challenge in the formulation development. Thus, strategies such as cyclodextrin (CD) complexation have been utilized to overcome this challenge. Resveratrol (RES), a natural stilbene, has shown abundant anti-cancer properties. Due to many drawbacks of conventional chemotherapeutics, RES has been proposed as an emerging alternative with promising pharmacological effects. However, RES has limited therapeutic applications due to low water solubility, chemical stability, and bioavailability. This study was aimed at developing an inhalable therapy that would increase the aqueous solubility and stability of RES by complexation with sulfobutylether-ß-cyclodextrin (SBECD). Phase solubility profiles indicated an optimal stoichiometric inclusion complex at 1:1 (SBECD:RES) ratio for formulation considerations. Physiochemical characterizations were performed to analyze CD-RES. Stability studies at pH 7.4 and in plasma indicated significant improvement in RES stability after complexation, with a much longer half-life. The mass median aerodynamic diameter (MMAD) of CD-RES was 2.6 ± 0.7 µm and fine particle fraction (FPF) of 83.4 ± 3.0% are suitable for pulmonary delivery and efficient deposition. Lung cancer was selected as the respiratory model disease, owing to its high relevance as the major cause of cancer deaths worldwide. Cell viability studies in 5 non-small-cell-lung-cancer (NSCLC) cell lines suggest CD-RES retained significant cytotoxic potential of RES. Taken together, CD-RES proves to be a promising inhalation treatment for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ciclodextrinas/química , Neoplasias Pulmonares/tratamento farmacológico , Resveratrol/administração & dosagem , Administração por Inalação , Disponibilidade Biológica , Portadores de Fármacos/metabolismo , Estabilidade de Medicamentos , Humanos , Pulmão/metabolismo , Solubilidade
15.
Int. j. morphol ; 38(3): 558-564, June 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1098287

RESUMO

Chronic hepatotoxicity is a debilitating and frequently life-threatening disease resulting in progressive liver failure. The toxic chemical, thioacetamide (TAA) is used to evaluate hepatoprotective agents, and the polyphenolic compound, resveratrol was proposed as a novel treatment for diseases with hyperactivation of the mammalian target of rapamycin (mTOR) cell signaling pathway. This analysis sought to investigate the potential protective effect of resveratrol against liver injury induced by TAA via the inhibition of hepatic mTOR. Model group rats received several injections of TAA (200 mg/kg; twice a week for 8 weeks) before being sacrificed at week 10 and the protective group was pretreated with resveratrol (20 mg/kg) daily for two weeks prior to TAA injections and continued receiving both agents until the end of the experiment. Harvested liver tissues were examined using light microscopy and liver homogenates were assayed for biomarkers of inflammation and assessed the levels of mTOR protein in all animal groups. In addition, blood samples were assayed for biomarkers of liver injury enzyme. TAA substantially damaged the hepatic tissue of the model group such as infiltration of inflammatory cells, vacuolated cytoplasm, dark pyknotic nuclei, and dilated congested blood vessel that were effectively protected by resveratrol. Resveratrol also significantly (p<0.05) inhibited TAA-induced mTOR, high sensitivity c-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in harvested liver homogenates and blood samples. Thus, we conclude that resveratrol effectively protects against TAA-induced hepatotoxicity in rats, possibly due to the inhibition of mTOR and inflammation.


