Browsing by Author "Araújo, Carolina Morais"
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Item Ação direta da aldosterona em cardiomiócitos de rato.(Programa de Pós-Graduação em Ciências Biológicas. Núcleo de Pesquisas em Ciências Biológicas, Pró-Reitoria de Pesquisa e Pós Graduação, Universidade Federal de Ouro Preto., 2011) Araújo, Carolina Morais; Isoldi, Mauro CésarMuitos estudos têm abordado a via conhecida como não genômica da aldosterona. Estes trabalhos mostram um grande número de atividades fisiológicas desse hormônio, que não envolvem o mecanismo clássico para receptores MR, no qual, ocorre a translocação do complexo hormônio-receptor ao núcleo. Ensaios realizados em culturas primárias de cardiomiócitos de ratos, na presença do inibidor do receptor MR, demonstraram aumento de AMPc e Ca2+ nas células tratadas com aldosterona quando comparados ao seus respectivos controles. O AMPc demonstrou ser modulado também pela presença do Ca2+ intracelular, uma vez que seus níveis decaíram em relação ao controle quando as células foram tratadas com BAPTA-AM (quelante de Ca2+ intracelular). O Ca+2 liberado nesta via provavelmente ativa uma adenilil ciclase sensível ao Ca2+ (AC1 é uma isoforma expressa conhecida nesta linhagem celular) elevando os níveis de AMPc. Os referidos dados também apontam para a ativação de PKC, que diretamente estaria fosforilando ERK5. Outros trabalhos existentes na literatura relataram essa possibilidade apontando como autora uma PKC do tipo ε. Ativação de ERK5 já foi descrita como um dos passos necessários para induzir a célula à hipertrofia. Tais resultados demonstram também, pela primeira vez, a participação da mAKAP no processo hipertrófico gerado pela aldosterona, assim como de um possível “cross talking” entre seus diferentes receptores.Item Análise da eficácia da polpa do fruto e do extrato das folhas de amoreira (Morus nigra l.) sobre a modulação de marcadores metabólicos e marcadores do estado redox celular em um modelo experimental de diabetes tipo 1.(2015) Araújo, Carolina Morais; Costa, Daniela Caldeira; Silva, Marcelo EustáquioDiabetes Mellitus (DM) é uma doença metabólica caracterizada por hiperglicemia crônica e alterações no metabolismo de carboidratos, lipídeos e proteinas. Esta desordem leva a uma diminuição na atividade das enzimas antioxidantes, induz danos às células β-pancreáticas e a elevação da atividade de metaloproteinases de matriz tipo 2 (MMP-2) pelo aumento do estresse oxidativo, prejudicando a produção de insulina e, consequentemente, a manutenção da normoglicemia. A Morus nigra L. possui altas concentrações de metabólitos secundários e, principalmente, possui altas concentrações de fenólicos totais e flavonoides. Com base na composição química da Morus nigra, o seu potencial antioxidante pode ser um fator importante para modular o estresse oxidativo induzido pelo diabetes. Neste contexto, nossa meta principal foi avaliar a eficácia da polpa e do extrato das folhas de amoreira na modulação de parâmetros bioquímicos, atividade de MMP e enzimas antioxidantes em um modelo experimental de diabetes tipo 1. Para tal, este estudo foi subdividido em ensaios in vitro e in vivo. In vitro, objetivou-se caracterizar o perfil fitoquímico e antioxidante da polpa e do extrato das folhas de amoreira. In vivo, objetivamos verificar o potencial hipoglicemiante da polpa e extrato das folhas de amoreira bem como a modulação de parâmetros bioquímicos e enzimas relacionadas ao estresse oxidativo em um modelo experimental de diabetes tipo 1. Os resultados da caracterização fitoquímica sugeriram que a polpa de amora apresenta um conteúdo de flavonoides distinto daqueles encontrados no extrato das folhas. Também, observamos que o extrato das folhas apresentou uma maior quantidade de compostos fenólicos e uma maior capacidade de neutralização do radical DPPH quando comparado à polpa de amora. Para a realização dos ensaios in vivo, 32 ratas Fischer, fêmeas, albinas foram distribuídas em quatro grupos experimentais: controle, diabético, diabético tratado com polpa e diabético tratado com extrato das folhas da amoreira. O DM foi induzido por injeção intraperitoneal de aloxano na concentração de 135 mg/kg. Os animais foram tratados durante 30 dias com a polpa ou extrato das folhas de Morus nigra L.. Ao final do tratamento as ratas foram eutanasiadas e as amostras de fígado e de sangue foram coletadas para as análises de parâmetros bioquímicos e metabólicos. Nossos resultados mostraram que o tratamento de ratas diabéticas com o extrato das folhas diminuiu a hiperglicemia induzida pelo diabetes e aumentou as concentrações séricos de insulina. Este efeito não foi observado no tratamento com a polpa de amora. Além disto, o tratamento com a polpa e extrato das folhas de amora foi responsável pela diminuição na atividade de superóxido dismutase (SOD) e um aumento na atividade de catalase (CAT), restabelecendo a razão SOD/CAT aas concentrações do controle. Observamos também que o tratamento com a polpa e o extrato das folhas de amora diminuiu as concentrações de proteina carbonilada em relação ao grupo diabético não tratado. Em relação às metaloproteinases, não encontramos diferenças significativas na atividade de metaloproteinase de matriz tipo 9 (MMP-9), mas houve uma diminuição na expressão e atividade de MMP-2 em ratas diabéticas tratadas com o extrato das folhas de amora. Estes resultados, analisados em conjunto, sugerem que o extrato das folhas da amoreira é mais eficaz no controle glicêmico e na modulação de MMP-2 do que a polpa de amora em modelo experimental de diabetes tipo 1.Item Anti-Inflammatory and antioxidant properties of black mulberry (Morus nigra L.) in a model of LPS-induced sepsis.(2018) Lúcio, Karine de Pádua; Rabelo, Ana Carolina Silveira; Araújo, Carolina Morais; Brandão, Geraldo Célio; Souza, Gustavo Henrique Bianco de; Silva, Regislainy Gomes da; Souza, Débora Maria Soares de; Silva, André Talvani Pedrosa da; Bezerra, Frank Silva; Calsavara, Allan Jefferson Cruz; Costa, Daniela CaldeiraSepsis is a complex disease and is the cause of many deaths worldwide. Sepsis pathogenesis involves a dysregulated inflammatory response with consequent production of inflammatory mediators and reactive species. The production and excessive release of these substances into the systemic circulation trigger various cellular and metabolic alterations that are observed during the disease evolution. Thus, more studies have been carried out to investigate the therapeutic potential of plants such as Morus nigra L., popularly known as black mulberry. Studies have shown that plants belonging to the Morus genus are rich in secondary metabolites such as flavonoids which are associated with important biological activities as antioxidant and anti-inflammatory actions. Based on this context, the objective of our study was to evaluate the anti-inflammatory and antioxidant properties of Morus nigra L. in a sepsis model induced by LPS. Male C57BL/6 mice were distributed in four groups: control, sepsis, sepsis treated with leaf extract of mulberry, and sepsis treated with mulberry pulp. The animals were treated with 100 μL of their respective treatments for twenty-one days. Sepsis was induced at the 21st day with lipopolysaccharide (LPS) by intraperitoneal injection. The animals were euthanized 24 hours after receiving the LPS injection. The data obtained were analyzed in GraphPad Prism 6.0 software. Our results showed that treatment with either extract significantly decreased the number of leukocytes in the bronchoalveolar lavage fluid and serum levels of TNF in septic animals. Regarding the redox status, the treatments significantly decreased the antioxidant activity of the enzyme glutathione peroxidase. Regarding metalloproteinase type 2, it was observed that the treatment with black mulberry pulp was able to significantly reduce the activity of this enzyme concerning the sepsis group. Finally, these results together promoted an increase in the animal’s survival that received the black mulberry leaf or pulp extract.Item Aqueous extract of Baccharis trimera improves redox status and decreases the severity of alcoholic hepatotoxicity.