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

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 17β-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 μg/ml, 2 ml/h), and E2-T3 (treated with E2 after 3 h of BD; 50 μg/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 RT-PCR and immunohistochemistry, respectively. Release of chemokines and matrix degradation in the lungs were 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 MMP-9 in the lungs. E2 treatment reduced leukocyte infiltration, especially in the E2-T3 group, release of inflammatory mediators, adhesion molecules, and MMP 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.

journal_name

Transplantation

journal_title

Transplantation

authors

Ricardo-da-Silva FY,Armstrong R Jr,Vidal-Dos-Santos M,Correia CJ,Coutinho E Silva RDS,da Anunciação LF,Moreira LFP,Leuvenink HGD,Breithaupt-Faloppa AC

doi

10.1097/TP.0000000000003467

subject

Has Abstract

pub_date

2020-10-07 00:00:00

eissn

0041-1337

issn

1534-6080

pub_type

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