Navegando por Autor "Penitente, Arlete Rita"
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Item Basal and β-Adrenergic cardiomyocytes contractility dysfunction induced by dietary protein restriction is associated with downregulation of SERCA2a expression and disturbance of endoplasmic reticulum Ca2+ regulation in rats.(2014) Penitente, Arlete Rita; Novaes, Rômulo Dias; Silva, Marcelo Eustáquio; Silva, Márcia Ferreira da; Quintão Júnior, Judson Fonseca; Guatimosim, Silvia; Cruz, Jader dos Santos; Chianca Júnior, Deoclécio Alves; Natali, Antônio José; Neves, Clóvis AndradeBackground: The mechanisms responsible for the cardiac dysfunction associated with dietary protein restriction (PR) are poorly understood. Thus, this study was designed to evaluate the effects of PR on calcium kinetics, basal and β-adrenergic contractility in murine ventricular cardiomyocytes. Methods: After breastfeeding male Fisher rats were distributed into a control group (CG, n = 20) and a protein-restricted group (PRG, n = 20), receiving isocaloric diets for 35 days containing 15% and 6% protein, respectively. Biometric and hemodynamic variables were measured. After euthanasia left ventricles (LV) were collected for histopathological evaluation, SERCA2a expression, cardiomyocytes contractility and Ca2+ sparks analysis. Results: PRG animals showed reduced general growth, increased heart rate and arterial pressure. These animals presented extracellular matrix expansion and disorganization, cardiomyocytes hypotrophy, reduced amplitudes of shortening and maximum velocity of contraction and relaxation at baseline and after β-adrenergic stimulation. Reduced SERCA2a expression as well as higher frequency and lower amplitude of Ca2+ sparks were observed in PRG cardiomyocytes. Conclusion: The observations reveal that protein restriction induces marked myocardial morphofunctional damage. The pathological changes of cardiomyocyte mechanics suggest the potential involvement of the β-adrenergic system, which is possibly associated with changes in SERCA2a expression and disturbances in Ca2+ intracellular kinetics.Item Effects of Trypanosoma cruzi infection on myocardial morphology, single cardiomyocyte contractile function and exercise tolerance in rats.(2011) Novaes, Rômulo Dias; Penitente, Arlete Rita; Gonçalves, Reggiani Vilela; Silva, André Talvani Pedrosa da; Neves, Clóvis Andrade; Maldonado, Izabel Regina dos Santos Costa; Natali, Antônio JoséThe aim of this study was to investigate the effects of Trypanosoma cruzi (T. cruzi) infection on myocardial morphology, single cardiomyocyte contractile function and exercise tolerance in rats. Adult Wistar rats were randomized into control (n = 14) and infected (n = 14) groups. Infected animals were inoculated with T. cruzi Y strain (300,000 trypomastigotes ⁄ 50 g body weight). After 9 weeks, the animals were subjected to a treadmill running protocol. Then, the right atrium (RA) and left ventricle (LV) were removed for morphological and cell contractile evaluation. The infected animals exhibited a significant reduction in distance travelled, total time to fatigue and workload. In addition, these animals had hypertrophy, increased myocardial cellularity, and an increase in the proportion of collagen and blood vessels. RA and LV myocytes from infected animals showed marked contractile dysfunction under basal conditions and a reduced contractile response to b-adrenergic stimulation. The workload of infected animals was correlated closely with the amplitude of cell shortening of RA and LV myocytes. T. cruzi infection influenced the myocardial morphology and the mechanical properties of RA and LV single myocytes negatively and reduced exercise tolerance. Single cardiomyocyte contractile dysfunction could constitute an additional mechanism of cardiac impairment and reduced exercise tolerance in this infection.Item Enalapril in combination with benznidazole reduces cardiac inflammation and creatine kinases in mice chronically infected with Trypanosoma cruzi.