Evaluation of antifibrotic and antifungal combined therapies in experimental pulmonary paracoccidioidomycosis
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1093/mmy/myz100 http://hdl.handle.net/11449/199069 |
Resumo: | Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the Paracoccidioides genus. Most of the patients with chronic form present sequelae, like pulmonary fibrosis, with no effective treatment, leading to impaired lung functions. In the present study, we aimed to investigate the antifibrotic activity of three compounds: pentoxifylline (PTX), azithromycin (AZT), and thalidomide (Thal) in a murine model of pulmonary PCM treated with itraconazole (ITC) or cotrimoxazole (CMX). BALB/c mice were inoculated with P. brasiliensis (Pb) by the intratracheal route and after 8 weeks, they were submitted to one of the following six treatments: PTX/ITC, PTX/CMX, AZT/ITC, AZT/CMX, Thal/ITC, and Thal/CMX. After 8 weeks of treatment, the lungs were collected for determination of fungal burden, production of OH-proline, deposition of reticulin fibers, and pulmonary concentrations of cytokines and growth factors. Pb-infected mice treated with PTX/ITC presented a reduction in the pulmonary concentrations of OH-proline, associated with lower concentrations of interleukin (IL)-6, IL-17, and transforming growth factor (TGF)-β1 and higher concentrations of IL-10 compared to the controls. The Pb-infected mice treated with AZT/CMX exhibited decreased pulmonary concentrations of OH-proline associated with lower levels of TGF-β1, and higher levels of IL-10 compared controls. The mice treated with ITC/Thal and CMX/Thal showed intense weight loss, increased deposition of reticulin fibers, high pulmonary concentrations of CCL3, IFN-γ and VEGF, and decreased concentrations of IL-6, IL-1β, IL-17, and TGF-β1. In conclusion, our findings reinforce the antifibrotic role of PTX only when associated with ITC, and AZT only when associated with CMX, but Thal did not show any action upon addition. |
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Evaluation of antifibrotic and antifungal combined therapies in experimental pulmonary paracoccidioidomycosisParacoccidioides brasiliensisazithromycincotrimoxazoleitraconazolepentoxifyllinepulmonary fibrosisthalidomideParacoccidioidomycosis (PCM) is a systemic mycosis caused by the Paracoccidioides genus. Most of the patients with chronic form present sequelae, like pulmonary fibrosis, with no effective treatment, leading to impaired lung functions. In the present study, we aimed to investigate the antifibrotic activity of three compounds: pentoxifylline (PTX), azithromycin (AZT), and thalidomide (Thal) in a murine model of pulmonary PCM treated with itraconazole (ITC) or cotrimoxazole (CMX). BALB/c mice were inoculated with P. brasiliensis (Pb) by the intratracheal route and after 8 weeks, they were submitted to one of the following six treatments: PTX/ITC, PTX/CMX, AZT/ITC, AZT/CMX, Thal/ITC, and Thal/CMX. After 8 weeks of treatment, the lungs were collected for determination of fungal burden, production of OH-proline, deposition of reticulin fibers, and pulmonary concentrations of cytokines and growth factors. Pb-infected mice treated with PTX/ITC presented a reduction in the pulmonary concentrations of OH-proline, associated with lower concentrations of interleukin (IL)-6, IL-17, and transforming growth factor (TGF)-β1 and higher concentrations of IL-10 compared to the controls. The Pb-infected mice treated with AZT/CMX exhibited decreased pulmonary concentrations of OH-proline associated with lower levels of TGF-β1, and higher levels of IL-10 compared controls. The mice treated with ITC/Thal and CMX/Thal showed intense weight loss, increased deposition of reticulin fibers, high pulmonary concentrations of CCL3, IFN-γ and VEGF, and decreased concentrations of IL-6, IL-1β, IL-17, and TGF-β1. In conclusion, our findings reinforce the antifibrotic role of PTX only when associated with ITC, and AZT only when associated with CMX, but Thal did not show any action upon addition.Faculdade de Ciências. Universidade Estadual Paulista (UNESP)MS, Faculdade de Medicina (FAMED). Universidade Federal do Mato Grosso do Sul (UFMS). 79070-900 Campo GrandeInstituto Lauro de Souza Lima (ILSL)Faculdade de Medicina de Botucatu. Universidade Estadual Paulista (UNESP)Faculdade de Ciências. Universidade Estadual Paulista (UNESP)Faculdade de Medicina de Botucatu. Universidade Estadual Paulista (UNESP)Universidade Estadual Paulista (Unesp)Universidade Federal de Mato Grosso do Sul (UFMS)Instituto Lauro de Souza Lima (ILSL)Finato, Angela C. [UNESP]Almeida, Débora F [UNESP]Dos Santos, Amanda R. [UNESP]Nascimento, Dejair C.Cavalcante, Ricardo S. [UNESP]Mendes, Rinaldo P. [UNESP]Soares, Cléverson TPaniago, Anamaria M MVenturini, James2020-12-12T01:29:58Z2020-12-12T01:29:58Z2020-07-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article667-678http://dx.doi.org/10.1093/mmy/myz100Medical mycology, v. 58, n. 5, p. 667-678, 2020.1460-2709http://hdl.handle.net/11449/19906910.1093/mmy/myz1002-s2.0-85087465833Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengMedical mycologyinfo:eu-repo/semantics/openAccess2021-10-23T02:54:13Zoai:repositorio.unesp.br:11449/199069Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T02:54:13Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Evaluation of antifibrotic and antifungal combined therapies in experimental pulmonary paracoccidioidomycosis |
