Long–term lung inflammation is reduced by estradiol treatment in brain dead female rats
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Clinics |
Texto Completo: | https://www.revistas.usp.br/clinics/article/view/212966 |
Resumo: | OBJECTIVES: Lung transplantation is limited by the systemic repercussions of brain death (BD). Studies have shown the potential protective role of 17β-estradiol on the lungs. Here, we aimed to investigate the effect of estradiol on the long-lasting lung inflammatory state to understand a possible therapeutic application in lung donors with BD. METHODS: Female Wistar rats were separated into 3 groups: BD, subjected to brain death (6h); E2-T0, treated with 17β-estradiol (50 μg/mL, 2 mL/h) immediately after brain death; and E2-T3, treated with 17β-estradiol (50 μg/ml, 2 ml/h) after 3h of BD. Complement system activity and macrophage presence were analyzed. TNF-α, IL-1β, IL-10, and IL-6 gene expression (RT-PCR) and levels in 24h lung culture medium were quantified. Finally, analysis of caspase-3 gene and protein expression in the lung was performed. RESULTS: Estradiol reduced complement C3 protein and gene expression. The presence of lung macrophages was not modified by estradiol, but the release of inflammatory mediators was reduced and TNF-α and IL-1β gene expression were reduced in the E2-T3 group. In addition, caspase-3 protein expression was reduced by estradiol in the same group. CONCLUSIONS: Brain death-induced lung inflammation in females is modulated by estradiol treatment. Study data suggest that estradiol can control the inflammatory response by modulating the release of mediators after brain death in the long term. These results strengthen the idea of estradiol as a therapy for donor lungs and improving transplant outcomes. |
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oai:revistas.usp.br:article/212966 |
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USP-19 |
network_name_str |
Clinics |
repository_id_str |
|
spelling |
Long–term lung inflammation is reduced by estradiol treatment in brain dead female ratsBrain DeathOrgan DonorLung InflammationEstradiolFemale RatsOBJECTIVES: Lung transplantation is limited by the systemic repercussions of brain death (BD). Studies have shown the potential protective role of 17β-estradiol on the lungs. Here, we aimed to investigate the effect of estradiol on the long-lasting lung inflammatory state to understand a possible therapeutic application in lung donors with BD. METHODS: Female Wistar rats were separated into 3 groups: BD, subjected to brain death (6h); E2-T0, treated with 17β-estradiol (50 μg/mL, 2 mL/h) immediately after brain death; and E2-T3, treated with 17β-estradiol (50 μg/ml, 2 ml/h) after 3h of BD. Complement system activity and macrophage presence were analyzed. TNF-α, IL-1β, IL-10, and IL-6 gene expression (RT-PCR) and levels in 24h lung culture medium were quantified. Finally, analysis of caspase-3 gene and protein expression in the lung was performed. RESULTS: Estradiol reduced complement C3 protein and gene expression. The presence of lung macrophages was not modified by estradiol, but the release of inflammatory mediators was reduced and TNF-α and IL-1β gene expression were reduced in the E2-T3 group. In addition, caspase-3 protein expression was reduced by estradiol in the same group. CONCLUSIONS: Brain death-induced lung inflammation in females is modulated by estradiol treatment. Study data suggest that estradiol can control the inflammatory response by modulating the release of mediators after brain death in the long term. These results strengthen the idea of estradiol as a therapy for donor lungs and improving transplant outcomes.Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo2021-08-16info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/clinics/article/view/21296610.6061/clinics/2021/e3042Clinics; Vol. 76 (2021); e3042Clinics; v. 76 (2021); e3042Clinics; Vol. 76 (2021); e30421980-53221807-5932reponame:Clinicsinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/clinics/article/view/212966/194996Copyright (c) 2023 Clinicsinfo:eu-repo/semantics/openAccessRicardo-da-Silva, Fernanda YamamotoArmstrong-Jr, RobertoVidal-dos-Santos, MarinaCorreia, Cristiano de JesusCoutinho e Silva, Raphael dos SantosAnunciação, Lucas Ferreira daMoreira, Luiz Felipe PinhoLeuvenink, Henri Gerrit DerkBreithaupt-Faloppa, Ana Cristina2023-07-06T13:04:06Zoai:revistas.usp.br:article/212966Revistahttps://www.revistas.usp.br/clinicsPUBhttps://www.revistas.usp.br/clinics/oai||clinics@hc.fm.usp.br1980-53221807-5932opendoar:2023-07-06T13:04:06Clinics - Universidade de São Paulo (USP)false |
dc.title.none.fl_str_mv |
Long–term lung inflammation is reduced by estradiol treatment in brain dead female rats |
