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Evaluation of estradiol treatment in brain death donors after lung transplantation: leukocyte mobilization

Grant number: 23/12247-2
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2024
Effective date (End): February 28, 2025
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Fernanda Yamamoto Ricardo da Silva
Grantee:Giovanna Wellichan Vilela Silva
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

Abstract

Organ transplant is one of the main available alternatives for patients that doesn't have other treatment options. When it comes to patients affected by brain death (BD), the systemic inflammation resulting from BD is one of the main conditions that needs to be evaluated, not only in the donor, but also in the receptor. BD leads to a group of metabolic, immunologic and hemodynamic changes, along with systemic inflammation, which affects the organs in different ways. The lung is one of the most fragile organs to this process, and ends up extremely harmed. The influence of grafts and maintenance techniques study is demonstrated by the low number of lung transplants in Brazil, and also by the decreasing percentage of survival of transplanted patients in the years following the procedure. Furthermore, factors such as sexual dimorphism affect the prognosis of the patient. Experimental studies evidence a more severe systemic inflammation in female rats submitted to lung transplant, when compared to female rats previously ovariectomized, and male rats from the same species, leading to the influence of the reduction of female sex hormones (FSH) after BD. Estradiol, one of the female sex hormones of the hypothalamic-pituitary-ovarian (HPO), é often evaluated because of its anti-inflammatory function and its role with differents organs, being used in different research groups, such as hemorrhagic shock, ischemia and sepsis. Therefore, the goal of this present study is to evaluate the effects of the treatment with estradiol in the lung inflammation on rats, female and male, submitted to BD and unilateral lung transplant, exploring (1) leukocytes mobilization in the lung and blood tissue after the transplant, (2) the systemic and local production of inflammatory mediators, and (3) the protein expression of factors related to the inflammatory process in the lung.

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