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

• Grant number: 24/05809-7
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: September 01, 2024
• End date: November 30, 2024
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marcela Sorelli Carneiro Ramos
• Grantee: Beatriz Favero Bedin
• Supervisor: Heidi Noels
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Institution abroad: Uniklinik RWTH Aachen, Germany
• Associated to the scholarship: 23/17588-2 - Effects of uremic toxin p-Cresyl Sulfate on the viability and redox balance of cardiac and renal cells subjected to hypoxia, BP.IC

Abstract

Cardiovascular diseases are the principal cause of death in the world, they can occur for various reasons and can be secondary to other diseases, such as cardiorenal syndromes (CRS). The cardiorenal syndromes are diseases that occur between the kidneys and the heart. Type 3 cardiorenal syndrome, also known as acute renocardiac syndrome, is characterized by acute kidney injury (AKI) which triggers damage to the cardiac tissue. An AKI can arise from a lot of reasons, but the most common in literature is ischemia and reperfusion injury (IR), which is an interruption in the blood supply for an organ followed by the re-stabilization of blood flow with reoxygenation of the organ. An IR causes damage to the tissue, but also activates inflammatory responses, inducing oxidative stress, and increasing cytokines and chemokines liberation. Hypoxia injury is another type of AKI, that is normally associated with IR because of the similarity of the molecular responses in both lesions. The different types of AKI can cause damage to the heart through changes in the immune system, system renin-angiotensin-aldosterone (RAAS), the sympathetic nervous system (SNS), and mitochondrial dysfunction. Another type of renal injury is associated with high levels of uremic compounds, such as p-Cresyl Sulfate (PCS), common in dialysis patients. In physiological situations, these compounds can be eliminated through urine, but in some pathological conditions, they accumulate systemically. Studies have already demonstrated that PCS has negative effects on the kidneys and the heart, and it is associated with a higher mortality rate in patients with chronic kidney disease and undergoing hemodialysis. Considering that: The cellular and molecular mechanisms involved in the development of CRS3 in the presence of PCS and AKI caused by hypoxia are not yet fully understood; and in vitro models can provide a better understanding of the cellular mechanisms involved in cardio/renal axis pathologies. The present study has the objective of evaluating the effect of PCS combined with hypoxia in the production of reactive oxygen species (ROS) in kidney and heart cells, as well as to analyze the effect in ROS production of the conditioned medium by renal cells subjected to hypoxia+PCS on cardiac cells, mimicking SCR3 in vitro. To do so, we will use renal cell culture models (HEK-293) that will be treated with PCS and subjected to hypoxia; subsequently, we will treat cardiomyocytes (H9c2) with the culture medium conditioned by the renal cells previously subjected to PCS and/or hypoxia. The production of ROS will be evaluated by FACS flow cytometry.