La hepatotoxicidad crónica es una enfermedad debilitante y potencialmente mortal que produce insuficiencia hepática progresiva. La toxicidad del químico de la tioacetamida (TAA) se utiliza para evaluar los agentes hepatoprotectores y el compuesto polifenólico, resveratrol, se propuso como un nuevo tratamiento para enfermedades con hiperactivación de la vía de señalización celular mTOR (mammalian Target of Rapamycin). Aquí buscamos investigar el posible efecto protector del resveratrol contra la lesión hepática inducida por TAA a través de la inhibición de la vía de señalización mTOR en hepatocitos. Las ratas del grupo modelo recibieron varias inyecciones de TAA (200 mg / kg; dos veces por semana durante 8 semanas) antes de ser sacrificadas en la semana 10 y el grupo protector se trató previamente con resveratrol (20 mg / kg) diariamente durante dos semanas antes de las inyecciones de TAA y continuó recibiendo ambos agentes hasta el final del experimento. Se examinaron los tejidos hepáticos recolectados usando microscopía óptica y se analizaron los homogeneizados hepáticos para detectar biomarcadores de inflamación y se evaluaron los niveles de proteína mTOR en todos los grupos de animales. Además, se analizaron muestras de sangre para detectar biomarcadores de la enzima de lesión hepática. TAA dañó sustancialmente el tejido hepático del grupo modelo, con infiltración de células inflamatorias, citoplasma vacuolado, núcleos picnóticos oscuros y vasos sanguíneos congestionados dilatados que estaban efectivamente protegidos por el resveratrol. El resveratrol también inhibió significativamente (p <0.05) mTOR, proteína C-reactiva (hs-CRP), factor de necrosis tumoral alfa (TNF-α), interleucina-6 (IL-6), alanina aminotransferasa (ALT ) y aspartato aminotransferasa (AST) en las muestras de sangre y de hígados recolectados. En conclusión, el resveratrol protege eficazmente contra la hepatotoxicidad inducida por TAA en ratas, posiblemente debido a la inhibición de mTOR y de la inflamación.


Assuntos
Animais , Masculino , Camundongos , Tioacetamida/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Resveratrol/administração & dosagem , Aspartato Aminotransferases/análise , Proteína C-Reativa/análise , Fator de Necrose Tumoral alfa/análise , Alanina Transaminase/análise , Modelos Animais de Doenças
16.
Int. j. morphol ; 38(3): 585-591, June 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1098291

RESUMO

Acetaminophen (also called paracetamol, or APAP) induced nephrotoxicity is reported after accidental or intentional ingestion of an overdose of the drug. Renal tubular ultrastructural alterations induced by APAP overdose associated with the induction of biomarkers of kidney injury have not been investigated before. Also, we investigated whether the combined polyphenolic anti-inflammatory and antioxidants agents, resveratrol (RES) and quercetin (QUR) can protect against APAP-induced acute kidney injury. The model group of rats received a single dose of APAP (2 g/kg), whereas the protective group of rats was pre-treated for 7 days with combined doses of RES (30 mg/kg) and QUR (50 mg/kg) before being given a single dose of APAP. All rats were then sacrificed one day post APAP ingestion. Harvested kidney tissues were prepared for transmission electron microscopy (TEM) staining and blood samples were assayed for urea, creatinine, and biomarkers of inflammation and oxidative stress. TEM images and blood chemistry analysis showed that APAP overdose induced kidney damage as demonstrated by substantial alterations to the proximal convoluted tubule ultrastructure, and a significant (p<0.05) increase in urea, creatinine, tumor necrosis factor-alpha (TNF-a), and malondialdehyde (MDA) blood levels, which were protected by RES+QUR. These findings indicate that APAP induces alterations to the renal tubular ultrastructure, which is inhibited by resveratrol plus quercetin, which also decreases blood levels of kidney injury biomarkers.


El objetivo de este trabajo fue estudiar la nefrotoxicidad inducida por acetaminofeno (también llamado paracetamol o APAP) después de la ingestión accidental o intencional de una sobredosis de la droga. Las alteraciones ultraestructurales tubulares renales inducidas por sobredosis de APAP asociadas con la inducción de biomarcadores de daño renal no se han investigado. Además, estudiamos si los agentes combinados antiinflamatorios y antioxidantes polifenólicos, el resveratrol (RES) y la quercetina (QUR) pueden proteger contra la lesión renal aguda inducida por APAP. El grupo modelo de ratas recibió una dosis única de APAP (2 g / kg), mientras que el grupo protector de ratas se trató previamente durante 7 días con dosis combinadas de RES (30 mg / kg) y QUR (50 mg / kg) antes de recibir una dosis única de APAP. Todas las ratas se sacrificaron un día después de la ingestión de APAP. Los tejidos renales fueron preparados para el análisis a través de la microscopía electrónica de transmisión (MET). En las muestras de sangre se determinaron la urea, creatinina y los biomarcadores de inflamación y estrés oxidativo. Las imágenes MET y el análisis químico de la sangre mostraron que la sobredosis de APAP inducía daño renal, como lo demuestran las alteraciones sustanciales en la ultraestructura del túbulo contorneado proximal, y además, de un aumento significativo (p <0,05) de la urea, creatinina, factor de necrosis tumoral alfa y niveles sanguíneos de malondialdehído, protegidos por RES + QUR. Estos hallazgos indican que APAP induce alteraciones en la ultraestructura tubular renal, inhibida por el resveratrol más quercetina, que también disminuye los niveles sanguíneos de biomarcadores de daño renal.


