Navegando por Autor "Oliveira, Daiane Teixeira de"
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Item Antitumoral activity of micellar solutions containing allyl isothiocyanate : an in vitro study.(2021) Almeida, Tamires Cunha; Oliveira, Daiane Teixeira de; Sávio, André Luiz Ventura; Perasoli, Fernanda Barçante; Silva, Glenda Nicioli da; Barichello, José MarioIntroduction: Several natural products exhibit promising antineoplastic activity against bladder cancer cells, including allyl isothiocyanate (AITC). However, the AITC irritates the mucous membranes and induces eczematous or vesicular skin reactions. Thus, pharmaceutical formulations are necessary to overcome these problems. The aim was to develop micellar solutions containing AITC and investigate their antitumoral activity in bladder carcinoma cell lines. Method: The micellar solutions were prepared by cold dispersion method. Subsequently, we evaluated cytotoxicity, cell proliferation, cell cycle kinetics and long-term effects of micelles in bladder cancer cells. Results: Cytotoxicity and cell proliferation assays showed there was an increase in AITC activity when it was encapsulated in micelles. We also observed cell cycle arrest in the S phase after treatment with AITC-micelles. Furthermore, the formulation was able to maintain the long-term effects of free AITC. Conclusions: The micellar solutions developed can become an interesting approach for administration of AITC in the treatment of bladder cancer.Item Bases moleculares e bioquímicas da patogênese da doença hepática gordurosa não alcoólica induzida por carboidratos simples : foco na reprogramação epigenética e no metabolismo lipídico hepático.(2020) Oliveira, Daiane Teixeira de; Cota, Renata Guerra de Sá; Cota, Renata Guerra de Sá; Rodrigues, Tiago; Coimbra, Cândido Celso; Bezerra, Frank Silva; Isoldi, Mauro CésarEsse estudo teve como objetivo fornecer uma visão abrangente dos eventos metabólicos e bioquímicos que envolvem o consumo de carboidratos simples, em condição de equivalência energética, bem como elucidar o papel do metabolismo lipídico e das modificações epigenéticas na patogênese da doença hepática gordurosa não alcoólica (DHGNA). Por razões didáticas, dividimos os resultados desse estudo em três capítulos, de acordo com os objetivos específicos estabelecidos. No capítulo I e II avaliamos o efeito do consumo crônico de carboidratos simples sobre o desenvolvimento de alterações metabólicas e o papel do metabolismo lipídico hepático sobre o desenvolvimento de alterações hepatocelulares, respectivamente. Para isso, ratos Wistar recém-desmamados foram submetidos à dieta controle (DC; n=8) ou a uma dieta isocalórica rica em carboidratos simples (DRCS; n=12), ad libitum por 18 semanas. Capítulo I: independentemente do consumo calórico positivo a DRCS levou ao aumento significativo da massa corporal e da massa gorda, do índice de adiposidade, do índice de Lee, da massa do fígado, do nível sérico de triacilglicerol e VLDL, do conteúdo lipídico hepático, da frequência cardíaca e à hiperplasia e hipertrofia do tecido adiposo retroperitoneal, induziu intolerância à glicose, resistência à insulina e aumento compensatório da secreção de insulina pelas células β pancreáticas. Capítulo II: no fígado a DRCS desencadeou o estresse oxidativo e danos teciduais graves, como esteatose microvesicular, morte celular e ballooning. Através da análise do lipidoma hepático foram identificados e quantificados 362 espécies moleculares de lipídios. Mais especificamente, ratos alimentados com a DRCS exibiram aumento do conteúdo hepático de triacilglicerol esterificado em ácidos graxos saturados e monossaturados, aumento de lipídios biomarcadores de disfunção mitocondrial (fosfatidilglicerol, cardiolipina e ubiquinona) e do comprometimento da βoxidação de ácidos graxos (acilcarnitina) e alterações em lipídios de membrana. A DRCS também levou a down-regulation de genes da oxidação de ácidos graxos no fígado. No capítulo III avaliamos o efeito temporal da DRCS sobre a indução da reprogramação epigenética no fígado. Para isso, ratos Wistar recém-desmamados foram divididos nos grupos experimentais DC (n=20) e DRCS (n=20) e submetidos as respectivas dietas pelo período de 4 (n=5), 8 (n=5), 15 (n=5) e 18 (n=5) semanas. O desenvolvimento e a progressão da DHGNA, induzido pela DRCS, foi acompanhado pela desregulação dos padrões epigenéticos, evidenciados pela modulação negativa da expressão das metilases (Dnmts) e desmetilase (Tet2) do DNA, e das sirtuínas (sirt1-7), pela diminuição da metilação global do DNA e pela modulação negativa da marca de repressão da transcrição (H3K9me3 e H3K27me3) induzida pelo envelhecimento. Em conclusão, esses achados sugerem que o consumo precoce e crônico da DRCS leva ao fenótipo da síndrome metabólica, independentemente da ingestão calórica. No fígado, a DRCS induz a sobrecarga e o comprometimento da β-oxidação de ácidos graxos e desencadeia a reprogramação epigenética, resultando em perturbações drásticas no metabolismo lipídico hepático e no desenvolvimento e progressão da DHGNA. Esses achados contribuem para a consolidação do efeito deletério da DRCS sobre a saúde e para a elucidação das vias moleculares da patogênese da DHGNA.Item Cytotoxic and toxicogenomic effects of silibinin in bladder cancer cells with different TP53 status.