Evaluation of progesterone treatment effects on mesenteric and intestinal changes in an experimental model of ischemia and reperfusion by aortic oclusion in male rats

• Grant number: 21/05673-0
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2022
• End date: February 29, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Cristiano de Jesus Correia
• Grantee: Cristiano de Jesus Correia
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Ana Cristina Breithaupt Faloppa ; Luiz Felipe Pinho Moreira
• Associated research grant(s): 25/05534-0 - Tthe 22nd Congress of the European Society for Organ Transplantation - ESOT 2025, AR.EXT

Abstract

Ischemia is characterized by a generalized reduction in blood flow as well as to a specific area or organ, leading to a decrease in oxygen and nutrient supply, triggering the inflammatory process and causing cell death. For the reversal of the ischemic picture, circulation restoration is essential, but flow restoration, despite preventing cell death, is responsible for aggravating the damage already established during ischemia, causing systemic dissemination of toxic products generated during the tissue reperfusion phase. Among the organs of the gastrointestinal system, the intestine is possibly the most sensitive by the amount of labile cells easily damaged by episodes of ischemia. Particularly, Enteric Nervous System neurons are especially sensitive and can be irreversibly compromised. Several clinical and experimental studies suggest that sex hormones intervene in the course of the inflammatory lesion. Studies conducted in recent years indicate that the response to shock, trauma and sepsis may differ between males and females, finding that females are more resilient than males. Thus, the objective of this project will be to investigate the effect of progesterone treatment on mesenteric lesion in the rat aortic ischemia and reperfusion model. Therefore, we plan to investigate: (1) microvessel perfusion, leukocyte-endothelium interactions and adhesion molecule expression in mesenteric microcirculation; (2) to determine myeloperoxidase activity and microvascular permeability in the intestine; (3) to determine functional and inflammatory bowel changes; (4) to investigate the protein and gene expression of nitric oxide synthase isoforms (iNOS and eNOS) and endothelin in the mesentery vessels; (5) to determine the plasma concentration of cytokines; (6) to evaluate the leukogram, hemodynamic and gasometric parameters; (7) to determine the progesterone plasma concentration. (AU)