(2015) Penitente, Arlete Rita; Leite, Ana Luísa Junqueira; Costa, Guilherme de Paula; Bajracharya, Deena Shrestha; Horta, Aline Luciano; Natali, Antônio José; Neves, Clóvis AndradeThe protozoan Trypanosoma cruzi triggers an inflammatory process in mammalian heart causing events such as fibrosis, changes in the architecture and functionality in this organ. Enalapril, an angiotensin II-converting enzyme inhibitor, is a drug prescribed to ameliorate this heart dysfunction, and appears to exert a potential role in immune system regulation. Our aim was to evaluate the chronic cardiac inflammatory parameters after therapeutic treatment with enalapril and benznidazole in C57BL/6 mice infected with the VL-10 strain of T. cruzi. After infection, animals were treated with oral doses of enalapril (25 mg/kg), benznidazole (100 mg/kg), or both during 30 days. Morphometric parameters and levels of chemokines (CCL2, CCL5), IL-10, creatine kinases (CKs), and C-reactive protein were evaluated in the heart and serum at the 120th day of infection. Enalapril alone or in combination with benznidazole did not change the number of circulating parasites, but reduced cardiac leukocyte recruitment and total collagen in the cardiac tissue. Interestingly, the combination therapy (enalapril/benznidazole) also reduced the levels of chemokines, CK and CK-MB, and C-reactive proteins in chronic phase. In conclusion, during the chronic experimental T. cruzi infection, the combination therapy using enalapril plus benznidazole potentiated their immunomodulatory effects, resulting in a low production of biomarkers of cardiac lesionsItem High fat diet modulates inflammatory parameters in the heart and liver during acute Trypanosoma cruzi infection.(2018) Figueiredo, Vivian Paulino; Lopes Júnior, Evandro Saraiva; Lopes, Laís Roquete; Simões, Natalia Figuerôa; Penitente, Arlete Rita; Bearzoti, Eduardo; Vieira, Paula Melo de Abreu; Schulz, Richard; Silva, André Talvani Pedrosa daThe high fat diet (HFD) can trigger metabolic and cardiovascular diseases. Trypanosoma cruzi infection induces progressive inflammatory manifestations capable to affect the structure and the function of important organs such as the heart and liver. Here we aimed to investigate the effects of a HFD on the immune response and matrix metalloproteinase (MMP) activities during acute infection with the T. cruzi strain VL-10. The VL-10 strain has cardiac tropism and causes myocarditis in mice. Male C57BL/6 mice were treated with either: (i) regular diet (Reg) or (ii) HFD for 8 weeks, after which mice in each group were infected with T. cruzi. Mice were euthanized on day 30 after infection, and the liver and heart were subjected to histology and zymography to determine MMP-2 activities and plasma levels of IL-10, TNF, CCL2, and CCL5. T. cruzi-infected HFD animals had higher parasitemia, LDL and total cholesterol levels. Regardless of diet, plasma levels of all inflammatory mediators and cardiac MMP-2 activity were elevated in infected mice in contrast with the low plasma levels of leptin. HFD animals presented micro- and macrovesicular hepatic steatosis, while cardiac leukocyte infiltration was mainly detected in T. cruzi-infected mice. Our findings suggested that a HFD promotes higher circulating T. cruzi load and cardiac and liver immunopathogenesis in an experimental model using the VL-10 strain of the T. cruzi.Item Malnutrition enhances cardiovascular responses to chemoreflex activation in awake rats.(2007) Penitente, Arlete Rita; Fernandes, Luciano Gonçalves; Cardoso, Leonardo Máximo; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia; Silva, Antônio Leite; Haibara, Andréa Siqueira; Moraes, Márcio Flávio Dutra; Chianca Júnior, Deoclécio AlvesSeveral studies in the literature suggest that low-protein intake is associated with increases in sympathetic efferent activity and cardiovascular disease. Among the possible mechanisms, changes in the neurotransmission of cardiovascular reflexes have been implicated. Therefore, the present study comprised the evaluation of chemoreflex responsiveness in rats subjected to a low-protein diet during the 35 days after weaning. As a result, we observed that malnourished rats presented higher levels of baseline mean arterial pressure and heart rate and exhibited a mild increase in the pressor response to chemoreflex activation. They also exhibited a massive bradycardic response to chemoreflex activation. Interestingly, bilateral ligature of the carotid body arteries further increased baseline mean arterial pressure and heart rate in malnourished animals. The data suggest severe autonomic imbalance and/or change in the central interplay between neural and cardiovascular mechanisms.Item Modulation of inflammatory and oxidative status by exercise attenuates cardiac morphofunctional remodeling in experimental Chagas cardiomyopathy.