Effect of p-cresyl sulfate (PCS) on components of purinergic signaling in the mouse aorta

• Grant number: 22/13140-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2023
• End date: December 31, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Cristina Ribas Fürstenau
• Grantee: Victor da Silva Jacyntho
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Uremic toxins are organic solutes resulting from the fermentation of proteins from the diet and from the action of bacterial enzymes present in the gut microbiota. In the liver, the uremic toxin p-cresol is sulfated to form p-cresyl sulfate (PCS), which is excreted in the urine or feces under normal conditions. In dialysis patients, the serum concentration of PCS is 17 times higher than in healthy individuals, as only 30% of the solute is removed in the process of hemodialysis. The accumulation of p-cresyl impacts several organs and systems, including the vasculature, as it acts as a pro-oxidant on vascular smooth muscle cells. The purinergic signaling plays an important role in controlling vascular functions, such as vasomotor responses and inflammation. Taking into consideration the recognized vascular effects of PCS and the importance of purinergic signaling in blood vessels, the hypothesis of this work is that the accumulation of p-cresyl sulfate in plasma can lead to uremia, which may further cause dysregulation of the purinergic system in the mouse aorta, potentiating the damage caused by this uremic toxin. In this study, we will evaluate the possible modulatory effects of the uremic compound PCS in the aorta of mice, focusing on the main components of signaling purinergic (purinoceptors and ectonucleotidases), in addition to inflammatory markers and indicators of kidney damage. After PCS treatment (20 mg/kg/day) or saline solution for 15 days, the animals will be euthanized and the thoracic portion of the aorta will be removed. After processing, the material will be submitted to RNA extraction and to the analysis of gene expression via qPCR. The markers of kidney damage will be evaluated using commercial biochemical kits.