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

Author(s)

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

• Document type: Journal article
• Source: Molecular and Cellular Endocrinology; v. 600, p. 9-pg., 2025-02-20.

Abstract

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)

• FAPESP's process: 21/13020-6 - INFLUENCE OF BRAIN DEAD DONORS WITH ESTRADIOL TREATMENT ON LUNG PRIMARY GRAFT DYSFUNCTION
• Grantee: Fernanda Yamamoto Ricardo da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 23/00728-6 - Importance of female sex hormones and menopause in brain dead donors: identification of miRNAs as markers of organ quality
• Grantee: Ana Cristina Breithaupt Faloppa
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/11211-6 - Study of the therapeutic effects of 17beta-estradiol and prednisolone association in pulmonary inflammation on female rats subject to brain death
• Grantee: Marina Vidal dos Santos
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)