(2016) Novaes, Rômulo Dias; Gonçalves, Reggiani Vilela; Penitente, Arlete Rita; Bozi, Luiz Henrique Marchesi; Neves, Clóvis Andrade; Maldonado, Izabel Regina dos Santos Costa; Natali, Antônio José; Silva, André Talvani Pedrosa daAims: The rational basis that explains the benefits of exercise therapy on Chagas cardiomyopathy (ChC) is poorly understood. This study investigated the impact of an exercise programon exercise performance, heart parasitism, immunoinflammatory response, fibrogenesis, oxidative damage, and cardiomyocytes contractility in experimental ChC. Main methods: Wistar rats were subjected to a 9-week treadmill running training and challenged with Trypanosoma cruzi. Control animals remained sedentary. Physical and metabolic performance, cardiac morphology, cytokines, chemokines, nitric oxide, oxidative tissue damage, cardiomyocyte morphology and contractility were analyzed. Key findings: Exercise training was efficient to improve physical performance and anaerobic threshold in trained animals. By increasing cardiac and serum levels of cytokines (TNF-α, IFN-γ, and IL-6), chemokines (MCP-1 and CX3CL1), the myocardial activity catalase and superoxide dismutase, and reducing lipid and protein oxidation in cardiac tissue, exercise training seem to be a beneficial strategy to mitigate the progression and severity of Chagas-associated cardiomyopathy. Significance: The protective adaptations to the host triggered by exercise training contributed to reduce cardiac parasitism, inflammation, fibrosis and cardiomyocytes atrophy. Although exercise training does not affect nitric oxide levels in cardiac tissue from infected animals, this strategy enhanced the efficiency of endogenous antioxidant mechanisms, restricting oxidative tissue damage with positive repercussions to cardiomyocytes biomechanics in rats.Item Parasite control and skeletal myositis in Trypanosoma cruzi-infected and exercised rats.(2017) Novaes, Rômulo Dias; Gonçalves, Reggiani Vilela; Penitente, Arlete Rita; Cupertino, Marli do Carmo; Maldonado, Izabel Regina dos Santos Costa; Silva, André Talvani Pedrosa da; Natali, Antônio JoséNon-pharmacological strategies have been rarely described in the treatment of infectious diseases.Although exercise training has been recently incorporated in the clinical management of Chagas disease,the rationale basis that supports this indication is poorly understood. Thus, we investigated the effectof an aerobic exercise on the parasitism, inflammation and oxidative tissue damage in a murine modelof Trypanosoma cruzi-induced skeletal myositis. Wistar rats were randomized into four groups: trainednot infected (TNI) and infected (TI), sedentary not infected (SNI) and infected (SI). A running trainingprogram was administered 5 days/week for 9 weeks. Then, infected animals were inoculated with T. cruziand followed up for another 9 weeks. Exercise training induced beneficial adaptations by increasing timeto fatigue and lactate threshold in TNI and TI animals. SI animals presented higher parasitemia, skele-tal muscle parasitism, cell necrosis, leukocyte infiltration, cytokines levels, reactive oxygen species andnitric oxide production, thiobarbituric acid reactive substances, carbonyl proteins, myosin heavy chain Idepletion, and increased catalase (CAT) and superoxide dismutase (SOD) activities. Beyond attenuationin all these variables, TI animals showed reduced TNF- , CCL-2/MCP-1 and CX3CL1, and increased IL-10muscle levels. Furthermore, these animals presented higher CAT and SOD activities and reduced lipidand protein oxidation. Taken together, our findings indicated that exercise training induced a protectivephenotype in T. cruzi-infected mice, enhancing host defenses against the parasite and attenuating thepathological remodeling associated with skeletal myositis, aspects potentially associated to an improvedimmunological and redox balance in infected animals.Item Participação dos quimiorreceptores carotídeos sobre a regulação cardiovascular em ratos desnutridos.