Combined Silymarin and Cotrimoxazole Therapy Attenuates Pulmonary Fibrosis in Experimental Paracoccidioidomycosis
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/jof8101010 http://hdl.handle.net/11449/246203 |
Resumo: | Paracoccidioidomycosis (PCM), which mainly affects rural workers, is a systemic mycosis caused by the Paracoccidioides genus that induces pulmonary sequelae in most adult patients, causing serious disability and impairing their quality of life. Silymarin is herbal medicine with an effective antifibrotic activity. Considering that in PCM, antifibrotic treatment is still not available in pulmonary fibrosis, we aimed to evaluate combined silymarin and cotrimoxazole (CMX) therapy via the intratracheal route in BALB/c mice infected with P. brasiliensis yeast. After 12 weeks of treatment, the lungs were collected for the determination of fungal burden, production of OH-proline, deposition of collagen fibers, pulmonary concentrations of cytokines, and expression of fibronectin, α-SMA, MMP-2, MMP-9, and TIMP-2. Spleen cell cultures were also performed. Our results showed that infected mice treated with combined silymarin/CMX showed lower deposition of collagen fibers in the lungs and lower pulmonary concentrations of hydroxyproline than the placebo groups. Decreased levels of TGF-β1 and fibronectin and high levels of MMP-2 and IFN-γ were also observed in this group of mice. Collectively, our findings indicate that the combination of antifungal treatment with silymarin has a potent antifibrotic effect associated with an immunomodulatory effect that potentializes the antifungal immune response. |
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Combined Silymarin and Cotrimoxazole Therapy Attenuates Pulmonary Fibrosis in Experimental Paracoccidioidomycosiscotrimoxazoleparacoccidioidomycosispulmonary fibrosispulmonary sequelaesilymarinParacoccidioidomycosis (PCM), which mainly affects rural workers, is a systemic mycosis caused by the Paracoccidioides genus that induces pulmonary sequelae in most adult patients, causing serious disability and impairing their quality of life. Silymarin is herbal medicine with an effective antifibrotic activity. Considering that in PCM, antifibrotic treatment is still not available in pulmonary fibrosis, we aimed to evaluate combined silymarin and cotrimoxazole (CMX) therapy via the intratracheal route in BALB/c mice infected with P. brasiliensis yeast. After 12 weeks of treatment, the lungs were collected for the determination of fungal burden, production of OH-proline, deposition of collagen fibers, pulmonary concentrations of cytokines, and expression of fibronectin, α-SMA, MMP-2, MMP-9, and TIMP-2. Spleen cell cultures were also performed. Our results showed that infected mice treated with combined silymarin/CMX showed lower deposition of collagen fibers in the lungs and lower pulmonary concentrations of hydroxyproline than the placebo groups. Decreased levels of TGF-β1 and fibronectin and high levels of MMP-2 and IFN-γ were also observed in this group of mice. Collectively, our findings indicate that the combination of antifungal treatment with silymarin has a potent antifibrotic effect associated with an immunomodulatory effect that potentializes the antifungal immune response.Faculdade de Ciências Universidade Estadual Paulista (UNESP), SPFaculdade de Medicina Universidade Estadual Paulista (UNESP), SPFaculdade de Medicina Universidade Federal de Mato Grosso do Sul (UFMS), MSFaculdade de Ciências Universidade Estadual Paulista (UNESP), SPFaculdade de Medicina Universidade Estadual Paulista (UNESP), SPUniversidade Estadual Paulista (UNESP)Universidade Federal de Mato Grosso do Sul (UFMS)Resende, Victor Quinholes [UNESP]Reis-Goes, Karoline Hagata [UNESP]Finato, Angela Carolina [UNESP]de Fátima Almeida-Donanzam, Déborados Santos, Amanda RibeiroPerico, Jonatas [UNESP]Amorim, Barbara CasellaVenturini, James2023-07-29T12:34:25Z2023-07-29T12:34:25Z2022-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/jof8101010Journal of Fungi, v. 8, n. 10, 2022.2309-608Xhttp://hdl.handle.net/11449/24620310.3390/jof81010102-s2.0-85140930702Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Fungiinfo:eu-repo/semantics/openAccess2023-07-29T12:34:25Zoai:repositorio.unesp.br:11449/246203Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:44:49.718770Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Combined Silymarin and Cotrimoxazole Therapy Attenuates Pulmonary Fibrosis in Experimental Paracoccidioidomycosis |