title |
Evaluation of antifibrotic and antifungal combined therapies in experimental pulmonary paracoccidioidomycosis |
spellingShingle |
Evaluation of antifibrotic and antifungal combined therapies in experimental pulmonary paracoccidioidomycosis Finato, Angela C. [UNESP] Paracoccidioides brasiliensis azithromycin cotrimoxazole itraconazole pentoxifylline pulmonary fibrosis thalidomide |
title_short |
Evaluation of antifibrotic and antifungal combined therapies in experimental pulmonary paracoccidioidomycosis |
title_full |
Evaluation of antifibrotic and antifungal combined therapies in experimental pulmonary paracoccidioidomycosis |
title_fullStr |
Evaluation of antifibrotic and antifungal combined therapies in experimental pulmonary paracoccidioidomycosis |
title_full_unstemmed |
Evaluation of antifibrotic and antifungal combined therapies in experimental pulmonary paracoccidioidomycosis |
title_sort |
Evaluation of antifibrotic and antifungal combined therapies in experimental pulmonary paracoccidioidomycosis |
author |
Finato, Angela C. [UNESP] |
author_facet |
Finato, Angela C. [UNESP] Almeida, Débora F [UNESP] Dos Santos, Amanda R. [UNESP] Nascimento, Dejair C. Cavalcante, Ricardo S. [UNESP] Mendes, Rinaldo P. [UNESP] Soares, Cléverson T Paniago, Anamaria M M Venturini, James |
author_role |
author |
author2 |
Almeida, Débora F [UNESP] Dos Santos, Amanda R. [UNESP] Nascimento, Dejair C. Cavalcante, Ricardo S. [UNESP] Mendes, Rinaldo P. [UNESP] Soares, Cléverson T Paniago, Anamaria M M Venturini, James |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade Federal de Mato Grosso do Sul (UFMS) Instituto Lauro de Souza Lima (ILSL) |
dc.contributor.author.fl_str_mv |
Finato, Angela C. [UNESP] Almeida, Débora F [UNESP] Dos Santos, Amanda R. [UNESP] Nascimento, Dejair C. Cavalcante, Ricardo S. [UNESP] Mendes, Rinaldo P. [UNESP] Soares, Cléverson T Paniago, Anamaria M M Venturini, James |
dc.subject.por.fl_str_mv |
Paracoccidioides brasiliensis azithromycin cotrimoxazole itraconazole pentoxifylline pulmonary fibrosis thalidomide |
topic |
Paracoccidioides brasiliensis azithromycin cotrimoxazole itraconazole pentoxifylline pulmonary fibrosis thalidomide |
description |
Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the Paracoccidioides genus. Most of the patients with chronic form present sequelae, like pulmonary fibrosis, with no effective treatment, leading to impaired lung functions. In the present study, we aimed to investigate the antifibrotic activity of three compounds: pentoxifylline (PTX), azithromycin (AZT), and thalidomide (Thal) in a murine model of pulmonary PCM treated with itraconazole (ITC) or cotrimoxazole (CMX). BALB/c mice were inoculated with P. brasiliensis (Pb) by the intratracheal route and after 8 weeks, they were submitted to one of the following six treatments: PTX/ITC, PTX/CMX, AZT/ITC, AZT/CMX, Thal/ITC, and Thal/CMX. After 8 weeks of treatment, the lungs were collected for determination of fungal burden, production of OH-proline, deposition of reticulin fibers, and pulmonary concentrations of cytokines and growth factors. Pb-infected mice treated with PTX/ITC presented a reduction in the pulmonary concentrations of OH-proline, associated with lower concentrations of interleukin (IL)-6, IL-17, and transforming growth factor (TGF)-β1 and higher concentrations of IL-10 compared to the controls. The Pb-infected mice treated with AZT/CMX exhibited decreased pulmonary concentrations of OH-proline associated with lower levels of TGF-β1, and higher levels of IL-10 compared controls. The mice treated with ITC/Thal and CMX/Thal showed intense weight loss, increased deposition of reticulin fibers, high pulmonary concentrations of CCL3, IFN-γ and VEGF, and decreased concentrations of IL-6, IL-1β, IL-17, and TGF-β1. In conclusion, our findings reinforce the antifibrotic role of PTX only when associated with ITC, and AZT only when associated with CMX, but Thal did not show any action upon addition. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-12T01:29:58Z 2020-12-12T01:29:58Z 2020-07-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1093/mmy/myz100 Medical mycology, v. 58, n. 5, p. 667-678, 2020. 1460-2709 http://hdl.handle.net/11449/199069 10.1093/mmy/myz100 2-s2.0-85087465833 |
url |
http://dx.doi.org/10.1093/mmy/myz100 http://hdl.handle.net/11449/199069 |
identifier_str_mv |
Medical mycology, v. 58, n. 5, p. 667-678, 2020. 1460-2709 10.1093/mmy/myz100 2-s2.0-85087465833 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Medical mycology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
667-678 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
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UNESP |
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Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1803046849627553792 |