Kidney release of inflammatory mediators is modulated by 17beta-estradiol associated with methylprednisolone after brain death in female rats
Marina Vidal dos Santos1,2, Lucas Ferreira da Anunciação1, Roberto Armstrong Jr1, Fernanda Yamamoto Ricardo da Silva1, Mayara Munhoz de Assis Ramos1, Cristiano de Jesus Correia1, Luiz Felipe Pinho Moreira1, Henri Leuvenink2, Ana Cristina Breithaupt Faloppa1.
1Cardiopneumology , InCor, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), São Paulo, Brazil; 2Surgery, University Medical Centre Groningen, Groningen, Netherlands
Introduction: Brain dead donors are an important source of organs for transplantation. Brain death (BD) triggers systemic alterations and these patients present higher inflammatory profile in comparison to other types of donors. Also, organs from females patients present worse prognostic in comparison to male organs. This scenario is associated with increased inflammation due to acute reduction of females sex hormones after BD, especially estradiol (E2). In females, evidences suggest that the presence of both E2 and corticoids hormones is important to ensure an adequate response to inflammation. The aim of this study is to evaluate the associated treatment of E2 and methylprednisolone (MP) in female rats after BD.
Methods: Female Wistar rats were submitted to BD by rapid inflation of an intracranial balloon catheter and maintained for 6h. Rats received MP (MP, 4 mg/ml i.v–2 ml/h) or MP and E2 (MP/E2, 50 ug/ml) after 3h of BD until the end of experiment. Sham-operated (S) rats were used as controls. After 6h, kidney samples were collected for tissue homogenate and relative gene expression analyzes. IL-1β, IL-6, IL-10, VEGF and TNF- α were quantified in tissue homogenate. Gene expression of IL-1β, IL-6, IL-10, TNF- α and KIM-1 was also evaluated.
Results: In kidney tissue homogenate, IL-6 (p=0.0076) and VEGF (p=0.0241) were increased after BD, and both molecules were reduced after the treatments. Regarding IL-10 (p=0.0624) and TNF-α (p=0.0255), there was no difference between S and BD groups, but there is a significant reduction in both treatments. There were no differences in IL-1β. Regarding relative gene expression, there were no differences among groups in any of the molecules analized.
Conclusion: Our data pointed that, after BD, females rats presented higher inflammation in the kidney in comparison to Sham animals, represented by an increase in tissue release of cytokines, especially IL-6. Results suggest that both treatments are able to reduce kidney acute inflammation. These data propose that corticotherapy and its association with E2 has a potential benefic effect in inflammation triggered by BD in kidneys from females donor, suggesting that this treatment may improve organ quality.
This study was financed by 2020/11211-6, Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP.
