The role of sex hormones in the intestinal injury after brain death using a surgical menopause model in rats

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Cellular Endocrinology; v. 600, p. 9-pg., 2025-02-20.

Resumo

Among transplantable organs, the intestine is one of the most challenging organs to transplant. While there is considerable research on the effects of brain death (BD), little is known about the specific intestinal changes that occur, particularly in females. Here we investigated the role of female sex hormones in the BD-induced intestinal inflammation, using an ovariectomy (OVx) model for sex hormones depletion. Wistar rats (female) were divided into four experimental groups: Control non-OVx - non-manipulated; Control-OVx -ovariectomized; BD non-OVx - animals submitted to BD (6h); BD-OVx -ovariectomized animals submitted to BD. OVx was performed 10 days before BD induction. non-OVx groups were chosen during proestrus phase (heat period). Inflammatory mediators and white blood cell count were quantified in the blood. Intestine tissue was sampled for histopathological analysis, myeloperoxidase (MPO) activity, Evans blue dye extravasation assay and immunohistochemistry. Results show higher intestinal injury in BD-OVx than BD non-OVx animals, presenting reduced crypt depth and increased serum inflammatory mediators. Independently from the previous hormonal status, BD increased intestinal inflammation, with higher leukocyte infiltration, MPO activity, ICAM-1 expression, and higher serum MIP-1 alpha. In summary, BD modulates intestinal inflammation by increasing leukocyte mobilization. Whereas OVx, and its consequences on the female hormonal profile, influences homeostasis and BD-induced inflammation, increasing inflammatory mediators and altering intestinal morphology. (AU)

• Processo FAPESP: 21/13020-6 - Influência do tratamento com estradiol em doadores em morte encefálica na disfunção primária do enxerto pulmonar
• Beneficiário: Fernanda Yamamoto Ricardo da Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 23/00728-6 - Importância dos hormônios sexuais femininos e da menopausa em doadores em morte encefálica: identificação de miRNAs como marcadores de qualidade dos órgãos
• Beneficiário: Ana Cristina Breithaupt Faloppa
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 20/11211-6 - Estudo dos efeitos terapêuticos da associação do 17beta-estradiol e da prednisolona na inflamação pulmonar em ratas submetidas à morte encefálica
• Beneficiário: Marina Vidal dos Santos
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto