Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/23588
Title: Diethylcarbamazine: A potential treatment drug for pulmonary hypertension?
Authors: Ribeiro, Edlene Lima
Fragoso, Ingrid Tavares
Gomes, Fabiana Oliveira dos Santos
Oliveira, Amanda Costa
Silva, Amanda Karoline Soares e
Silva, Patrícia Martins E.
Ciambarella, Bianca Torres
Ramos, Isalira Peroba Rezende
Peixoto, Christina Alves
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, Brasil / Universidade Federal de Pernambuco. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, Brasil / Universidade Federal de Pernambuco. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, Brasil / Universidade Federal de Pernambuco. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, Brasil / Universidade Federal de Pernambuco. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, Brasil / Universidade Federal de Pernambuco. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ. Brasil.
Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Departamento de Radiologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Centro Nacional de Biologia Estrutural e Bio-Imagem. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, Brasil.
Abstract: The present study demonstrated the potential effects of diethylcarbamazine (DEC) on monocrotaline (MCT)-induced pulmonary hypertension. MCT solution (600mg/kg) was administered once per week, and 50mg/kg body weight of DEC for 28days. Three C57Bl/6 male mice groups (n=10) were studied: Control; MCT28, and MCT28/DEC. Echocardiography analysis was performed and lung tissues were collected for light microscopy (hematoxylin-eosin and Masson's trichrome staining), immunohistochemistry (αSMA, FADD, caspase 8, caspase 3, BAX, BCL2, cytochrome C and caspase 9) western blot (FADD, caspase 8, caspase 3, BAX, BCL2, cytochrome C and caspase 9) and qRt-PCR (COL-1α and αSMA). Echocardiography analysis demonstrated an increase in the pulmonary arterial blood flow gradient and velocity in the systole and RV area in the MCT28 group, while treatment with DEC resulted in a significant reduction in these parameters. Deposition of collagen fibers and αSMA staining around the pulmonary arteries was evident in the MCT28 group, while treatment with DEC reduced both. Western blot analysis revealed a decrease in BMPR2 in the MCT28 group, in contrast DEC treatment resulted in a significant increase in the level of BMPR2. DEC also significantly reduced the level of VEGF compared to the MCT28 group. Apoptosis extrinsic and intrinsic pathway markers were reduced in the MCT28 group. After treatment with DEC these levels returned to baseline. The results of this study indicate that DEC attenuates PH in an experimental monocrotaline-induced model by inhibiting a series of markers involved in cell proliferation/death.
Keywords: Diethylcarbamazine
Monocrotaline
Hypertension
Pulmonary apoptosis
keywords: Dietilcarbamazina
Monocrotalina
Hipertensão
Apoptose pulmonar
Issue Date: 2017
Publisher: Elsevier
Citation: RIBEIRO, Edlene Lima; et al. Diethylcarbamazine: A potential treatment drug for pulmonary hypertension?. Toxicology and Applied Pharmacology, v.333, p. 92–99, Aug. 2017.
DOI: 10.1016/j.taap.2017.08.015
ISSN: 0041-008X
Embargo date: 2030-01-01
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos
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