Effect of inflammasome inhibitor on rat kidneys after brain death: cold storage versus normothermic machine perfusion.

• Grant number: 23/17655-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 05, 2024
• End date: August 04, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Mario Abbud Filho
• Grantee: Ludimila Leite Marzochi
• Supervisor: Hendrik Gerrit Derk Leuvenink
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil
• Institution abroad: University Medical Center Groningen (UMCG), Netherlands
• Associated to the scholarship: 23/03915-1 - Effect of inflammasome inhibitor on rat kidneys after brain death: cold storage versus normothermic machine perfusion., BP.DR

Abstract

Introduction: The brain death process stimulates systemic inflammation with consequent activation of inflammatory pathways in organs donated for transplants. The combination of prolonged cold ischemia time and brain death induced inflammation is crucial for activating kidneys' innate immunity and pro-inflammatory mechanisms. The inflammasome is one of the most expressed molecules during this process. Thus, its blockade could reduce the innate inflammatory response, minimizing sterile inflammation, improving the quality of "non-ideal" kidneys, and reducing the discard rates of these organs. Objective: Evaluate the effect of administration of the NLRP3 inflammasome inhibitor (MCC950) on gene and protein expression related to innate immunity and sterile inflammation, in rat kidneys, after the brain death process with in situ perfusion or normothermic machine perfusion (NMP). Methods. 40 male rats will be divided into 5 groups: 1) sham (n=8), 2) Non-treated group - 16h Cold Storage (CS) (n=8); 3) Treated group - CS and perfusion in situ with MCC950 (n=8); 4) Non-treated group - CS + NMP (n=8); 5) Treated group - CS + NMP (n=8). From the collected kidney samples, gene, and protein expression will be performed using the TaqMan Gene Expression Array Plates system and immunohistochemistry, in addition to histological analysis.