(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., 2006) Penitente, Arlete Rita; Chianca Júnior, Deoclécio AlvesAs complicações decorrentes de doenças cardiovasculares, como a hipertensão arterial, têm levado à morte grande número de pessoas todos os anos. Vários modelos experimentais têm sido desenvolvidos no sentido de elucidar os mecanismos que levam ao aumento crônico da pressão arterial e a desnutrição parece ser um dos fatores para esta patologia. Nosso Laboratório vem estudando mecanismos de controle da função cardiovascular em modelos de desnutrição. Resultados anteriores mostraram alterações em alguns mecanismos reflexos; barorreflexo e reflexo Bezold-Jarish, além de uma maior atividade simpática vasomotora. Dessa maneira, o objetivo principal deste estudo foi avaliar a participação dos quimiorreceptores carotídeos sobre a regulação cardiovascular, em ratos submetidos à desnutrição protéica. Foram utilizados ratos machos, Fisher, divididos em quatro grupos de acordo com o seguinte teor de proteína: controle, 15% de proteína durante 35 dias (n=18); controle desnervado (n=08), desnutrido, 6% de proteína (n=18) e desnutrido desnervado (n=08). Vinte e quatro horas antes do experimento, fora implantados cateteres na artéria e veia femorais para registro de PAM e FC e administração das drogas, respectivamente. O quimiorreflexo foi avaliado utilizando injeções endovenosas de cianeto de potássio (KCN) nas doses 5, 10, 15, 20 e 40 µg/0,1 mL/rato. Os ratos foram submetidos a desnervação seletiva dos quimiorreceptores carotídeos e 24 horas após, realizaram-se novos registros de PAM e FC. Os resultados mostraram que os ratos desnutridos apresentaram níveis elevados de PAM e FC em relação aos controles (139±3 mmHg e 442±13 bpm) e (115±2 mmHg e 401±8 bpm), respectivamente. Nos ratos desnutridos as respostas pressoras induzidas pelo KCN, mostraram-se potencializadas quando comparadas aos controles. Da mesma forma, as respostas bradicárdicas ao KCN foram potencializadas, em média 3 vezes maior, quando comparadas aos controles. Após a desnervação quimiorreflexa os valores basais de PAM e FC, no grupo desnutrido, apresentaram-se elevados quando comparados aos valores antes da desnervação (135±2 mmHg e 448±16 bpm vs. desnutrido pós-desnervação 156±4 mmHg e 531±19 bpm). Corroborando dados da literatura, os ratos do grupo controle não apresentaram diferença significativa nos níveis basais de PAM e FC, antes e após a cirurgia de desnervação quimiorreflexa. Nossos resultados indicam um aumento na responsividade do quimiorreflexo, além disso, a desnervação quimiorreceptora carotídea promoveu um aumento da PAM e FC basais, sugerindo uma participação tônica inibitória na regulação cardiovascular neste modelo de desnutrição.Item Protein restriction after weaning modifies the calcium kinetics and induces cardiomyocyte contractile dysfunction in rats.(2013) Penitente, Arlete Rita; Novaes, Rômulo Dias; Chianca Júnior, Deoclécio Alves; Silva, Márcia Ferreira da; Silva, Marcelo Eustáquio; Souza, Aline Maria Arlindo de; Fonseca, Silvia Carolina Guatimosim; Almeida, Pedro William Machado de; Alves, Márcia Netto Magalhães; Felix, Leonardo Bonato; Neves, Clóvis Andrade; Natali, Antônio JoséProtein restriction (PR) is associated with cardiovascular diseases. The purpose of this study was to investigate the effects on single ventricular cardiomyocyte contractile function of a short-term PR after weaning. Male Fischer rats that were 28 days old were randomly divided into a control group (CG, n = 16) and a protein-restricted group (PRG, n = 16). After weaning, CG and PRG animals received isocaloric diets containing 15 and 6% protein, respectively, for 35 days. Biometric parameters were then measured, and the hearts were removed for the analysis of contractile function and calcium transient in isolated cardiomyocytes of the left ventricule (LV), and the quantification of calcium and collagen fibers in LV myocardium. PRG animals had lower body weight (BW) and LV weight (LVW), an increased LVW to BW ratio and a higher proportion of collagen fibers than CG animals. PRG animals exhibited reduced tissue levels