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

Autor(es)

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

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Lab Cirurgia Cardiovasc & Fisiopatol LIM 11, Inst Coracao InCor, Hosp Clin HCFMUSP, Sao Paulo, SP - Brazil

^[2] Armstrong-Jr, Jr., Roberto, Univ Sao Paulo, Fac Med, Lab Cirurgia Cardiovasc & Fisiopatol LIM 11, Inst Coracao InCor, Hosp Clin HCFMUSP, Sao Paulo, SP - Brazil

^[3] Univ Groningen, Univ Med Ctr Groningen, Dept Surg, Groningen - Netherlands

• Tipo de documento: Artigo Científico
• Fonte: Clinics; v. 76, 2021.
• Citações Web of Science: 0

Resumo

OBJECTIVES: Lung transplantation is limited by the systemic repercussions of brain death (BD). Studies have shown the potential protective role of 17 beta-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 17 beta-estradiol (50 mu g/mL, 2 mL/h) immediately after brain death; and E2-T3, treated with 17 beta-estradiol (50 mu g/ml, 2 ml/h) after 3h of BD. Complement system activity and macrophage presence were analyzed. TNF-alpha, IL-1 beta, 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-alpha and IL-1 beta 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)

• Processo FAPESP: 16/03692-9 - Avaliação do efeito do tratamento com estradiol na inflamação pulmonar em ratas submetidas à morte encefálica
• Beneficiário: Fernanda Yamamoto Ricardo da Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/11798-4 - Influência do estradiol sobre a mobilização leucocitária e a inflamação pulmonar após a morte encefálica
• Beneficiário: Marina Vidal dos Santos
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 18/07289-0 - Avaliação dos efeitos do estradiol em pulmões de ratas em morte encefálica submetidos perfusão ex vivo
• Beneficiário: Fernanda Yamamoto Ricardo da Silva
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado