Navegando por Autor "Silva, Tales Fernando da"
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Item Antiviral activity of silymarin against Mayaro virus and protective effect in virus-induced oxidative stress.(2018) Camini, Fernanda Caetano; Silva, Tales Fernando da; Caetano, Camila Carla da Silva; Almeida, Letícia Trindade; Ferraz, Ariane Coelho; Vitoreti, Verônica Maria Alves; Silva, Breno de Mello; Silva, Silvana de Queiroz; Magalhães, José Carlos de; Magalhães, Cíntia Lopes de BritoMayaro virus (MAYV) is a neglected arbovirus belonging to the family Togaviridae. Its infection leads to Mayaro fever, with clinical manifestations such as fever, myalgia, headache, rash, arthralgia, vomiting, and diarrhea. The most prominent complaint from infected person is the long-lasting arthritis/arthralgia. The treatment for Mayaro fever is mainly symptom-based and there are no vaccines or antiviral drugs currently available, thus, natural products with anti-MAYV activity may provide a potential alternative. Recent evidences suggest that oxidative stress plays an important role in MAYV infection and compounds capable of modulating oxidative stress could represent a novel therapeutic approach in modulating MAYV-associated oxidative cellular damage. Silymarin is a complex extracted of Silybum marianum, or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. Its antioxidant and antiviral effects, including its antiviral activity against the Chikungunya virus (CHIKV), prompted us to think whether silymarin could also reduce the replication of the MAYV and restore the pro-oxidant/antioxidant balance in the context of MAYV infection, leading to reduced cellular oxidative stress. We assessed the antiviral activity and protective effect of silymarin against oxidative stress in MAYV-infected HepG2 cells. Cytopathic effect inhibition, viral replication, and plaque reduction assays were used to determine the anti-MAYV activity of silymarin. Additionally, we determined whether silymarin could reduce MAYV-induced oxidative cell damage. Briefly, silymarin exhibited potent antiviral activity against MAYV and reduced MAYV-induced ROS formation and levels of malondialdehyde (MDA) and carbonyl protein, which are biomarkers of oxidative stress. In conclusion, the ability of silymarin to inhibit MAYV replication and attenuate MAYV-induce oxidative stress warrants further investigation of this compound as a novel therapeutic approach to Mayaro fever disease.Item Antiviral effect of silymarin against Zika virus in vitro.(2020) Silva, Tales Fernando da; Ferraz, Ariane Coelho; Almeida, Letícia Trindade; Caetano, Camila Carla da Silva; Camini, Fernanda Caetano; Lima, Rafaela Lameira Souza; Andrade, Ana Cláudia dos Santos Pereira; Oliveira, Danilo Bretas de; Rocha, Kamila Lorene Soares; Silva, Breno de Mello; Magalhães, José Carlos de; Magalhães, Cíntia Lopes de BritoZika virus (ZIKV) epidemic and its association with severe neurological syndromes have raised worldwide concern. Despite the great clinical relevance of this infection, no vaccine or specific treatment is available and the search for antiviral compounds against ZIKV is extremely necessary. Several natural compounds, such as silymarin, exhibit antioxidant, hepatoprotective, and antiviral properties; however, the antiviral potential of this compound remains partially investigated. Therefore, the objective of this study was to evaluate in vitro the antiviral activity of silymarin against ZIKV infection. Global antiviral activity, dose-dependent, plaque reduction, and time-of-drug-addition assays were used to determine the anti-ZIKV activity of silymarin. Additionally, to start characterizing the mechanisms of action we determined whether silymarin could have a virucidal effect and inhibit viral adsorption and penetration stages. Regarding its global antiviral activity, silymarin showed significant inhibition of ZIKV infection, protecting cells infected with EC50 equal to 34.17μg/mL, with a selectivity index greater than 17 and 4x greater than that of the positive control (ribavirin). Its greatest efficiency was achieved at 125μg/mL, whose cell viability did not differ from the control without infection and treatment. Furthermore, treatment with silymarin reduced viral load by up to two logs (> 90%) concerning viral control, when evaluating virucidal activity and the precocious times of infection. Thus, our results set to show the promising anti-ZIKV activity of silymarin, which does not seem to have a single inhibition mechanism, acting at different times of infection, and still has the advantage of silymarin be a phytotherapy already available on the market.Item Avaliação in vitro da atividade antiviral da silimarina contra o Zika virus (Flaviviridae).(2018) Silva, Tales Fernando da; Magalhães, Cíntia Lopes de Brito; Costa, Daniela Caldeira; Ferreira, Jaqueline Maria Siqueira; Magalhães, Cíntia Lopes de BritoO Zika virus (ZIKV) é um arbovírus pertencente à família Flaviviridae e ao gênero Flavivirus. Em humanos, causa a febre Zika, uma doença com sintomas tais como febre, mialgia e cefaleia. Ainda, a infecção pelo ZIKV é relacionada a casos de microcefalia e síndrome de Guillain-Barré no Brasil. Até o momento, não há vacina licenciada e/ou tratamento específico para a febre Zika, portanto, a busca por compostos com atividade antiviral pode ser uma alternativa promissora para o tratamento da doença. Neste contexto, existem muitos compostos naturais capazes de gerar benefícios saudáveis, e a silimarina, um conjunto de flavonoides extraído da planta cardo de leite (Silybum marianum), se destaca pelas suas propriedades antioxidante, hepatoprotetora e antiviral. Assim, o principal objetivo desse trabalho foi avaliar a atividade antiviral in vitro da silimarina contra o ZIKV. A citotoxicidade