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

Author(s)

Fernanda Yamamoto Ricardo-da-Silva ^[1] ; Roberto Armstrong-Jr ^[2] ; Marina Vidal-dos-Santos ^[3] ; Cristiano de Jesus Correia ^[4] ; Raphael dos Santos Coutinho e Silva ^[5] ; Lucas Ferreira da Anunciação ^[6] ; Luiz Felipe Pinho Moreira ^[7] ; Henri Gerrit Derk Leuvenink ^[8] ; Ana Cristina Breithaupt-Faloppa ^[9]

Affiliation

^[1] Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo. Instituto do Coracao (InCor). Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11) - Brasil

^[2] Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo. Instituto do Coracao (InCor). Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11) - Brasil

^[3] Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo. Instituto do Coracao (InCor). Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11) - Brasil

^[4] Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo. Instituto do Coracao (InCor). Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11) - Brasil

^[5] Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo. Instituto do Coracao (InCor). Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11) - Brasil

^[6] Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo. Instituto do Coracao (InCor). Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11) - Brasil

^[7] Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo. Instituto do Coracao (InCor). Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11) - Brasil

^[8] University of Groningen. University Medical Centre Groningen. Department of Surgery

^[9] Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo. Instituto do Coracao (InCor). Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11) - Brasil

• Document type: Journal article
• Source: Clinics; v. 76, 2021-08-16.

Abstract

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. (AU)

• FAPESP's process: 17/11798-4 - Estradiol influence on leukocyte mobilization and pulmonary inflammation after brain death
• Grantee: Marina Vidal dos Santos
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 16/03692-9 - Evaluation of the estradiol treatment on pulmonary inflammaton on female rats subject to brain death
• Grantee: Fernanda Yamamoto Ricardo da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/07289-0 - Evaluation of estradiol effects on lung of brain dead female rats after ex vivo perfusion
• Grantee: Fernanda Yamamoto Ricardo da Silva
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate