Eliglustat, an inhibitor of Gb3 receptor synthesis, protects human microvascular endotelial cells from Shiga toxin type 2 cytotoxicity.

VELEZ DANIEL; AMARAL MARÍA MARTA; BALESTRACCI ALEJANDRO; GOMEZ FERNANDO D; IBARRA CRISTINA

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica.; 2019

Sociedad Argentina de Investigación Clínica

Hemolytic Uremic Syndrome associated to Shiga toxin (Stx)-producing E. coli infection is the most commoncause of acute renal failure (ARF) in children in Argentina. Stx2 binds the globotriaosylceramide(Gb3) receptor and causes direct damages on human renal microvascularendothelial cells (HGEC). In this work, we assayed the action of a Gb3synthesis inhibitor, Eliglustat (EG), to prevent the Stx2 cytotoxicity on humanrenal cells. Cell viability was analyzed by neutral red uptake and data areexpressed as mean ± SEM. Cell morphology analysis was evaluated by lightmicroscopy after staining with H&E. Cell counts were performed on fivefields and cell area values were obtained using Image J software. Necrosis andapoptosis were detected by flow cytometry after Annexin V-FITC/PI doublestaining assay. Non-cytotoxic concentrations of EG were established on HGECtreated with EG (0.05µM-50µM) for 120 h. While EG (50µM) caused a significantdecreased of cell viability (EG (50µM): 8.3 ± 0.9% vsCtrl: 100 ±2.7%, n = 3, p