(2017) Rabelo, Ana Carolina Silveira; Araújo, Glaucy Rodrigues de; Lúcio, Karine de Pádua; Araújo, Carolina Morais; Miranda, Pedro Henrique de Amorim; Silva, Breno de Mello; Carneiro, Ana Cláudia Alvarenga; Ribeiro, Erica Milena de Castro; Lima, Wanderson Geraldo de; Souza, Gustavo Henrique Bianco de; Brandão, Geraldo Célio; Costa, Daniela CaldeiraThe metabolism of ethanol occurs mainly in the liver, promoting increase of reactive oxygen species and nitrogen, leading to redox imbalance. Therefore, antioxidants can be seen as an alternative to reestablish the oxidizing/reducing equilibrium. The aim of this study was to evaluate the antioxidant and hepatoprotective effect of aqueous extract of Baccharis trimera (Less.) DC., Asteraceae, in a model of hepatotoxicity induced by ethanol. The extract was characterized and in vitro tests were conducted in HepG2 cells. It was evaluated the cells viability exposed to aqueous extract for 24 h, ability to scavenging the radical DPPH, besides the production of reactive oxygen species and nitric oxide, and the influence on the transcriptional activity of transcription factor Nrf2 (12 and 24 h) after exposure to 200 mM ethanol. The results showed that aqueous extract was non-cytotoxic in any concentration tested; moreover, it was observed a decrease in ROS and NO production, also promoting the transcriptional activity of Nrf2. In vivo, we pretreatment male rats Fisher with 600 mg/kg of aqueous extract and 1 h later 5 ml/kg of absolute ethanol was administrated. After two days of treatment, the animals were euthanized and lipid profile, hepatic and renal functions, antioxidant status and oxidative damage were evaluated. The treatment with extract improved liver function and lipid profile, reflecting the reduction of lipid microvesicules in the liver. It also promoted an increase of glutathione peroxidase activity, decrease of oxidative damage and MMP2 activity. These results, analyzed together, suggest the hepatoprotective effect of B. trimera aqueous extract.Item Baccharis trimera improves the antioxidant defense system and inhibits iNOS and NADPH oxidase expression in a rat model of inflammation.(2013) Pádua, Bruno da Cruz; Rossoni Júnior, Joamyr Victor; Magalhães, Cíntia Lopes de Brito; Seibert, Janaína Brandão; Araújo, Carolina Morais; Souza, Gustavo Henrique Bianco de; Chaves, Míriam Martins; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia; Costa, Daniela CaldeiraAcetaminophen is a common analgesic and antipyretic compound which, when administered in high doses, has been associated with significant morbidity and mortality, secondary to hepatic toxicity. Although this may be due to a direct interaction of reactive acetaminophen metabolites with hepatocyte proteins, recent studies have suggested that reactive species produced by neutrophils also contribute to the pathophysiological process. Researches on the chemical composition of B. trimera show that this plant has bioactive compounds such as flavonoids, related to the organism’s protection against free radicals. Therefore, in the present study, using Fischer rats, the effect of B. trimera on the antioxidant defense system, the production of nitric oxide (NO) and on the expression of nitric oxide synthase (iNOS), superoxide dismutase (SOD), catalase (CAT) and of the subunits of the NADPH oxidase in neutrophils was evaluated in a model of phagocytosis induced by zimosan (ZC3b) and in a model of inflammation induced by acetaminophen. The results show that the treatment with B. trimera improves the defense system of antioxidant and restores the balance ROS / NO that is altered in the inflammatory process induced by APAP. In conclusion, B. trimera extracts exert antioxidant properties by scavenging ROS and decrease the expression of genes responsible by reactive species production in neutrophils.Item Baccharis trimera protects against ethanol induced hepatotoxicity in vitro and in vivo.(2018) Rabelo, Ana Carolina Silveira; Lúcio, Karine de Pádua; Araújo, Carolina Morais; Araújo, Glaucy Rodrigues de; Miranda, Pedro Henrique de Amorim; Carneiro, Ana Cláudia Alvarenga; Ribeiro, Erica Milena de Castro; Silva, Breno de Mello; Lima, Wanderson Geraldo de; Costa, Daniela CaldeiraEthnopharmacological relevance: Baccharis trimera has been traditionally used in Brazil to treat liver diseases. Aim of the study: To evaluate the protective effect of Baccharis trimera in an ethanol induced hepatotoxicity model. Materials and methods: The antioxidant capacity was evaluated in vitro by the ability to scavenged the DPPH radical, by the quantification of ROS, NO and the