Role of acetate in ischemia and reperfusion-induced mitochondrial injury and renal injury

• Grant number: 19/22409-4
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): June 01, 2020
• Effective date (End): January 31, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal researcher: Niels Olsen Saraiva Câmara
• Grantee: João Vitor Ziroldo Lopes
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology, AP.TEM

Abstract

Renal transplantation is one of the main procedures performed in Brazil. Although the country finds itself in a relevant worldwide position, it still finds deficit in this sector: in 2010, from the demand of 11.040 transplants, 4.630 were attended. Beyond the regional disparities in the country, we have negative outcomes around the procedure: the organ goes trough a period of warm ischemia in live donors and deceases ones, and cold ischemia in deceases donors, which leads to dysfunctions in mitochondria and cellular metabolism, causing cell death and decreasing organ viability. Previews studies have proposed mechanisms of analysis and intervention that reduced the phenomena of dysfunction and tissue injury, leading to greater preservation and viability of the graft. Specifically, analysis revealed the role of the gut mycrobiote and its short-chain fatty acid as a possible factor in improving the outcome in transplant, highlighting acetate, that provided a greater protective balance within the analyzed molecules. Our objective, therefore, is to deepen the knowledge e understand the mechanisms of protection e conservation around the acetate, with the mitochondrial dynamics being emphasized, in glucose metabolism and in oxidative stress in general during warm ischemia and, after analysis, during cold ischemia. To do so, we will work with a classic model of ischemia-reperfusion induced renal injuty and cellular biology and molecular methods to respond this objective. We believe that the induction of acetate in those models would be able to attenuate the mitochondrial dysfunction and favor a better graft function (AU)