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Diethylcarbamazine: A potential treatment drug for pulmonary hypertension?
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.
Afiliación
  • Ribeiro EL; Laboratory of Ultrastructure, Aggeu Magalhães Research Center - CPqAM, Pernambuco, Brazil; Federal University of Pernambuco, Brazil.
  • Fragoso IT; Laboratory of Ultrastructure, Aggeu Magalhães Research Center - CPqAM, Pernambuco, Brazil; Federal University of Pernambuco, Brazil.
  • Gomes FODS; Laboratory of Ultrastructure, Aggeu Magalhães Research Center - CPqAM, Pernambuco, Brazil; Federal University of Pernambuco, Brazil.
  • Oliveira AC; Laboratory of Ultrastructure, Aggeu Magalhães Research Center - CPqAM, Pernambuco, Brazil; Federal University of Pernambuco, Brazil.
  • Silva AKSE; Laboratory of Ultrastructure, Aggeu Magalhães Research Center - CPqAM, Pernambuco, Brazil; Federal University of Pernambuco, Brazil.
  • Silva PME; Laboratory of Inflammation, FIOCRUZ, Rio de Janeiro, Brazil.
  • Ciambarella BT; Laboratory of Inflammation, FIOCRUZ, Rio de Janeiro, Brazil.
  • Ramos IPR; National Center Structural Biology and Bio-imaging, Carlos Chagas Filho Biophysics Institute, Department of Radiology, University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • Peixoto CA; Laboratory of Ultrastructure, Aggeu Magalhães Research Center - CPqAM, Pernambuco, Brazil. Electronic address: cpeixoto@cpqam.fiocruz.br.
Toxicol Appl Pharmacol ; 333: 92-99, 2017 10 15.
Article en En | MEDLINE | ID: mdl-28851623
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dietilcarbamazina / Hipertensión Pulmonar Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Toxicol Appl Pharmacol Año: 2017 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dietilcarbamazina / Hipertensión Pulmonar Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Toxicol Appl Pharmacol Año: 2017 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos