Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/28978
Title: Pharmacological inhibition of transforming growth factor beta signaling decreases infection and prevents heart damage in acute Chagas' disease
Authors: Waghabi, Mariana C.
Souza, Elen M. de
Oliveira, Gabriel M. de
Keramidas, Michelle
Feige, Jean-Jacques
Araujo-Jorge, Tania C.
Bailly, Sabine
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil / Institut National de la Santé et de la Recherche Médicale. Grenoble, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.
Commissariat a` l’Energie Atomique. Institut de Recherches en Technologies et Sciences pour le Vivant/ Laboratoire Angiogenèse et Physiopathologie Vasculaire. 5 and Université Joseph Fourier,6. Grenoble, France.
Commissariat a` l’Energie Atomique. Institut de Recherches en Technologies et Sciences pour le Vivant/ Laboratoire Angiogenèse et Physiopathologie Vasculaire. 5 and Université Joseph Fourier,6. Grenoble, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
Commissariat a` l’Energie Atomique. Institut de Recherches en Technologies et Sciences pour le Vivant/ Laboratoire Angiogenèse et Physiopathologie Vasculaire. 5 and Université Joseph Fourier,6. Grenoble, France.
Abstract: Chagas' disease induced by Trypanosoma cruzi infection is an important cause of mortality and morbidity affecting the cardiovascular system for which presently available therapies are largely inadequate. We previously reported that transforming growth factor beta (TGF-beta) is implicated in several regulatory aspects of T. cruzi invasion and growth and in host tissue fibrosis. This prompted us to evaluate the therapeutic action of an inhibitor of TGF-beta signaling (SB-431542) administered during the acute phase of experimental Chagas' disease. Male Swiss mice were infected intraperitoneally with 10(4) trypomastigotes of T. cruzi (Y strain) and evaluated clinically for the following 30 days. SB-431542 treatment significantly reduced mortality and decreased parasitemia. Electrocardiography showed that SB-431542 treatment was effective in protecting the cardiac conduction system. By 14 day postinfection, enzymatic biomarkers of tissue damage indicated that muscle injury was decreased by SB-431542 treatment, with significantly lower blood levels of aspartate aminotransferase and creatine kinase. In conclusion, inhibition of TGF-beta signaling in vivo appears to potently decrease T. cruzi infection and to prevent heart damage in a preclinical mouse model. This suggests that this class of molecules may represent a new therapeutic agent for acute and chronic Chagas' disease that warrants further clinical exploration.
Keywords: Chagas Disease
Transforming Growth Factor B
Pharmacological Inhibition
heart
Infection
keywords: Doença de Chagas
Indicação farmacológica
Prevenção
Infecção
Coração
Fator de Crescimento Transformador B
Issue Date: 2009
Publisher: American Society for Microbiology
Citation: WAGHABI, Mariana C. et al. Pharmacological Inhibition of Transforming Growth Factor Signaling Decreases Infection and Prevents Heart Damage in Acute Chagas’ Disease. Antimicrobial Agents and Chemotherapy, v.53, n.11, p.4694-4701, nov. 2009.
DOI: 10.1128/AAC.00580-09
ISSN: 0066-4804
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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