da silimarina e sua atividade antiviral contra o ZIKV foram testados em células Vero, utilizando diferentes concentrações de silimarina e o ZIKV numa multiplicidade de infecção (moi) de 1. A viabilidade celular e a atividade antiviral global foram avaliadas através do teste de MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). A capacidade da silimarina em reduzir o número de cópias do genoma viral foi também avaliada por qRT-PCR, bem como sua capacidade de inibir a formação das Unidades Formadoras de Placa (UFP). Posteriormente foi avaliada a atividade da silimarina em etapas pré e pós infecção e a capacidade de inativar a partícula viral e inibir as etapas de adsorção e penetração. Para tal, a silimarina foi adicionada às células em diferentes tempos e etapas da infecção viral e, após 24 horas, o sobrenadante foi coletado para determinar o título de vírus por contagem das UFP. A silimarina apresentou CC50 (Concentração Citotóxica para 50% das células) de 247μg/mL, CE50 (Concentração Efetiva para 50% das células) de 19,3μg/mL e IS (Índice de Seletividade) de 12,8, apresentando melhor atividade antiviral na concentração de 100μg/mL. A silimarina reduziu a produção viral em todos os tempos em que foi adicionada, sendo a maior redução observada quando foi feito um pré-tratamento das células, 2 horas antes da infecção. Ainda, a silimarina apresentou efeito virucida e de inibição da penetração e adsorção viral, reduzindo os títulos virais em cerca de duas unidades logarítmicas. Deste modo, é possível concluir que a silimarina possui significante atividade antiviral in vitro contra o ZIKV e, portanto, pode ser um forte candidato para ser utilizado no tratamento das infecções humanas causadas por esse vírus.Item Efects of açai on oxidative stress, ER stress, and infammationrelated parameters in mice with high fat diet-fed induced NAFLD.(2019) Carvalho, Mayara Medeiros de Freitas; Lage, Nara Nunes; Paulino, Alice Helena de Souza; Pereira, Renata Rebeca; Almeida, Letícia Trindade; Silva, Tales Fernando da; Magalhães, Cíntia Lopes de Brito; Lima, Wanderson Geraldo de; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia; Guerra, Joyce Ferreira da CostaNon-alcoholic fatty liver disease (NAFLD), the most predominant liver disease worldwide, is a progressive condition that encompasses a spectrum of disorders ranging from steatosis to steatohepatitis, and, ultimately, cirrhosis and hepatocellular carcinoma. Although the underlying mechanism is complex and multifactorial, several intracellular events leading to its progression have been identified, including oxidative stress, inflammation, mitochondrial dysfunction, apoptosis, and altered endoplasmic reticulum (ER) homeostasis. Phenolic compounds, such as those present in açai (Euterpe oleracea Mart.), are considered promising therapeutic agents due to their possible beneficial effects on the prevention and treatment of NAFLD. We tested in vitro effects of aqueous açai extract (AAE) in HepG2 cells and its influence on oxidative stress, endoplasmic reticulum stress, and inflammation in a murine model of high fat diet-induced NAFLD. In vitro AAE exhibited high antioxidant capacity, high potential to inhibit reactive oxygen species production, and no cytotoxicity. In vivo, AAE administration (3 g/kg) for six weeks attenuated liver damage (alanine aminotransferase levels), inflammatory process (number of inflammatory cells and serum TNFα), and oxidative stress, through the reduction of lipid peroxidation and carbonylation of proteins determined by OxyBlot and modulation of the antioxidant enzymes: glutathione reductase, SOD and catalase. No change was observed in collagen content indicating an absence of fibrosis, stress-related genes in RE, and protein expression of caspase-3, a marker of apoptosis. With these results, we provide evidence that açai exhibits hepatoprotective effects and may prevent the progression of liver damage related to NAFLD by targeting pathways involved in its progression.Item Mayaro virus induction of oxidative stress is associated with liver pathology in a non-lethal mouse model.(2019) Caetano, Camila Carla da Silva; Camini, Fernanda Caetano; Almeida, Letícia Trindade; Ferraz, Ariane Coelho; Silva, Tales Fernando da; Lima, Rafaela Lameira Souza; Carvalho, Mayara Medeiros de Freitas; Castro, Thalles de Freitas; Carneiro, Cláudia Martins; Silva, Breno de Mello; Silva, Silvana de Queiroz; Magalhães, José Carlos de; Magalhães, Cíntia Lopes de BritoMayaro virus (MAYV) causes Mayaro fever in humans, a self-limiting acute disease, with persistent arthralgia and arthritis. Although MAYV has a remerging potential, its pathogenic mechanisms remain unclear. Here, we characterized a model of MAYV infection in 3–4-week BALB/c mice. We investigated whether the liver acts as a site of viral replication and if the infection could cause histopathological alterations and an imbalance in redox homeostasis, culminating with oxidative stress. MAYV-infected mice revealed lower weight gain; however, the disease was self-resolving. High virus titre, neutralizing antibodies, and increased levels of aspartate and alanine aminotransferases were detected in the serum. Infectious viral particles were recovered in the liver of infected animals and the histological examination of liver tissues revealed significant increase in the inflammatory infiltrate. MAYV induced significant oxidative stress in the liver of infected animals, as well as a deregulation of enzymatic antioxidant components. Collectively, this is the first study to report that oxidative stress occurs in MAYV infection in vivo, and that it may be crucial in virus pathogenesis. Future studies are warranted to address the alternative therapeutic strategies for Mayaro fever, such as those based on antioxidant compounds.