Banca de QUALIFICAÇÃO: CARLOS ALEXANDRE FALCONI

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : CARLOS ALEXANDRE FALCONI
DATE: 25/09/2023
TIME: 14:00
LOCAL: RNP video conferencia
TITLE:

Effect of the uremic compound P-cresyl sulfate on cardiorenal syndrome type 3.

PAGES: 57
BIG AREA: Ciências Biológicas
AREA: Fisiologia
SUBÁREA: Fisiologia de Órgãos e Sistemas
SPECIALTY: Fisiologia Cardiovascular
SUMMARY:

Renal and cardiac dysfunctions are classified as Cardiorenal Syndrome (SCR), and can be divided into 5 different types (SCR 1 to 5), according to the organ of onset, kidney or heart, and the degree of involvement, acute or chronic. . Patients with kidney diseases show accumulation of substances called “uremic toxins” which, in physiological situations, would be excreted in the urine. These toxins disturb homeostasis, leading to metabolic alterations and the onset of inflammatory conditions. Among these toxins, P-Cresyl Sulfate (PCS) stands out, which has a low molecular weight and high association with serum proteins, making it difficult to remove efficiently by dialytic membranes. Although it is known that kidney injuries can cause cardiac dysfunction, the mechanisms that lead to increased cardiovascular complications due to retention of uremic toxins such as PCS are not completely understood. Thus, the aim of the present study was to evaluate the renocardial effects of treatment with the uremic toxin PCS in animals submitted to acute kidney injury due to ischemia and reperfusion. C57Bl-6 mice submitted to 2 protocols were used: i) treatment with PCS (20 mg/Kg/day) for 15 days and ii) submitted to acute kidney injury due to ischemia (I/R) associated with treatment with PCS. Markers of renal and cardiac injury and systemic and local inflammatory status were evaluated. As a result, we observed that the dose of 20 mg/L of PCS was able to promote a decrease in renal mass, and an increase in the gene expression of Cystatin C and KIM-1 markers in the renal tissue, and a decrease in the marker of cardiac trophism α-actin in the heart. The effect of PCS on AKI was able to increase the gene expression of the renal biomarkers NGAL in the left kidney and Cystatin C in the right kidney. However, the effect of PCS did not potentiate the increase in gene expression and KIM-1 and N-GAL in the left kidney, and Cystatin C in the right kidney. Furthermore, the effect of PCS after AKI was not able to increase the gene expression of the cardiac trophism marker α-actin, and increase the heart/tibia weight ratio observed in the IR. Furthermore, the effect of PCS after AKI was not able to increase the gene expression of the cardiac trophism marker α-actin, and increase the heart/tibia weight ratio observed in the IR. It was possible to observe a decrease in the levels of IL-1β and IL-10 in the group submitted to IR and group submitted to IR + PCS. IL-6 showed an increase in the group submitted to IR, however, treatment with PCS after IR did not potentiate the increase in this inflammatory cytokine. Gene expression of IL-1β and IL-6 in the renal tissue demonstrated that PCS does not potentiate the effect observed in IR. Also, in cardiac tissue, treatment with PCS after IR was not able to increase IL1-β gene expression. Furthermore, we observed the marked decrease of IL-6 in the PCS-treated IR group compared to the IR group. So far, our data suggest a reno and cardioprotective effect of PCS in AKI.

COMMITTEE MEMBERS:
Presidente - Interno ao Programa - 1227329 - CESAR AUGUSTO JOAO RIBEIRO
Membro Titular - Examinador(a) Externo ao Programa - 1600878 - ARNALDO RODRIGUES DOS SANTOS JUNIOR
Membro Titular - Examinador(a) Externo à Instituição - MARIA APARECIDA DALBONI - UNINOVE
Membro Suplente - Examinador(a) Interno ao Programa - 2605490 - SERGIO DAISHI SASAKI