title |
Combined Silymarin and Cotrimoxazole Therapy Attenuates Pulmonary Fibrosis in Experimental Paracoccidioidomycosis |
spellingShingle |
Combined Silymarin and Cotrimoxazole Therapy Attenuates Pulmonary Fibrosis in Experimental Paracoccidioidomycosis Resende, Victor Quinholes [UNESP] cotrimoxazole paracoccidioidomycosis pulmonary fibrosis pulmonary sequelae silymarin |
title_short |
Combined Silymarin and Cotrimoxazole Therapy Attenuates Pulmonary Fibrosis in Experimental Paracoccidioidomycosis |
title_full |
Combined Silymarin and Cotrimoxazole Therapy Attenuates Pulmonary Fibrosis in Experimental Paracoccidioidomycosis |
title_fullStr |
Combined Silymarin and Cotrimoxazole Therapy Attenuates Pulmonary Fibrosis in Experimental Paracoccidioidomycosis |
title_full_unstemmed |
Combined Silymarin and Cotrimoxazole Therapy Attenuates Pulmonary Fibrosis in Experimental Paracoccidioidomycosis |
title_sort |
Combined Silymarin and Cotrimoxazole Therapy Attenuates Pulmonary Fibrosis in Experimental Paracoccidioidomycosis |
author |
Resende, Victor Quinholes [UNESP] |
author_facet |
Resende, Victor Quinholes [UNESP] Reis-Goes, Karoline Hagata [UNESP] Finato, Angela Carolina [UNESP] de Fátima Almeida-Donanzam, Débora dos Santos, Amanda Ribeiro Perico, Jonatas [UNESP] Amorim, Barbara Casella Venturini, James |
author_role |
author |
author2 |
Reis-Goes, Karoline Hagata [UNESP] Finato, Angela Carolina [UNESP] de Fátima Almeida-Donanzam, Débora dos Santos, Amanda Ribeiro Perico, Jonatas [UNESP] Amorim, Barbara Casella Venturini, James |
author2_role |
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) |
dc.contributor.author.fl_str_mv |
Resende, Victor Quinholes [UNESP] Reis-Goes, Karoline Hagata [UNESP] Finato, Angela Carolina [UNESP] de Fátima Almeida-Donanzam, Débora dos Santos, Amanda Ribeiro Perico, Jonatas [UNESP] Amorim, Barbara Casella Venturini, James |
dc.subject.por.fl_str_mv |
cotrimoxazole paracoccidioidomycosis pulmonary fibrosis pulmonary sequelae silymarin |
topic |
cotrimoxazole paracoccidioidomycosis pulmonary fibrosis pulmonary sequelae silymarin |
description |
Paracoccidioidomycosis (PCM), which mainly affects rural workers, is a systemic mycosis caused by the Paracoccidioides genus that induces pulmonary sequelae in most adult patients, causing serious disability and impairing their quality of life. Silymarin is herbal medicine with an effective antifibrotic activity. Considering that in PCM, antifibrotic treatment is still not available in pulmonary fibrosis, we aimed to evaluate combined silymarin and cotrimoxazole (CMX) therapy via the intratracheal route in BALB/c mice infected with P. brasiliensis yeast. After 12 weeks of treatment, the lungs were collected for the determination of fungal burden, production of OH-proline, deposition of collagen fibers, pulmonary concentrations of cytokines, and expression of fibronectin, α-SMA, MMP-2, MMP-9, and TIMP-2. Spleen cell cultures were also performed. Our results showed that infected mice treated with combined silymarin/CMX showed lower deposition of collagen fibers in the lungs and lower pulmonary concentrations of hydroxyproline than the placebo groups. Decreased levels of TGF-β1 and fibronectin and high levels of MMP-2 and IFN-γ were also observed in this group of mice. Collectively, our findings indicate that the combination of antifungal treatment with silymarin has a potent antifibrotic effect associated with an immunomodulatory effect that potentializes the antifungal immune response. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-10-01 2023-07-29T12:34:25Z 2023-07-29T12:34:25Z |
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/10.3390/jof8101010 Journal of Fungi, v. 8, n. 10, 2022. 2309-608X http://hdl.handle.net/11449/246203 10.3390/jof8101010 2-s2.0-85140930702 |
url |
http://dx.doi.org/10.3390/jof8101010 http://hdl.handle.net/11449/246203 |
identifier_str_mv |
Journal of Fungi, v. 8, n. 10, 2022. 2309-608X 10.3390/jof8101010 2-s2.0-85140930702 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Fungi |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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 |
institution |
UNESP |
reponame_str |
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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1808129353787113472 |