of calcium, reduced the length, width and volume of cardiomyocytes and their sarcomere length compared to CG animals. Cardiomyocytes from PRG animals had a lower amplitude of shortening, a slower time to the peak of shortening and a longer time to half-relaxation than those from the CG. Cardiomyocytes from PRG animals also presented a lower peak of calcium transient and a longer calcium transient decay time than CG animals. Taken together, the results indicate that short-term PR after weaning induces a marked structural remodeling of the myocardium parenchyma and stroma that coexists with contractile dysfunctions in single LV cardiomyocytes of rats, which is probably associated with pathological changes of the intracellular calcium kinetics, rather than inadequate available amounts of this mineral in cardiac tissue.Item The effects of resistance exercise on cognitive function, amyloidogenesis, and neuroinflammation in Alzheimer’s disease.(2023) Azevedo, Caroline Vieira; Hashiguchi, Debora; Campos, Henrique Correia; Santos, Emilly Vitória Figueiredo; Otaviano, Sthefanie Ferreira de Souza Dias; Penitente, Arlete Rita; Arida, Ricardo Mario; Longo, Beatriz MonteiroWith the increasing prevalence of Alzheimer’s disease (AD) and difficulties in finding effective treatments, it is essential to discover alternative therapies through new approaches. In this regard, non-pharmacological therapies, such as physical exercise, have been proposed and explored for the treatment of AD. Recent studies have suggested that resistance exercise (RE) is an effective strategy for promoting benefits in memory and cognitive function, producing neuroprotective and anti-inflammatory effects, and reducing amyloid load and plaques, thereby reducing the risk, and alleviating the neurodegeneration process of AD and other types of dementia in the elderly. In addition, RE is the exercise recommended by the World Health Organization for the elderly due to its benefits in improving muscle strength and balance, and increasing autonomy and functional capacity, favoring improvements in the quality of life of the elderly population, who is more likely to develop AD and other types of dementia. In this mini-review, we discuss the impact of RE on humans affected by MCI and AD, and animal models of AD, and summarize the main findings regarding the effects of RE program on memory and cognitive functions, neurotrophic factors, Aβ deposition and plaque formation, as well as on neuroinflammation. Overall, the present review provides clinical and preclinical evidence that RE plays a role in alleviating AD symptoms and may help to understand the therapeutic potential of RE, thereby continuing the advances in AD therapies.Item Trypanosoma cruzi infection alters glucose metabolism at rest and during exercise without modifying the morphology of pancreatic islets in rats.(2012) Novaes, Rômulo Dias; Gonçalves, Reggiani Vilela; Penitente, Arlete Rita; Silva, André Talvani Pedrosa da; Neves, Clóvis Andrade; Natali, Antônio José; Maldonado, Izabel Regina dos Santos CostaThis study investigated the effects of Trypanosoma cruzi infection on pancreatic morphology and glucose metabolism at rest and during exercise. Wistar rats were randomized into control (CG = 10) and infected (IG = 10) groups. The IG animals were inoculated with T. cruzi Y strain (300,000 trypomastigotes/50 g). After 9 weeks, the animals were subjected to glucose (OGTT) and insulin (ITT) tolerance tests and a treadmill running protocol. Blood glucose, lactate and time to fatigue were determined. After euthanasia, the pancreases were removed for morphological and biochemical analyses. The IG presented abnormal glucose kinetics in OGTT and a similar glucose curve in ITT compared to the CG. During the exercise test, the IG showed anticipation of time to fatigue. At the point of fatigue, no difference was found in blood glucose and lactate between the groups. There was a significant correlation between lactate levels and the time to fatigue. The IG presented marked pancreatic inflammation, fibrosis and protein oxidation. The number of _ cells in the IG animals was not reduced. T. cruzi infection impaired pancreas morphology and glucose metabolism at rest and during exercise in rats, which could constitute an additional mechanism in the induction of exercise intolerance in Chagas’ disease.Item Trypanosoma cruzi infection induces morphological reorganization of the myocardium parenchyma and stroma, and modifies the mechanical properties of atrial and ventricular cardiomyocytes in rats.