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Gold Nanoparticles Inhibit Steroid-Insensitive Asthma in Mice Preserving Histone Deacetylase 2 and NRF2 Pathways

Background: Gold nanoparticles (AuNPs) can inhibit pivotal pathological changes in experimental asthma, but their effect on steroid-insensitive asthma is unclear. The current study assessed the effectiveness of nebulized AuNPs in a murine model of glucocorticoid (GC)-resistant asthma. Methods: A/J m...

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Autores principales: Serra, Magda F., Cotias, Amanda C., Pimentel, Andreza S., de Arantes, Ana Carolina S., Pires, Ana Lucia A., Lanzetti, Manuella, Hickmann, Jandir M., Barreto, Emiliano, Carvalho, Vinicius F., Silva, Patrícia M. R. e, Cordeiro, Renato S. B., Martins, Marco Aurélio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495660/
https://www.ncbi.nlm.nih.gov/pubmed/36139733
http://dx.doi.org/10.3390/antiox11091659
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author Serra, Magda F.
Cotias, Amanda C.
Pimentel, Andreza S.
de Arantes, Ana Carolina S.
Pires, Ana Lucia A.
Lanzetti, Manuella
Hickmann, Jandir M.
Barreto, Emiliano
Carvalho, Vinicius F.
Silva, Patrícia M. R. e
Cordeiro, Renato S. B.
Martins, Marco Aurélio
author_facet Serra, Magda F.
Cotias, Amanda C.
Pimentel, Andreza S.
de Arantes, Ana Carolina S.
Pires, Ana Lucia A.
Lanzetti, Manuella
Hickmann, Jandir M.
Barreto, Emiliano
Carvalho, Vinicius F.
Silva, Patrícia M. R. e
Cordeiro, Renato S. B.
Martins, Marco Aurélio
author_sort Serra, Magda F.
collection PubMed
description Background: Gold nanoparticles (AuNPs) can inhibit pivotal pathological changes in experimental asthma, but their effect on steroid-insensitive asthma is unclear. The current study assessed the effectiveness of nebulized AuNPs in a murine model of glucocorticoid (GC)-resistant asthma. Methods: A/J mice were sensitized and subjected to intranasal instillations of ovalbumin (OVA) once a week for nine weeks. Two weeks after starting allergen stimulations, mice were subjected to Budesonide or AuNP nebulization 1 h before stimuli. Analyses were carried out 24 h after the last provocation. Results: We found that mice challenged with OVA had airway hyperreactivity, eosinophil, and neutrophil infiltrates in the lung, concomitantly with peribronchiolar fibrosis, mucus production, and pro-inflammatory cytokine generation compared to sham-challenged mice. These changes were inhibited in mice treated with AuNPs, but not Budesonide. In the GC-resistant asthmatic mice, oxidative stress was established, marked by a reduction in nuclear factor erythroid 2-related factor 2 (NRF2) levels and catalase activity, accompanied by elevated values of thiobarbituric acid reactive substances (TBARS), phosphoinositide 3-kinases δ (PI3Kδ) expression, as well as a reduction in the nuclear expression of histone deacetylase 2 (HDAC2) in the lung tissue, all of which sensitive to AuNPs but not Budesonide treatment. Conclusion: These findings suggest that AuNPs can improve GC-insensitive asthma by preserving HDAC2 and NRF2.
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spelling pubmed-94956602022-09-23 Gold Nanoparticles Inhibit Steroid-Insensitive Asthma in Mice Preserving Histone Deacetylase 2 and NRF2 Pathways Serra, Magda F. Cotias, Amanda C. Pimentel, Andreza S. de Arantes, Ana Carolina S. Pires, Ana Lucia A. Lanzetti, Manuella Hickmann, Jandir M. Barreto, Emiliano Carvalho, Vinicius F. Silva, Patrícia M. R. e Cordeiro, Renato S. B. Martins, Marco Aurélio Antioxidants (Basel) Article Background: Gold nanoparticles (AuNPs) can inhibit pivotal pathological changes in experimental asthma, but their effect on steroid-insensitive asthma is unclear. The current study assessed the effectiveness of nebulized AuNPs in a murine model of glucocorticoid (GC)-resistant asthma. Methods: A/J mice were sensitized and subjected to intranasal instillations of ovalbumin (OVA) once a week for nine weeks. Two weeks after starting allergen stimulations, mice were subjected to Budesonide or AuNP nebulization 1 h before stimuli. Analyses were carried out 24 h after the last provocation. Results: We found that mice challenged with OVA had airway hyperreactivity, eosinophil, and neutrophil infiltrates in the lung, concomitantly with peribronchiolar fibrosis, mucus production, and pro-inflammatory cytokine generation compared to sham-challenged mice. These changes were inhibited in mice treated with AuNPs, but not Budesonide. In the GC-resistant asthmatic mice, oxidative stress was established, marked by a reduction in nuclear factor erythroid 2-related factor 2 (NRF2) levels and catalase activity, accompanied by elevated values of thiobarbituric acid reactive substances (TBARS), phosphoinositide 3-kinases δ (PI3Kδ) expression, as well as a reduction in the nuclear expression of histone deacetylase 2 (HDAC2) in the lung tissue, all of which sensitive to AuNPs but not Budesonide treatment. Conclusion: These findings suggest that AuNPs can improve GC-insensitive asthma by preserving HDAC2 and NRF2. MDPI 2022-08-26 /pmc/articles/PMC9495660/ /pubmed/36139733 http://dx.doi.org/10.3390/antiox11091659 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Serra, Magda F.
Cotias, Amanda C.
Pimentel, Andreza S.
de Arantes, Ana Carolina S.
Pires, Ana Lucia A.
Lanzetti, Manuella
Hickmann, Jandir M.
Barreto, Emiliano
Carvalho, Vinicius F.
Silva, Patrícia M. R. e
Cordeiro, Renato S. B.
Martins, Marco Aurélio
Gold Nanoparticles Inhibit Steroid-Insensitive Asthma in Mice Preserving Histone Deacetylase 2 and NRF2 Pathways
title Gold Nanoparticles Inhibit Steroid-Insensitive Asthma in Mice Preserving Histone Deacetylase 2 and NRF2 Pathways
title_full Gold Nanoparticles Inhibit Steroid-Insensitive Asthma in Mice Preserving Histone Deacetylase 2 and NRF2 Pathways
title_fullStr Gold Nanoparticles Inhibit Steroid-Insensitive Asthma in Mice Preserving Histone Deacetylase 2 and NRF2 Pathways
title_full_unstemmed Gold Nanoparticles Inhibit Steroid-Insensitive Asthma in Mice Preserving Histone Deacetylase 2 and NRF2 Pathways
title_short Gold Nanoparticles Inhibit Steroid-Insensitive Asthma in Mice Preserving Histone Deacetylase 2 and NRF2 Pathways
title_sort gold nanoparticles inhibit steroid-insensitive asthma in mice preserving histone deacetylase 2 and nrf2 pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495660/
https://www.ncbi.nlm.nih.gov/pubmed/36139733
http://dx.doi.org/10.3390/antiox11091659
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