Assuntos
Animais , Ratos , Quercetina/administração & dosagem , Resveratrol/administração & dosagem , Túbulos Renais/efeitos dos fármacos , Acetaminofen/toxicidade , Quercetina/farmacologia , Ureia/sangue , Ratos Sprague-Dawley , Creatinina/sangue , Microscopia Eletrônica de Transmissão , Modelos Animais de Doenças , Overdose de Drogas , Resveratrol/farmacologia , Túbulos Renais/patologia , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem
17.
Nat Commun ; 11(1): 2814, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32499508

RESUMO

Food consumption is fundamental for life, and eating disorders often result in devastating or life-threatening conditions. Anorexia nervosa (AN) is characterized by a persistent restriction of energy intake, leading to lowered body weight, constant fear of gaining weight, and psychological disturbances of body perception. Herein, we demonstrate that SIRT1 inhibition, both genetically and pharmacologically, delays the onset and progression of AN behaviors in activity-based anorexia (ABA) models, while SIRT1 activation accelerates ABA phenotypes. Mechanistically, we suggest that SIRT1 promotes progression of ABA, in part through its interaction with NRF1, leading to suppression of a NMDA receptor subunit Grin2A. Our results suggest that AN may arise from pathological positive feedback loops: voluntary food restriction activates SIRT1, promoting anxiety, hyperactivity, and addiction to starvation, exacerbating the dieting and exercising, thus further activating SIRT1. We propose SIRT1 inhibition can break this cycle and provide a potential therapy for individuals suffering from AN.


Assuntos
Anorexia Nervosa/metabolismo , Regulação da Expressão Gênica , Fator 1 Nuclear Respiratório/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Sirtuína 1/metabolismo , Animais , Peso Corporal , Carbazóis/farmacologia , Modelos Animais de Doenças , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/metabolismo , Fenótipo , Resveratrol/farmacologia , Estresse Mecânico , Regulação para Cima
18.
J Asian Nat Prod Res ; 22(10): 947-955, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32567953

RESUMO

A new approach for the total synthesis of the active stilbene dimer dehydro-δ-viniferin has been achieved in 9 steps with methyl 4-hydroxybenzoate and 3,5-dihydroxyacetophenone as starting materials. The key feature of the method is the amberlyst 15-mediated cyclodehydration of α-aryloxyketone. [Formula: see text].


Assuntos
Benzofuranos , Estilbenos , Estrutura Molecular , Resorcinóis , Resveratrol
19.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(1): 85-89, 2020 Jan 28.
Artigo em Chinês | MEDLINE | ID: mdl-32476378