(2013) Novaes, Rômulo Dias; Penitente, Arlete Rita; Gonçalves, Reggiani Vilela; Silva, André Talvani Pedrosa da; Peluzio, Maria do Carmo Gouveia; Neves, Clóvis Andrade; Natali, Antônio José; Maldonado, Izabel Regina dos Santos CostaBackground: This study investigates morphofunctional adaptations of the heart stroma and parenchyma in rats that are chronically infected with Trypanosoma cruzi. Methods: Four-month-old male Wistar rats were randomized into control (n=14) and infected (n=14) groups. Infected animals were inoculated with T. cruzi Y strain. After 9 weeks, the animals were euthanized, and the right atrium (RA) and left ventricle (LV) were removed for biochemical, stereological, and cardiomyocyte mechanical analyses. Results: Infected animals presented cardiomyocyte atrophy and myocardial fibrosis. For these animals, the total volume, length, surface area, and cross-sectional area of cardiomyocytes were significantly reduced, and the total interstitial and collagen volumes were significantly increased in the RA and LV compared to the controls. The total volume and length of blood vessels were significantly increased in the LV, and the total blood vessel surface area was significantly higher in the RA of infected animals. RA and LV cardiomyocytes from infected animals exhibited a significant reduction in cell shortening (43.02% and 24.98%, respectively), prolongation of the time to the peak of contraction (17.09%) and the time to half relaxation (23.68%) compared to non-infected animals. Lipid hydroperoxides, but not mineral concentrations, were significantly increased in the RA and LV from infected animals, showing an inverse correlation with cell shortening. Conclusions: T. cruzi infection induces global structural remodeling of the RA and LV in rats. This remodeling coexists with cardiomyocyte contractility dysfunction, which is possibly related to the abnormal organization of the myocardial stroma and increased cellular lipid peroxidation.Item Uso de fluorescência em um método de disector modificado para estimar o número de miócitos no tecido cardíaco.(2012) Novaes, Rômulo Dias; Penitente, Arlete Rita; Silva, André Talvani Pedrosa da; Natali, Antônio José; Neves, Clóvis Andrade; Maldonado, Izabel Regina dos Santos CostaFundamento: Métodos convencionais de disector atualmente requerem consideráveis custos financeiros, técnicos e operacionais para estimar o número de células, incluindo cardiomiócitos, em uma área de 3D. Objetivo: Usar a microscopia de fluorescência em um método de disector modificado para determinar o número de miócitos no tecido cardíaco em condições normais e patológicas. Métodos: O estudo empregou ratos Wistar machos com quatro meses de idade e peso de 366,25 ± 88,21 g randomizados em grupos controles (GC, n = 8) e infectados (GI, n = 8). Os animais do GI foram inoculados com cepa Y de T. cruzi (300.000 tripomastigotas/50 g). Após oito semanas, os animais foram pesados e sacrificados. Os Ventrículos Esquerdos (VE) foram removidos para análise estereológica da densidade numérica de cardiomiócitos (Nv [c]) e o número total dessas células no VE (N [c]). Esses parâmetros foram estimados usando um disector fluorescente (DF) e comparados com os métodos convencionais de disector óptico (DO) e disector físico (DFi). Resultados: Em ambos os métodos de disector, os animais do GI apresentaram queda significativa de Nv[c] e N[c] em comparação com os animais do GC (p > 0,05). Uma correlação forte, igual ou superior a 96%, foi obtida entre DF, DO e DFi. Conclusão: O método DF parece ser igualmente confiável para determinar Nv[c] e N[c] em condições normais e patológicas, apresentando algumas vantagens em relação aos métodos convencionais de disector: redução de cortes histológicos e imagens na análise estereológica, redução do tempo de análise das imagens, a construção de DF em microscópios simples, utilizando o modo de epifluorescência, distinção de planos de disector em ampliações inferiores.