RESUMEN
BACKGROUND: Chronic Chagas cardiomyopathy (CCC) is caused by an inflammatory process induced by Trypanosoma cruzi, which leads to myocarditis with reactive and reparative fibrosis. CCC progresses with myocardial perfusion abnormalities and histopathological events that affect cardiorespiratory fitness (CRF). OBJECTIVES: We evaluated the effects of aerobic physical training (APT) on myocardial perfusion and on morphological and functional impairments related with inflammation and fibrosis in Syrian hamsters with CCC. As a secondary objective, we analyzed the cross-sectional areas of the skeletal muscle. METHODS: Hamsters with CCC and their respective controls were divided into four groups: CCC sedentary, CCC-APT, sedentary control and APT control. Seven months after infection, the animals underwent echocardiography, myocardial perfusion scintigraphy and cardiopulmonary exercise testing. Moderate-intensity APT was performed for fifty minutes, five times a week, for eight weeks. Subsequently, the animals were reassessed. Histopathological analysis was conducted after the above-mentioned procedures. The level of significance was set at 5% in all analyses (p<0.05). RESULTS: CCC sedentary animals presented worse myocardial perfusion defects (MPD) over time, reduced left ventricle ejection fraction (LVEF) and showed more inflammation and fibrosis when compared to other groups (mixed ANOVA analysis). Conversely, APT was able to mitigate the progression of MPD, ameliorate inflammation and fibrosis and improve CRF efficiency in CCC-APT animals. CONCLUSIONS: Our study demonstrated that APT ameliorated cardiac dysfunction, MPD, and reduced inflammation and fibrosis in CCC hamster models. Additionally, CCC-SED animals presented skeletal muscle atrophy while CCC-APT animals showed preserved skeletal muscle CSA. Understanding APT's effects on CCC's pathophysiological dimensions is crucial for future research and therapeutic interventions.
FUNDAMENTO: A Cardiomiopatia Chagásica Crônica (CCC) é causada por um processo inflamatório induzido pelo Trypanosoma cruzi, que leva à miocardite com fibrose reativa e reparativa. A CCC progride com alterações de perfusão miocárdica e eventos histopatológicos que afetam a Aptidão Cardiorrespiratória (ACR). OBJETIVOS: Avaliamos os efeitos do Treinamento Físico Aeróbico (TFA) na perfusão miocárdica e nos comprometimentos morfológicos e funcionais relacionados à inflamação e fibrose em hamsters sírios com CCC. Como objetivo secundário, analisamos as áreas de secção transversa do músculo esquelético. MÉTODOS: Hamsters com CCC e seus respectivos controles foram divididos em quatro grupos: CCC sedentário, CCC-TFA, controle sedentário e controle TFA. Sete meses após a infecção, os animais foram submetidos à ecocardiografia, à cintilografia de perfusão miocárdica e ao teste de esforço cardiopulmonar. TFA de intensidade moderada foi realizado durante cinquenta minutos, cinco vezes por semana, por oito semanas. Posteriormente, os animais foram reavaliados. A análise histopatológica foi realizada após os procedimentos acima mencionados. O nível de significância foi estabelecido em 5% em todas as análises (p<0,05). RESULTADOS: Animais com CCC sedentários apresentaram piores Defeitos de Perfusão Miocárdica (DPM) ao longo do tempo, Fração de Ejeção do Ventrículo Esquerdo (FEVE) reduzida, e apresentaram mais inflamação e fibrose quando comparados aos demais grupos (análise ANOVA mista). Por outro lado, o TFA foi capaz de mitigar a progressão do DPM, atenuar a inflamação e a fibrose e melhorar a eficiência da ACR em animais CCC-TFA. CONCLUSÃO: Nosso estudo demonstrou que o TFA melhorou a disfunção cardíaca, DPM e reduziu a inflamação e a fibrose em modelos de hamster com CCC. Além disso, os animais CCC-SED apresentaram atrofia do músculo esquelético, enquanto os animais CCC-TFA apresentaram a AST do músculo esquelético preservada. Compreender os efeitos da TFA nas dimensões fisiopatológicas da CCC é crucial para futuras pesquisas e intervenções terapêuticas.
Asunto(s)
Cardiomiopatía Chagásica , Modelos Animales de Enfermedad , Fibrosis , Condicionamiento Físico Animal , Animales , Cardiomiopatía Chagásica/fisiopatología , Cardiomiopatía Chagásica/terapia , Condicionamiento Físico Animal/fisiología , Enfermedad Crónica , Masculino , Miocardio/patología , Ecocardiografía , Cricetinae , Inflamación , Factores de Tiempo , Mesocricetus , Músculo Esquelético/fisiopatología , Músculo Esquelético/patología , Prueba de Esfuerzo , Imagen de Perfusión Miocárdica/métodos , Reproducibilidad de los Resultados , Miocarditis/fisiopatología , Miocarditis/terapiaRESUMEN
Radiolabeled peptides with high specificity to receptors expressed on tumor cells hold a great promise as diagnostic and therapeutic tracers. The main objective of this study was to evaluate the radiochemical and biological properties of two [131I]I-peptides, as well as their interaction with the epidermal growth factor receptor (EGFR), overexpressed in a wide variety of tumors, including glioblastoma. The EEEEYFELV peptide and its analogue DEDEYFELV, both designed to interact with EGFR, were chemically synthesized, purified and radiolabeled with iodine-131 ([131I]NaI). The radioiodination was evaluated and optimized using the chloramine-T methodology. The stability, serum proteins binding and partition coefficient were assessed for both radioconjugates. Moreover, the binding and internalization of synthesized radiopeptides with rat glioblastoma cells (C6) and with rat brain homogenates from a glioblastoma induced model were evaluated and ex vivo biodistribution studies were performed. Under optimized radiolabeling conditions, the peptides showed an average radiochemical yield of 90-95%. The stability studies showed that both peptides were stable up to 24 h in reaction medium, saline, and human serum. Furthermore, [131I]I-peptides have hydrophilic features and showed binding percentage to serum proteins of around 50%, which is highly compatible with clinical applications. Moreover, the radiopeptides presented capacity for binding and internalization in both tumor cells (C6) and rat brain tissues after tumor induction. Biodistribution studies corroborated the cell culture studies and confirmed the different binding characteristics derived from a simple change of two amino acids (Glu â Asp1,3) in their sequences. The results obtained are consistent enough to motivate further studies. Thereby, these radiolabeled peptides might be useful for diagnostic applications.