transcription factor Nrf2. Hepatotoxicity was induced in animals by administration of absolute ethanol for 2 days (acute) or with ethanol diluted for 28 days (chronic). The biochemical parameters of hepatic function (ALT and AST), renal function (urea and creatinine) and lipid profile (total cholesterol, triglycerides and HDL) were evaluated. In addition to antioxidant defense (SOD, catalase, glutathione), oxidative damage markers (TBARS and carbonylated protein), MMP-2 activity and liver histology. Results: Baccharis trimera promoted a decrease in ROS and NO, and at low concentrations promoted increased transcription of Nrf2. In the acute experiment it promoted increase of HDL, in the activity of SOD and GPx, besides diminishing TBARS and microesteatosis. Already in the chronic experiment B. trimera improved the hepatic and renal profile, decreased triglycerides and MMP-2 activity, in addition to diminishing microesteatosis. Conclusion: We believe that B. trimera action is possibly more associated with direct neutralizing effects or inhibition of reactive species production pathways rather than the modulation of the antioxidant enzymes activity. Thus it is possible to infer that the biological effects triggered by adaptive responses are complex and multifactorial depending on the dose, the time and the compounds used.Item Caspofungin effects on electrocardiogram of mice : an evaluation of cardiac safety.(2021) Paula, Danielle Cristiane Correa de; Leite, Elaine Amaral; Araújo, Carolina Morais; Branquinho, Renata Tupinambá; Guimarães, Homero Nogueira; Guimarães, Andrea GrabeCaspofungin is an echinocandin, exhibiting efcacy against most Candida species invasive infection. Its cardiotoxicity was reported in isolated rat heart and ventricular myocytes, but in vivo and clinical studies are insufcient. Our objective was to evaluate caspofungin in vivo cardiac efects using an efcacious dose against Candida albicans. Female Swiss mice were infected with C. albicans, and treated with caspofungin, 5 or 10 mg/kg, intraperitoneal along 5 days. Survival rate and colony forming units (CFU) into vital organs were determined. For cardiac efects study, mice were treated with caspofungin 10 mg/ kg, and electrocardiogram (ECG) signal was obtained on C. albicans-infected mice, single dose-treated, and uninfected mice treated along 5 days, both groups to measure ECG intervals. Besides, ECG was also obtained by telemetry on uninfected mice to evaluate heart rate variability (HRV) parameters. The MIC for caspofungin on the wild-type C. albicans SC5314 strain was 0.3 μg/ml, indicating the susceptible. Survival rate increased signifcantly in infected mice treated with caspo fungin compared to mice treated with vehicle. None of the survived infected mice presented positive CFU after treatment with 10 mg/kg. C. albicans infection induced prolongation of QRS, QT, and QTc intervals; caspofungin did not alter this efect. Caspofungin induced increase of PR and an additional increase of QRS after 24 h of a single dose in infected mice. No signifcant alterations occurred in ECG intervals and HRV parameters of uninfected mice, after caspofungin treatment. Caspofungin showed in vivo cardiac relative safety maintaining its antifungal efcacy against C. albicans.Item Lycopene inhibits reactive oxygen species production in SK-Hep-1 cells and attenuates acetaminophen-induced liver injury in C57BL/6 mice.(2017) Bandeira, Ana Carla Balthar; Silva, Talita Prato da; Araújo, Glaucy Rodrigues de; Araújo, Carolina Morais; Silva, Rafaella Cecília da; Lima, Wanderson Geraldo de; Bezerra, Frank Silva; Costa, Daniela CaldeiraOur aim was to investigate the antioxidant potential of lycopene in different experimental liver models: in vitro, to evaluate the influence of lycopene on reactive oxygen species (ROS) production mediated by the PKC pathway and in vivo, to evaluate the protective effects of lycopene in an experimental model of hepatotoxicity. The in vitro study assessed the lycopene antioxidant potential by the quantification of ROS production in SK-Hep-1 cells unstimulated or stimulated by an activator of the PKC pathway. The role of NADPH oxidase was evaluated by measuring its inhibition potential using an inhibitor of this enzyme. In the