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 Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2021
• End date: July 23, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ana Cristina Breithaupt Faloppa
• Grantee: Marina Vidal dos Santos
• Host 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
• Associated scholarship(s): 21/07455-0 - Study of the therapeutic effects of estradiol and prednisolone on lung of brain dead female rats after ex vivo perfusion, BE.EP.DD

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)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VIDAL-DOS-SANTOS, MARINA; ANUNCIACAO, LUCAS F.; ARMSTRONG-JR, ROBERTO; RICARDO-DA-SILVA, FERNANDA Y.; RAMOS, ISABELLA YUMI TAIRA; CORREIA, CRISTIANO J.; MOREIRA, LUIZ F. P.; LEUVENINK, HENRI G. D.; BREITHAUPT-FALOPPA, ANA C.. 17β-estradiol and methylprednisolone association as a therapeutic option to modulate lung inflammation in brain-dead female rats. FRONTIERS IN IMMUNOLOGY, v. 15, p. 15-pg., 2024-05-03. (21/07455-0, 20/11211-6)

MIOLA, ELIZABETH CRISTINA; RICARDO-DA-SILVA, FERNANDA YAMAMOTO; DE FREITAS, PEDRO LUIZ ZONTA; VIDAL-DOS-SANTOS, MARINA; MOREIRA, LUIZ FELIPE PINHO; BREITHAUPT-FALOPPA, ANA CRISTINA; CORREIA, CRISTIANO DE JESUS. The role of sex hormones in the intestinal injury after brain death using a surgical menopause model in rats. Molecular and Cellular Endocrinology, v. 600, p. 9-pg., 2025-02-20. (21/13020-6, 23/00728-6, 20/11211-6)

DOS SANTOS, MARINA VIDAL; DA ANUNCIACAO, LUCAS FERREIRA; ARMSTRONG, ROBERTO, JR.; RICARDO DA SILVA, FERNANDA YAMAMOTO; DE ASSIS RAMOS, MAYARA MUNHOZ; CORREIA, CRISTIANO DE JESUS; PINHO MOREIRA, LUIZ FELIPE; LEUVENINK, HENRI; BREITHAUPT FALOPPA, ANA CRISTINA. Kidney Release of Inflammatory Mediators Is Modulated by 17BETA-Estradiol Associated With Methylprednisolone After Brain Death in Female Rats. TRANSPLANTATION, v. 106, n. 9, p. 1-pg., 2022-09-01. (20/11211-6)

DA ANUNCIACAO, LUCAS FERREIRA; DE SOUSA, MARCELO NUNES; VIDAL-DOS-SANTOS, MARINA; ARMSTRONG-JR, ROBERTO; PINHO MOREIRA, LUIZ FELIPE; CORREIA, CRISTIANO JESUS; BREITHAUPT-FALOPPA, ANA CRISTINA. Modulatory effects of 17?-estradiol on acute lung inflammation after total occlusion of the descending aorta in male rats. International Immunopharmacology, v. 113, p. 9-pg., 2022-10-14. (21/07455-0, 18/25759-3, 20/11211-6)

DOS SANTOS, MARINA VIDAL; DA ANUNCIACAO, LUCAS FERREIRA; ARMSTRONG, ROBERTO, JR.; RICARDO DA SILVA, FERNANDA YAMAMOTO; DE ASSIS RAMOS, MAYARA MUNHOZ; CORREIA, CRISTIANO DE JESUS; PINHO MOREIRA, LUIZ FELIPE; LEUVENINK, HENRI; BREITHAUPT FALOPPA, ANA CRISTINA. 17beta-Estradiol and Methylprednisolone Associated Treatment Modulates Early and Late Cytokine Release in Lungs From Female Rats Submitted to Brain Death. TRANSPLANTATION, v. 106, n. 9, p. 1-pg., 2022-09-01. (20/11211-6)