(2017) Oliveira, Daiane Teixeira de; Sávio, André Luiz Ventura; Marcondes, João Paulo de Castro; Barros, Tatiane Martins Barcelos; Barbosa, Ludmila Correia; Salvadori, Daisy Maria Fávero; Silva, Glenda Nicioli daSilibinin is a natural phenol found in the seeds of the milk thistle plant. Recent data have shown its effectiveness for preventing/treating bladder tumours. Therefore, in this study we investigated the cytotoxic and toxicogenetic activity of silibinin in bladder cancer cells with different TP53 statuses. Two bladder urothelial carcinoma cell lines were used: RT4 (wild-type TP53 gene) and T24 (mutated TP53 gene). Cell proliferation, clonogenic survival, apoptosis rates, genotoxicity and relative expression profile of FRAP/mTOR, FGFR3, AKT2 and DNMT1 genes and of miR100 and miR203 were evaluated. Silibinin promoted decreased proliferation and increased late apoptosis in TP53 mutated cells. Increased early apoptosis rates, primary DNA damage, and decrease of cell colonies in the clonogenic survival assay were detected in both RT4 and T24 cell lines. Down-regulation of FRAP/mTOR, AKT2, FGFR3, DNMT1 and miR100 expression occurred in RT4 cells. Modulation of miR203 was observed in both cell lines. In conclusion, despite the reduction of clone formation in both cell lines, the toxicogenomic effect of silibinin on FRAP/mTOR, AKT2, FGFR3, DNMT1 and miR100 was dependent on the TP53 status. Taken together, the data confirmed the role of silibinin as an antiproliferative compound, whose mechanism of action was related to the TP53 status.Item Dynamic changes in hepatic DNA methylation during the development of nonalcoholic fatty liver disease induced by a high‐sugar diet.(2022) Oliveira, Daiane Teixeira de; Paiva, Nívia Carolina Nogueira de; Carneiro, Cláudia Martins; Cota, Renata Guerra de SáDNA methylation is an important epigenetic mechanism of gene expression control. The present study aimed to evaluate the temporal efect of isocaloric high-sugar diet (HSD) intake on the development of nonalcoholic fatty liver disease (NAFLD) and the role of DNA methylation in this event. Newly weaned Wistar rats were divided into eight groups and fed a standard chow diet or an HSD ad libitum for 4 weeks, 8 weeks, 15 weeks, and 18 weeks. After the experimental periods, the animals were euthanized and their livers were removed for histological analysis, gene expression of maintenance methylase (Dnmt1), de novo methylases (Dnmt3a and Dnmt3b), demethylases (Tet2 and Tet3) of DNA, and global DNA methylation. HSD intake led to the gradual development of NAFLD. HSD intake for 18 weeks was associated with downregulation of Dnmt1 expression and global DNA hypomethylation; these results were negatively correlated with more severe steatosis scores observed in these animals. The HSD consumption for 18 weeks was also associated with a decrease in Dnmt3a and Tet2 expression. Interestingly, the expression of de novo methyltransferase Dnmt3b was reduced by HSD during all experimental periods. Together, these results indicate that the downregulation of de novo DNA methylation, Dnmt3b, induced by HSD is the primary factor in the develop- ment of NAFLD. On the other hand, disease progression is associated with downregulation of maintenance DNA methylation and global DNA hypomethylation. These results suggest a link between the dynamic changes in hepatic DNA methylation and the development of NAFLD induced by an HSD intake.Item Efeitos toxicogenéticos e toxicogenômicos do composto Silibinina em linhagens celulares de carcinoma de bexiga.