17 beta-Estradiol Treatment Protects Lungs Against Brain Death Effects in Female Rat Donor

Author(s)

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

Affiliation

^[1] Univ Sao Paulo, Inst Coracao InCor, Lab Cirurgia Cardiovasc & Fisiopatol Circulacao L, Fac Med, Sao Paulo - Brazil

^[2] Armstrong Jr, Jr., Roberto, Univ Sao Paulo, Inst Coracao InCor, Lab Cirurgia Cardiovasc & Fisiopatol Circulacao L, Fac Med, Sao Paulo - Brazil

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

• Document type: Journal article
• Source: TRANSPLANTATION; v. 105, n. 4, p. 775-784, APR 2021.
• Web of Science Citations: 1

Abstract

Background. Brain death (BD) affects the viability of lungs for transplantation. A correlation exists between high-lung inflammation after BD and the decrease in female sex hormones, especially estradiol. Therefore, we investigated the effects of 17 beta-estradiol (E2) treatment on the lungs of female brain dead rats. Methods. Female Wistar rats were divided into 4 groups: BD (submitted to BD for 6 h), sham (false operated), E2-T0 (treated with E2 immediately after BD; 50 mu g/mL, 2 mL/h), and E2-T3 (treated with E2 after 3 h of BD; 50 mu g/mL, 2 mL/h). Lung edema, hemorrhage, and leukocyte infiltration were analyzed. Adhesion molecules were evaluated, and analysis of NO synthase gene and protein expression was performed using real-time PCR and immunohistochemistry, respectively. Release of chemokines and matrix degradation in the lungs was analyzed. Results. BD increased leukocyte infiltration, as shown by intravital microscopy (P = 0.017), bronchoalveolar lavage cell count (P = 0.016), the release of inflammatory mediators (P = 0.02), and expression of adhesion molecules. BD also increased microvascular permeability and the expression and activity of matrix metalloproteinase-9 in the lungs. E2 treatment reduced leukocyte infiltration, especially in the E2-T3 group, release of inflammatory mediators, adhesion molecules, and matrix metalloproteinase activity in the lungs. Conclusions. E2 treatment was successful in controlling the lung inflammatory response in females submitted to BD. Our results suggest that E2 directly decreases the release of chemokines, restraining cell traffic into the lungs. Thus, E2 has a therapeutic potential, and its role in improving donor lung quality should be explored further. (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: 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
• 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