Impact of uremic toxin indoxyl sulfate on cardiac cell viability and renal: type 3 cardiorenal syndrome model

• Grant number: 24/08349-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2024
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marcela Sorelli Carneiro Ramos
• Grantee: Giovanna Primo de Freitas
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

The role of uremic toxins in a scenario of kidney injury has already been elucidated in literature demonstrating the effects on different tissues and their influence on inflammatory pathways. Among the various TUs currently known we have Indoxyl Sulfate (IS), a molecule formed from the amino acid tryptophan and which belongs to the class of TUs bound to proteins(PBUTs). The IS formed can accumulate in renal patients, as it is not cleared by the body and in severe cases of uremia, its removal is impaired during dialysis therapy as dialysis membranes do not completely remove this compound. It is already known that the kidney and the heart have a direct functional connection, this interaction is known as Cardiorenal Syndrome (CRS) and is divided into 5 types, differentiated by the organ of origin (heart or kidney) and intensity of the injury (acute or chronic). CRS 3 is characterized by acure kidney injury (AKI), which occurs due to the presence of an inflammatory condition and accumulation of TUs that in turn, it can cause damage to heart tissue. Given the above, the focus of this studyis to evaluate the effects of IS on the viability of cardiac cells exposed to conditioned medium by kidney cells treated with IS. To do so, we will use cell culture models HEK-293 kidney cells treated with IS and subsequently the treatment of H9c2 cardiac cells subjected to the conditioned culture medium of kidney cells treated with IS. It will be heldanalysis of cell viability by MTT and analysis of gene expression markersinflammatory markers and cell apoptosis markers by RT-qPCR. Analysis of variance One-way or two-way ANOVA will be used to compare two or more groupsexperimental tests, followed by Tukey's post hoc test to study multiple comparisons. The number samples (n=3) represents the number of experiments carried out with the treatment in cell cultures. Comparison between groups will be made using the student t-test. For all comparisons will be considered significant at p<0.05.