(2016) Oliveira, Daiane Teixeira de; Silva, Glenda Nicioli da; Marcondes, João Paulo de Castro; Lima, Angélica Alves; Spanó, Mário AntônioA Silibinina é um flavonoide de ocorrência natural, isolado a partir dos frutos e sementes do Cardo-mariano (Silybum marianum). Dados recentes têm demonstrado a eficácia deste fitoquímico na prevenção e tratamento de tumores da bexiga (in vitro e in vivo), tornando-o um agente antineoplásico promissor. Mutações no gene TP53 são as alterações mais comuns em células de câncer de bexiga e estão relacionadas à resposta ao tratamento. Assim, o presente estudo objetivou avaliar o potencial antineoplásico e os possíveis mecanismos de ação da silibinina em células uroteliais de carcinoma de bexiga com diferentes status do gene TP53 (RT4 - tumor de baixo grau, com gene TP53 selvagem; T24 - tumor de alto grau, com gene TP53 mutado). As células foram tratadas com diferentes concentrações de silibinina para os ensaios de citotoxicidade, sobrevivência celular e clonogênica, para o teste do cometa, para os experimentos de ciclo celular e apoptose e para a análise da expressão dos genes RASSF1 e HDAC1. Os resultados mostraram aumento de danos primários no DNA para ambas as linhagens celulares. Além disso, diminuição da taxa de proliferação celular após 48 horas de tratamento em células TP53 mutado, mas não em células do tipo selvagem, foi observada. No entanto, após 72 horas de tratamento com a silibinina, diminuição da proliferação celular em ambas as linhagens celulares foi demonstrada. No teste de sobrevivência clonogênica, a silibinina induziu a diminuição significativa da capacidade de formação de colônias em T24 e RT4 células. Aumento das taxas de apoptose iniciais foram observados em ambas as linhagens celulares enquanto as taxas de apoptose tardia só foram detectadas na linhagem T24. Alterações na cinética do ciclo celular não foram observadas. Da mesma maneira, alterações na expressão dos genes RASSF1 e HDAC1 não foram detectadas. Em conclusão, a silibinina promoveu a diminuição da capacidade proliferativa em linhagens celulares de carcinoma urotelial de bexiga por meio da indução de danos na molécula de DNA e ativação de mecanismos de morte celular independentes do status de TP53. Esses resultados fornecem informações relevantes que poderão contribuir na elucidação dos mecanismos de ação da silibinina no tratamento do câncer de bexiga.Item High-sugar diet intake, physical activity, and gut microbiota crosstalk : implications for obesity in rats.(2020) Neves, Viviano Gomes de Oliveira; Oliveira, Daiane Teixeira de; Oliveira, Deborah Campos; Perucci, Luiza Oliveira; Santos, Talita Adriana Pereira dos; Fernandes, Isabela da Costa; Sousa, Graziele Galdino de; Barboza, Natália Rocha; Cota, Renata Guerra de SáThis study aims to evaluate the effect of long-term high-sugar diet (HSD) intake and regular physical activity on gut microbiota as well as its health impact. Weaned male Wistar rats were fed with standard chow diet (SSD) or HSD ad libitum and subjected or not to regular swimming training with a workload (2% of body weight) for 15 weeks. Feces samples were used on microbiome analysis using 16S rRNA amplicon sequencing. HSD increased body mass, adipose cushions, and the serum levels of triglycerides and VLDL, also changed the bacteria taxons associated with metabolic disorders (increase taxons belonging to Proteobacteria phylum and decrease Pediococcus genus); the swim training reverted these changes. SSD intake increased the abundance of bacteria associated with metabolization of dietary fiber. Training in association with SSD consumption beneficially modulated the microbiota, increasing the Bacteroidetes, Bacteroidaceae, Porphyromonadaceae, Parabacteroides, and Lactobacillaceae, and decreasing the Firmicute/Bacteroidetes ratio; training was not able to maintain this profile in animals SHD-fed. Physical training modulates the gut microbiota reversing the obesogenic response caused by SHD. However, training itself is not efficient for up-regulating the probiotic bacteria in comparison to its association with a balanced diet.Item High-sugar diet leads to obesity and metabolic diseases in ad libitum-fed rats irrespective of caloric intake.(2020) Oliveira, Daiane Teixeira de; Fernandes, Isabela da Costa; Sousa, Graziele Galdino de; Santos, Talita Adriana Pereira dos; Paiva, Nívia Carolina Nogueira de; Carneiro, Cláudia Martins; Evangelista, Elísio Alberto; Barboza, Natália Rocha; Cota, Renata Guerra de SáObjective: Provide a comprehensive view of the events surrounding the sugar consumption, under conditions of energy equivalence; through the analysis of behavioral aspects of intake, and of biochemical, metabolic and physiological parameters, as well as the effect of this nutrient on the plasticity of adipose tissue. Materials and methods: Newly weaned male Wistar rats were classified in two groups and subjected to the following normocaloric diets: standard chow diet or to high-sugar diet (HSD) ad libitum for 18 weeks. Results: The animals submitted to the HSD were associated with a lower caloric intake during the 18 weeks of experimentation. However, the HSD induced a significant increase in body weight, white adipose tissue weight, adiposity index, Lee index, and the levels of triglycerides and very low-density lipoprotein in the serum. In addition, it induced glucose intolerance, insulin resistance and compensatory increase of insulin secretion by pancreatic β-cells. Also increased heart rate and induced hyperplasia, and hypertrophy of retroperitoneal visceral adipose tissue. In the liver, the HSD was associated with increased hepatic lipid content (i.e., triglycerides and cholesterol) and hepatomegaly. Conclusion: The post-weaning consumption of HSD induces an adaptive response in metabolism; however, such an event is not enough to reverse the homeostatic imbalance triggered by the chronic consumption of this macronutrient, leading to the development of metabolic syndrome, irrespective of caloric intake. These findings corroborate recent evidence indicating that sugar is a direct contributor to metabolic diseases independent of a positive energy balance.Item Liver lipidome signature and metabolic pathways in nonalcoholic fatty liver disease induced by a high-sugar diet.(2021) Oliveira, Daiane Teixeira de; Chaves Filho, Adriano de Britto; Yoshinaga, Marcos Yukio; Paiva, Nívia Carolina Nogueira de; Carneiro, Cláudia Martins; Miyamoto, Sayuri; Festuccia, William Tadeu Lara; Cota, Renata Guerra de SáDietary sugar is an important determinant of the development and progression of nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanisms underlying the deleterious effects of sugar intake on NAFLD under energy-balanced conditions are still poorly understood. Here, we provide a comprehensive analysis of the liver lipidome and mechanistic insights into the pathogenesis of NAFLD induced by the chronic consumption of high-sugar diet (HSD). Newly weaned male Wistar rats were fed either a standard chow diet or an isocaloric HSD for 18 weeks. Livers were harvested for histological, oxidative stress, gene expression, and lipidomic analyses. Intake of HSD increased oxidative stress and induced severe liver injury, microvesicular steatosis, and ballooning degeneration of hepatocytes. Using untargeted lipidomics, we identified and quantified 362 lipid species in the liver. Rats fed with HSD displayed increased hepatic levels of triacylglycerol enriched in saturated and monounsaturated fatty acids, lipids related to mitochondrial function/structure (phosphatidylglycerol, cardiolipin, and ubiquinone), and acylcarnitine (an intermediate lipid of fatty acid beta-oxidation). HSD-fed animals also presented increased levels of some species of membrane lipids and a decreased content of phospholipids containing omega-6 fatty acids. These changes in the lipidome were associated with the downregulation of genes involved in fatty acid oxidation in the liver. In conclusion, our data suggest that the chronic intake of a HSD, even under isocaloric conditions, induces lipid overload, and inefficient/impaired fatty acid oxidation in the liver. Such events lead to marked disturbance in hepatic lipid metabolism and the development of NAFLD.Item Uncovering epigenetic landscape : a new path for biomarkers identification and drug development.(2020) Oliveira, Daiane Teixeira de; Cota, Renata Guerra de SáScientifc advances in recent decades have revealed an incredible degree of plasticity in gene expression in response to various environmental, nutritional, physiological, pathological, and behavioral conditions. Epigenetics emerges in this sense, as the link between the internal (genetic) and external (environmental) factors underlying the expression of the phenotype. Methylation of DNA and histone post-translationa modifcations are canonical epigenetic events. Additionally, noncoding RNAs molecules (microRNAs and lncRNAs) have also been proposed as another layer of epigenetic regulation. Together, these events are responsible for regulating gene expression throughout life, controlling cellular fate in both normal and pathological development. Despite being a relatively recent science, epigenetics has been arousing the interest of researchers from diferent segments of the life sciences and the general public. This review highlights the recent advances in the characterization of the epigenetic events and points promising use of these brands for the diagnosis, prognosis, and therapy of diseases. We also present several classes of epigenetic modifying compounds with therapeutic applications (so-call epidrugs) and their current status in clinical trials and approved by the FDA. In summary, hopefully, we provide the reader with theoretical bases for a better understanding of the epigenetic mechanisms and of the promising application of these marks and events in the medical clinic.