#2711 Cardiomyocytes exposed to medium conditioned by kidney cells treated with the uremic toxin p-cresyl sulfate undergo changes in cell viability

Abstract

Abstract Background and Aims Cardiorenal Syndrome (CRS) is a condition involving the heart and the kidneys, where a disturbance in one of these organs can lead to alterations in the other. High levels of uremic toxins (UTs) such as p-Cresyl Sulfate (PCS) can induce renal injury. Furthermore, UTs play a crucial role in inflammatory status and cardiac function. Therefore, it is crucial that studies regarding the influence of uremic toxins in the context of cardiorenal syndrome be conducted. Nevertheless, few studies have been conducted in the context of Acute Kidney Injury (AKI) causing acute damage to the heart, and few mechanisms are still known. The objective of the study was to evaluate the role of PCS in cell viability and inflammatory genes in renal and cardiac cells, to simulate cardiorenal syndrome due to excessive PCS. Method The HEK293 (human epithelial renal cells) and H9c2 (murine cardiomyocyte cells) cell lines were used. HEK293 was treated with concentrations of 0.25 mM, 0.5 mM, 1 mM, and 1.5 mM PCS for 6, 24, and 48 hours. H9c2 was treated with PCS (1.5 mM) and conditioned media from PCS-treated renal cells (1.5 mM) for 6 and 24 hours. MTT assays, growth curve analysis, and Hoechst-PI staining were performed. Gene expression was evaluated by RT-qPCR. ANOVA followed by Bonferroni post-test was conducted, considering P < 0.05 as significant. Results PCS treatment led to a time and dose-dependent decrease in cell viability. The cell growth curve indicated a negative impact across time on renal cell proliferation at all different PCS concentrations. Hoechst-PI assay revealed increased cell death in the treatment with PCS (1.5 mM) for 24 hours. There was no change in the gene expression of IL-6, IL-1β, Bax, and Bcl-2 in renal cells. Cardiac cell viability decreased both after direct PCS treatment (85.3%) and exposure to PCS-conditioned media from renal cells for 24 hours (87.3%). Conclusion PCS reduces renal cell viability and inhibits cell proliferation without affecting the inflammatory status and apoptosis signaling within the evaluated time frames. Cardiac cell viability decreased after PCS treatment, either directly or indirectly, suggesting a cardiotoxic effect of PCS, independent of changes in renal cells.