Effects of uremic toxin p-Cresyl Sulfate on the viability and redox balance of cardiac and renal cells subjected to hypoxia

• Grant number: 23/17588-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2024
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marcela Sorelli Carneiro Ramos
• Grantee: Beatriz Favero Bedin
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated scholarship(s): 24/05809-7 - Effects of the uremic toxin p-Cresyl Sulfate in the oxidative stress of renal and cardiac cells subjected to hypoxia-induced type 3 renocardiac syndrome, BE.EP.IC

Abstract

Cardiovascular diseases (CVD) are the cause of most deaths, due not only to genetic factors, but above all, environmental factors, due to the modern lifestyle. However, they may be secondary to other diseases, such as cardiorenal syndromes (CRSs). Cardiorenal syndromes are diseases that highlight the intense connection between the functioning of the kidneys and the heart and are subdivided into five categories. Type 3 Cardiorenal Syndrome (CRS 3) is characterized by acute kidney injury (AKI) that triggers damage to cardiac tissue. Among AKIs, ischemia and reperfusion injury is very common in hemorrhagic shocks and kidney transplants. Another type of kidney injury is associated with high levels of uremic compounds, such as Indoxyl Sulfate and p-Cresyl Sulfate (PCS), common in dialysis patients. In physiological situations, these compounds can be eliminated through urine, however, in some pathological conditions they accumulate systemically. Studies have already shown that PCS has negative effects on the kidneys and heart, and is associated with a higher mortality rate in patients with chronic kidney disease and on hemodialysis. Considering that: 1) the cellular and molecular mechanisms involved in the development of SCR 3 in the presence of PCS are not yet completely known and 2) in vitro models can provide a better understanding of the cellular mechanisms involved in pathologies of the cardio/renal axis, the present study aims to evaluate the effect of PCS combined with hypoxia, an AKI model, on kidney and heart cells, as well as to evaluate the effect of medium conditioned by kidney cells subjected to hypoxia+PCS, on heart cells, mimicking SCR3 in vitro. To this end, we will use renal cell culture models (HEK-293) that will be treated with PCS and subjected to hypoxia, subsequently, we will carry out the treatment of cardiomyocytes (H9c2) subjected to the culture medium conditioned by renal cells previously subjected to PCS and/ or hypoxia. Molecular parameters related to cell viability will be evaluated, as well as parameters related to the redox balance of these cells.