title |
Long–term lung inflammation is reduced by estradiol treatment in brain dead female rats |
spellingShingle |
Long–term lung inflammation is reduced by estradiol treatment in brain dead female rats Ricardo-da-Silva, Fernanda Yamamoto Brain Death Organ Donor Lung Inflammation Estradiol Female Rats |
title_short |
Long–term lung inflammation is reduced by estradiol treatment in brain dead female rats |
title_full |
Long–term lung inflammation is reduced by estradiol treatment in brain dead female rats |
title_fullStr |
Long–term lung inflammation is reduced by estradiol treatment in brain dead female rats |
title_full_unstemmed |
Long–term lung inflammation is reduced by estradiol treatment in brain dead female rats |
title_sort |
Long–term lung inflammation is reduced by estradiol treatment in brain dead female rats |
author |
Ricardo-da-Silva, Fernanda Yamamoto |
author_facet |
Ricardo-da-Silva, Fernanda Yamamoto Armstrong-Jr, Roberto Vidal-dos-Santos, Marina Correia, Cristiano de Jesus Coutinho e Silva, Raphael dos Santos Anunciação, Lucas Ferreira da Moreira, Luiz Felipe Pinho Leuvenink, Henri Gerrit Derk Breithaupt-Faloppa, Ana Cristina |
author_role |
author |
author2 |
Armstrong-Jr, Roberto Vidal-dos-Santos, Marina Correia, Cristiano de Jesus Coutinho e Silva, Raphael dos Santos Anunciação, Lucas Ferreira da Moreira, Luiz Felipe Pinho Leuvenink, Henri Gerrit Derk Breithaupt-Faloppa, Ana Cristina |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Ricardo-da-Silva, Fernanda Yamamoto Armstrong-Jr, Roberto Vidal-dos-Santos, Marina Correia, Cristiano de Jesus Coutinho e Silva, Raphael dos Santos Anunciação, Lucas Ferreira da Moreira, Luiz Felipe Pinho Leuvenink, Henri Gerrit Derk Breithaupt-Faloppa, Ana Cristina |
dc.subject.por.fl_str_mv |
Brain Death Organ Donor Lung Inflammation Estradiol Female Rats |
topic |
Brain Death Organ Donor Lung Inflammation Estradiol Female Rats |
description |
OBJECTIVES: Lung transplantation is limited by the systemic repercussions of brain death (BD). Studies have shown the potential protective role of 17β-estradiol on the lungs. Here, we aimed to investigate the effect of estradiol on the long-lasting lung inflammatory state to understand a possible therapeutic application in lung donors with BD. METHODS: Female Wistar rats were separated into 3 groups: BD, subjected to brain death (6h); E2-T0, treated with 17β-estradiol (50 μg/mL, 2 mL/h) immediately after brain death; and E2-T3, treated with 17β-estradiol (50 μg/ml, 2 ml/h) after 3h of BD. Complement system activity and macrophage presence were analyzed. TNF-α, IL-1β, IL-10, and IL-6 gene expression (RT-PCR) and levels in 24h lung culture medium were quantified. Finally, analysis of caspase-3 gene and protein expression in the lung was performed. RESULTS: Estradiol reduced complement C3 protein and gene expression. The presence of lung macrophages was not modified by estradiol, but the release of inflammatory mediators was reduced and TNF-α and IL-1β gene expression were reduced in the E2-T3 group. In addition, caspase-3 protein expression was reduced by estradiol in the same group. CONCLUSIONS: Brain death-induced lung inflammation in females is modulated by estradiol treatment. Study data suggest that estradiol can control the inflammatory response by modulating the release of mediators after brain death in the long term. These results strengthen the idea of estradiol as a therapy for donor lungs and improving transplant outcomes. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-08-16 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://www.revistas.usp.br/clinics/article/view/212966 10.6061/clinics/2021/e3042 |
url |
https://www.revistas.usp.br/clinics/article/view/212966 |
identifier_str_mv |
10.6061/clinics/2021/e3042 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
https://www.revistas.usp.br/clinics/article/view/212966/194996 |
dc.rights.driver.fl_str_mv |
Copyright (c) 2023 Clinics info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Copyright (c) 2023 Clinics |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo |
publisher.none.fl_str_mv |
Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo |
dc.source.none.fl_str_mv |
Clinics; Vol. 76 (2021); e3042 Clinics; v. 76 (2021); e3042 Clinics; Vol. 76 (2021); e3042 1980-5322 1807-5932 reponame:Clinics instname:Universidade de São Paulo (USP) instacron:USP |
instname_str |
Universidade de São Paulo (USP) |
instacron_str |
USP |
institution |
USP |
reponame_str |
Clinics |
collection |
Clinics |
repository.name.fl_str_mv |
Clinics - Universidade de São Paulo (USP) |
repository.mail.fl_str_mv |
||clinics@hc.fm.usp.br |
_version_ |
1800222766155169792 |