17 beta-Estradiol protects against lung injuries after brain death in male rats

Autor(es)

Vieira, Roberta Figueiredo ^[1] ; Breithaupt-Faloppa, Ana Cristina ^[1] ; Matsubara, Bruno Carvalho ^[1] ; Rodrigues, Geovana ^[1] ; Sanches, Marcelo Petrof ^[1] ; Armstrong-, Jr., Roberto ^[1] ; Ferreira, Sueli Gomes ^[1] ; Correia, Cristiano de Jesus ^[1] ; Moreira, Luiz Felipe P. ^[1] ; Sannomiya, Paulina ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Lab Cirurg Pesquisa Cardiovasc, Inst Coracao, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF HEART AND LUNG TRANSPLANTATION; v. 37, n. 11, p. 1381-1387, NOV 2018.
• Citações Web of Science: 1

Resumo

BACKGROUND: Brain death elicits microvascular dysfunction and inflammation, and thereby compromises lung viability for transplantation. As 17 beta-estradiol was shown to be anti-inflammatory and vascular protective, we investigated its effects on lung injury after brain death in male rats. METHODS: Wistar rats were assigned to: sham-operation by trepanation only (SH, n = 7); brain death (BD, n = 7); administration of 17-estradiol (280 tg/kg, iv) at 60 minutes after brain death (BD-E2, n = 7). Experiments were performed 180 minutes thereafter. Histopathological changes in the lung were evaluated by histomorphometry. Gene expression of inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and endothelin-1 was measured by real-time polymerise chain reaction. Protein expression of NO synthases, endothelin-1, platelet endothelial cell adhesion molecule-1 (PECAM-1), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), BCL-2, and caspase 3 was assessed by immunohistochemistry. Cytokines were quantified by enzyme linked immunosorbent assay. RESULTS: Treatment with 17P-estradiol after brain death decreased lung edema and hemorrhage (p < 0.0001), and serum levels of cytokine-induced neutrophil chemoattractant-1 (CINC-1; p = 0.0020). iNOS (p < 0.0001) and VCAM-1 (p < 0.0001) also diminished at protein levels, while eNOS accumulated (p = 0.0002). However, gene expression of iNOS, eNOS, and endothelin-1 was comparable among groups, as was protein expression of endothelin-1, ICAM-1, BCL-2, and caspase 3. CONCLUSIONS: 17P-Estradiol effectively reduces lung injury in brain-dead rats mainly due to its ability to regulate NO synthases. Thus, the drug may improve lung viability for transplantation. J Heart Lung Transplant 2018;37:1381-1387 (C) 2018 International Society for Heart and Lung Transplantation. All rights reserved. (AU)

• Processo FAPESP: 16/13632-3 - AVALIAÇÃO DOS EFEITOS DO 17beta-ESTRADIOL SOBRE AS ALTERAÇÕES MICROCIRCULATÓRIAS INDUZIDAS PELA MORTE ENCEFÁLICA EM RATOS MACHOS
• Beneficiário: Paulina Sannomiya
• Modalidade de apoio: Auxílio à Pesquisa - Regular