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Study of the therapeutic effects of 17beta-estradiol and prednisolone association in pulmonary inflammation on female rats subject to brain death

Grant number: 20/11211-6
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): March 01, 2021
Effective date (End): July 31, 2023
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Ana Cristina Breithaupt Faloppa
Grantee:Marina Vidal dos Santos
Home Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Organ transplantation from Brain Dead (BD) individuals is the possible treatment for many patients in endstage of disease. Several studies highlight the impact of brain death on organ viability. BD leads to a systemic inflammatory process associated with hormonal, metabolic and hemodynamic changes. The lung is one of the organs most affected by brain death. Previous studies of pulmonary inflammation caused by BD, showed a more relevant inflammatory frame in female rats and the worst outcome of lung transplantation with female organs associated with an acute reduction of female sex hormones. The pituitary failure resulting from BD causes the reduction of several other hormones, like glicocorticoids, which compromises the donor's response to the inflammatory process. Female sex hormones and corticosteroids release are related. Female sex hormones regulate corticosteroids levels by blocking the negative feedback of its receptors. Several studies indicate that donor hormonal replacement with corticosteroids after BD contributes to improving the quality of several organs for transplantation, including the lung. In previous studies from our laboratory, estradiol treatment after BD reduced lung inflammation. Thus, the aim of this study is to investigate the combined treatment of estradiol and prednisolone on lung inflammation after BD. We intend to evaluate: (1) leukocyte mobilization from bone marrow to blood and lung; (2) lung microcirculation by intravital microscopy; (3) lung function by spirometry and gas exchange; (4) systemic and local release of inflammatory mediators; (5) lung microvascular permeability and myeloperoxidase activity; (6) expression of adhesion molecules on lung tissue. (AU)

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