in vivo study, male C57BL/6 mice received lycopene (10 or 100 mg/kg by oral gavage) and 1 h later, acetaminophen (APAP) (500 mg/kg) was administrated. Lycopene decreased ROS production in SK-Hep- 1 cells through inhibition of NADPH oxidase, brought about in the PKC pathway. Lycopene improved hepatotoxicity acting as an antioxidant, reduced GSSG and regulated tGSH and CAT levels, reduced oxidative damage primarily by decreasing protein carbonylation, promoted the downregulation of MMP- 2 and reduced areas of necrosis improving the general appearance of the lesion in C57BL/6 mice. Lycopene is a natural compound that was able to inhibit the production of ROS in vitro and mitigate the damage caused by APAP overdose in vivo.Item Oral formulation of DPP-4 inhibitor plus Quercetin improves metabolic homeostasis in type 1 diabetic rats.(2018) Miranda, Pedro Henrique de Amorim; Lacerda, Kíssyla Christine Duarte; Araújo, Carolina Morais; Barichello, José Mario; Lima, Wanderson Geraldo de; Costa, Daniela CaldeiraThis study aimed to investigate the potential of an oral formulation (QV formulation) containing Quercetin and a Dipeptidyl Peptidase-4 Inhibitor (DPP-4 inhibitor), Vildagliptin, in improving metabolic homeostasis in type 1 diabetes model. Female albino Fischer rats were divided into four groups: untreated control animals (C), untreated diabetic animals (D), diabetic animals treated with QV formulation (DQV), and diabetic animals treated with insulin (DI). Diabetes was induced by injection of alloxan (135 mg kg body mass)−1 and confirmed by glycemic test. After the 30-day treatment period, biochemical parameters were analyzed in the pancreas, liver, and serum. Histopathological changes in pancreatic tissue were examined by Hematoxyline & Eosin staining and the insulin content in the islet measured by immunohistochemistry with anti-insulin antibody. The glycogen content in the hepatocytes was quantified by Periodic Schiff Acid staining. The QV formulation reduced the glycemia, preserved the pancreatic architecture, increased insulin levels, furthermore ameliorated lipid profile and to promote higher survival rate of animals. Together, our data suggest that the QV formulation treatment was able to normalize metabolic homeostasis in type 1 diabetic rats.Item Swimming training promotes cardiac remodeling and alters the expression of mRNA and protein levels involved in calcium handling in hypertensive rats.(2014) Locatelli, Jamille; Assis, Leonardo Vinícius Monteiro de; Araújo, Carolina Morais; Alzamora, Andréia Carvalho; Lima, Wanderson Geraldo de; Santos, Maria José Campagnole dos; Santos, Robson Augusto Souza dos; Isoldi, Mauro CésarAim: The aim of this study was to identify the effects of swimming training on the mRNA expression and protein levels of the calcium handling proteins in the hearts of renovascular hypertensive rats submitted to swimming protocol during 6 weeks. Main methods: Fischer ratswith renovascular hypertension 2-kidney 1-clip (2K1C) and SHAMgroups were divided among sedentary and exercised groups. The exercise protocol lasted for 6 weeks (1 h/day, 5×/week), and the mean arterial pressure, cardiomyocytes hypertrophy parameters, mRNA expression and protein levels of some calcium handling proteins in the left ventricle were evaluated. Key findings: Swimming training was able to reduce the levels of mean arterial pressure in the hypertensive group compared to 2K1C SED, and to promote cardiac hypertrophy in SHAM EX and 2K1C EX groups in comparison to the respective control groups. The mRNA levels of B-type natriuretic peptide were reduced in the 2K1C EX when compared to 2K1C SED. The mRNA and protein levels of the sarcoplasmic reticulumCa2+-ATPase increased after the swimming training in SHAMand 2K1C groups. ThemRNA and protein levels of phospholamban, displayed an increase in their levels in the exercised SHAMand in hypertensive rats in comparison to their respective controls; while mRNA levels of Na+/Ca2+ exchanger was reduced in the left ventricle comparing to the sedentary hypertensive rats. Significance: Taken altogether,we provide evidence that the aerobic training may lead to cardiac remodeling, and modulate the calcium handling proteins expression in the heart of hypertensive rats.