LASSBio-897 Reduces Lung Injury Induced by Silica Particles in Mice: Potential Interaction with the A2AReceptor
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2017 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/24883 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ. Brasil. |
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Carvalho, Vinicius F.Ferreira, Tatiana P. T.Arantes, Ana C. S. deNoël, FrançoisTesch, RobertaSant'Anna, Carlos M. R.Barreiro, Eliezer J. L.Fraga, Carlos A. M.Silva, Patrícia M. Rodrigues eMartins, Marco A.2018-02-20T14:27:07Z2018-02-20T14:27:07Z2017CARVALHO, Vinicius F. et al. LASSBio-897 Reduces Lung Injury Induced by Silica Particles in Mice: Potential Interaction with the A2A Receptor. Frontiers in Pharmacology, v.8, Article 778, 16p, Oct. 2017.1663-9812https://www.arca.fiocruz.br/handle/icict/2488310.3389/fphar.2017.00778engFrontiers MediaFibroseSilicoseDoença pulmonarA2A receptorcAMPfibrosisLASSBio-897silicosispulmonary diseaseLASSBio-897 Reduces Lung Injury Induced by Silica Particles in Mice: Potential Interaction with the A2AReceptorinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação 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.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio de Janeiro.Instituto de Ciências Biomédicas. Laboratório de Farmacologia Bioquímica e Molecular. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Programa de Pós-Graduação em Farmacologia e Química Medicinal. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Programa de Pós-Graduação em Farmacologia e Química Medicinal. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Laboratório de Avaliação e Síntese de Substâncias Bioativas. Rio de Janeiro, RJ, Brasil.Universidade Federal Rural do Rio de Janeiro. Instituto de Ciências Exatas. Departamento de Química. Seropédica, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Programa de Pós-Graduação em Farmacologia e Química Medicinal. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Laboratório de Avaliação e Síntese de Substâncias Bioativas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Programa de Pós-Graduação em Farmacologia e Química Medicinal. 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. Instituto de Ciências Biomédicas. Programa de Pós-Graduação em Farmacologia e Química Medicinal. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ. Brasil / Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Programa de Pós-Graduação em Farmacologia e Química Medicinal. Rio de Janeiro, RJ, BrasilSilicosis is a lethal fibro-granulomatous pulmonary disease highly prevalent in developing countries, for which no proper therapy is available. Among a small series ofN-acylhydrazones, the safrole-derived compound LASSBio-897 (3-thienylidene-3, 4-methylenedioxybenzoylhydrazide) raised interest due to its ability to bind to the adenosine A2Areceptor. Here, we evaluated the anti-inflammatory and anti-fibrotic potential of LASSBio-897, exploring translation to a mouse model of silicosis and the A2Areceptor as a site of action. Pulmonary mechanics, inflammatory, and fibrotic changes were assessed 28 days after intranasal instillation of silica particles in Swiss-Webster mice. Glosensor cAMP HEK293G cells, CHO cells stably expressing human adenosine receptors and ligand binding assay were used to evaluate the pharmacological properties of LASSBio-897in vitro. Molecular docking studies of LASSBio-897 were performed using the genetic algorithm software GOLD 5.2. We found that the interventional treatment with the A2Areceptor agonist CGS 21680 reversed silica particle-induced airway hyper-reactivity as revealed by increased responses of airway resistance and lung elastance following aerosolized methacholine. LASSBio-897 (2 and 5 mg/kg, oral) similarly reversed pivotal lung pathological features of silicosis in this model, reducing levels of airway resistance and lung elastance, granuloma formation and collagen deposition. In competition assays, LASSBio-897 decreased the binding of the selective A2Areceptor agonist [3H]-CGS21680 (IC50= 9.3 μM). LASSBio-897 (50 μM) induced modest cAMP production in HEK293G cells, but it clearly synergized the cAMP production by adenosine in a mechanism sensitive to the A2Aantagonist SCH 58261. This synergism was also seen in CHO cells expressing the A2A, but not those expressing A2B, A1or A3receptors. Based on the evidence that LASSBio-897 binds to A2Areceptor, molecular docking studies were performed using the A2Areceptor crystal structure and revealed possible binding modes of LASSBio-897 at the orthosteric and allosteric sites. These findings highlight LASSBio-897 as a lead compound in drug development for silicosis, emphasizing the role of the A2Areceptor as its putative site of action.