Long-term lung inflammation is reduced by estradiol treatment in brain dead female rats.

Autor:	Ricardo-da-Silva FY; Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11), Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR., Armstrong-Jr R; Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11), Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR., Vidal-Dos-Santos M; Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11), Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR., Correia CJ; Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11), Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR., Coutinho E Silva RDS; Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11), Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR., Anunciação LFD; Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11), Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR., Moreira LFP; Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11), Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR., Leuvenink HGD; Department of Surgery, University Medical Centre Groningen, University of Groningen, The Netherlands., Breithaupt-Faloppa AC; Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11), Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR.
Jazyk:	angličtina
Zdroj:	Clinics (Sao Paulo, Brazil) [Clinics (Sao Paulo)] 2021 Aug 16; Vol. 76, pp. e3042. Date of Electronic Publication: 2021 Aug 16 (Print Publication: 2021).
DOI:	10.6061/clinics/2021/e3042
Abstrakt:	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.
Databáze:	MEDLINE
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