RESUMO

OBJECTIVE: To observe the effects of resveratrol on body composition in adult catch-up growth rats and to explore the possible mechanism. METHODS: Eight-week-old male SD rats were randomly divided into 6 groups: normal controls for 4 weeks (NC4) group, caloric restriction for 4 weeks (R4) group, calorie restriction meanwhile resveratrol treatment for 4 weeks (R4E) group, normal controls for 12 weeks (NC12) group, catch-up growth (CUG) group and catch-up growth meanwhile resveratrol treatment for 8 weeks (CUGE) group. At the end of the four-week and twelve-week experimental period, the body weight, muscle and fat content of trunk and whole body, the ratio of trunk to whole body fat were detected, and at the end of twelve-week experimental period, the expression of SIRT1 in skeletal muscle and epididymal adipose tissue, and the expression of PPARγ in epididymal adipose tissue were detected. RESULTS: Compared with NC12 group, the fat content of trunk and whole body and trunk to whole body fat ratio in CUG group were increased significantly, along with the expression of PPARγ in epididymal adipose tissue was increased significantly (P<0.05), while the muscle content of trunk and whole body, the expression of SIRT1 in skeletal muscle and epididymal adipose tissue in CUG group were decreased significantly compared with NC12 group (P<0.05 or P<0.01); compared with CUG group, oral administration of resveratrol distinctly reduced the body fat content and trunk to whole body fat ratio in the CUGE groups, and the expression of PPARγ in epididymal adipose tissue of CUGE group was also significantly decreased (P<0.05). Meanwhile, the muscle content and the expression of SIRT1 in skeletal muscle and epididymal adipose tissue in CUGE group were significantly increased compared with the CUG group (P<0.05). CONCLUSION: Resveratrol can decrease body fat content, increase muscle content and improve abdominal fat accumulation in adult catch-up growth rats, and its mechanism may be associated with increasing SIRT1 expression in skeletal muscle and visceral adipose tissue, decreasing PPARγ expression in visceral adipose tissue.


Assuntos
Composição Corporal/efeitos dos fármacos , Resveratrol/farmacologia , Tecido Adiposo , Animais , Restrição Calórica , Gordura Intra-Abdominal , Masculino , Músculo Esquelético , PPAR gama/metabolismo , Ratos , Ratos Sprague-Dawley , Sirtuína 1/metabolismo
20.
Int Endod J ; 53(9): 1253-1263, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32515014

RESUMO

AIM: To evaluate in a laboratory setting the response of human mesenchymal stem cells (MSCs) to pulp-capping materials with and without resveratrol (RSV). METHODOLOGY: Five materials, Calcimol LC, Life, TheraCal LC, ProRoot MTA and Biodentine, were prepared according to the manufacturers' instructions. Human MSCs were then exposed to these materials, with and without RSV, for 24 h (n = 8). Cell viability was evaluated using the MTT assay, and total cell death was quantified by annexin V-FITC staining with flow cytometry. The expression levels of the IL-8, IL-10, HBD-2 and BCL-2 genes were investigated using real-time polymerase chain reaction (RT-PCR). Data obtained from MTT test were analysed using one-way anova, and Tukey's multiple-comparison test. The paired Student t test was employed to compare the effects of materials on gene expression (significance level of 5%). RESULTS: The group cell viabilities were Calcimol LC 53%, Life 43%, TheraCal LC 78%, ProRoot MTA 75% and Biodentine 78%. Calcimol LC and Life exhibited significant differences compared with the control groups (P < 0.05). The percentages of necrotic/late apoptotic cells associated with Calcimol LC and TheraCal LC were greater than in the other materials. However, when RSV was added to wells containing materials, cell viability increased to Calcimol LC 63%, Life 52%, TheraCal LC 82%, ProRoot MTA 91% and Biodentine 96%, and the percentages of early apoptotic and late apoptotic/necrotic cells decreased. Calcimol LC + RSV and Life + RSV differed significantly from the control group (P < 0.05). The expression of IL-8 gene was high for all materials, ProRoot MTA caused significant overexpression, and the addition of RSV reduced the expression of IL-8 in the Calcimol LC, TheraCal LC and ProRoot MTA groups and led to increased expression of IL-10 in the Calcimol LC, Life and Biodentine groups. HBD-2 and BCL-2 exhibited increased expression in ProRoot MTA with RSV (P < 0.05). CONCLUSIONS: The addition of RSV exerted a protective effect on MSCs and regulated the inflammatory process by altering the expression levels of pro- and anti-inflammatory genes.


Assuntos
Agentes de Capeamento da Polpa Dentária e Pulpectomia , Resveratrol , Compostos de Alumínio , Compostos de Cálcio , Capeamento da Polpa Dentária , Combinação de Medicamentos , Humanos , Óxidos , Silicatos , Células-Tronco
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