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/24883/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALvinicius_carvalho_etal_IOC_2017.pdfvinicius_carvalho_etal_IOC_2017.pdfapplication/pdf7103934https://www.arca.fiocruz.br/bitstream/icict/24883/2/vinicius_carvalho_etal_IOC_2017.pdf688881add5246bde7ac6c92805d1c591MD52TEXTvinicius_carvalho_etal_IOC_2017.pdf.txtvinicius_carvalho_etal_IOC_2017.pdf.txtExtracted texttext/plain74340https://www.arca.fiocruz.br/bitstream/icict/24883/3/vinicius_carvalho_etal_IOC_2017.pdf.txt76e340429921d0eb3062c393731edb1dMD53icict/248832018-08-15 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| dc.title.pt_BR.fl_str_mv |
LASSBio-897 Reduces Lung Injury Induced by Silica Particles in Mice: Potential Interaction with the A2AReceptor |
| title |
LASSBio-897 Reduces Lung Injury Induced by Silica Particles in Mice: Potential Interaction with the A2AReceptor |
| spellingShingle |
LASSBio-897 Reduces Lung Injury Induced by Silica Particles in Mice: Potential Interaction with the A2AReceptor Carvalho, Vinicius F. Fibrose Silicose Doença pulmonar A2A receptor cAMP fibrosis LASSBio-897 silicosis pulmonary disease |
| title_short |
LASSBio-897 Reduces Lung Injury Induced by Silica Particles in Mice: Potential Interaction with the A2AReceptor |
| title_full |
LASSBio-897 Reduces Lung Injury Induced by Silica Particles in Mice: Potential Interaction with the A2AReceptor |
| title_fullStr |
LASSBio-897 Reduces Lung Injury Induced by Silica Particles in Mice: Potential Interaction with the A2AReceptor |
| title_full_unstemmed |
LASSBio-897 Reduces Lung Injury Induced by Silica Particles in Mice: Potential Interaction with the A2AReceptor |
| title_sort |
LASSBio-897 Reduces Lung Injury Induced by Silica Particles in Mice: Potential Interaction with the A2AReceptor |
| author |
Carvalho, Vinicius F. |
| author_facet |
Carvalho, Vinicius F. Ferreira, Tatiana P. T. Arantes, Ana C. S. de Noël, François Tesch, Roberta Sant'Anna, Carlos M. R. Barreiro, Eliezer J. L. Fraga, Carlos A. M. Silva, Patrícia M. Rodrigues e Martins, Marco A. |
| author_role |
author |
| author2 |
Ferreira, Tatiana P. T. Arantes, Ana C. S. de Noël, François Tesch, Roberta Sant'Anna, Carlos M. R. Barreiro, Eliezer J. L. Fraga, Carlos A. M. Silva, Patrícia M. Rodrigues e Martins, Marco A. |
| author2_role |
author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Carvalho, Vinicius F. Ferreira, Tatiana P. T. Arantes, Ana C. S. de Noël, François Tesch, Roberta Sant'Anna, Carlos M. R. Barreiro, Eliezer J. L. Fraga, Carlos A. M. Silva, Patrícia M. Rodrigues e Martins, Marco A. |
| dc.subject.other.pt_BR.fl_str_mv |
Fibrose Silicose Doença pulmonar |
| topic |
Fibrose Silicose Doença pulmonar A2A receptor cAMP fibrosis LASSBio-897 silicosis pulmonary disease |
| dc.subject.en.pt_BR.fl_str_mv |
A2A receptor cAMP fibrosis LASSBio-897 silicosis pulmonary disease |
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Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ. Brasil. |
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2017 |
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2017 |
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2018-02-20T14:27:07Z |
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2018-02-20T14:27:07Z |
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info:eu-repo/semantics/article |
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article |
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CARVALHO, Vinicius F. et al. LASSBio-897 Reduces Lung Injury Induced by Silica Particles in Mice: Potential Interaction with the A2A Receptor. Frontiers in Pharmacology, v.8, Article 778, 16p, Oct. 2017. |
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https://www.arca.fiocruz.br/handle/icict/24883 |
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1663-9812 |
| dc.identifier.doi.none.fl_str_mv |
10.3389/fphar.2017.00778 |
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CARVALHO, Vinicius F. et al. LASSBio-897 Reduces Lung Injury Induced by Silica Particles in Mice: Potential Interaction with the A2A Receptor. Frontiers in Pharmacology, v.8, Article 778, 16p, Oct. 2017. 1663-9812 10.3389/fphar.2017.00778 |
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