Effect of inflammasome inhibitor after experimental brain death: normothermic machine perfusion versus static cold storage of treated kidneys.

• Grant number: 23/08792-5
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2024
• End date: August 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Heloisa Cristina Caldas
• Grantee: Heloisa Cristina Caldas
• 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
• Associated researchers: Ana Cristina Breithaupt Faloppa ; Mario Abbud Filho

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 perfusion machine (NPM). Methods. 56 male rats will be divided into 6 groups: 1) sham (n=6), 2) induction of brain death without treatment (n=10); 3) induction of brain death and in situ perfusion of the kidney without treatment; 4) induction of brain death and in situ perfusion with the administration of MCC950 (n=10); 5) induction of brain death and administration of MCC950 in the perfusion fluid in NPM (n=10), 6) induction of brain death without treatment using NPM (n=10). From the collected kidney samples, gene, and protein expression will be performed using the TaqMan Gene Expression Array Plates system and western blotting, in addition to histological analysis. (AU)