Eliglustat prevents Shiga toxin 2 cytotoxic effects in human renal tubular epithelial cells

FISHER SIGEL LILIANA KARINA; AMARAL MARIA MARTA; BALESTRACCI ALEJANDRO; SILBERSTEIN CLAUDIA; SANCHEZ DIANA; IBARRA CRISTINA

PEDIATRIC RESEARCH

INT PEDIATRIC RESEARCH FOUNDATION, INC

Lugar: The Woodlands, Texas; Año: 2021

0031-3998

BACKGROUND: Shiga toxin-producing Escherichia coli is responsible for post-diarrheal (D+) hemolytic uremic syndrome (HUS),which is a cause of acute renal failure in children. The glycolipid globotriaosylceramide (Gb3) is the main receptor for Shiga toxin(Stx) in kidney target cells. Eliglustat (EG) is a specific and potent inhibitor of glucosylceramide synthase, first step ofglycosphingolipid biosynthesis, actually used for the treatment of Gaucher?s disease. The aim of the present work was to evaluatethe efficiency of EG in preventing the damage caused by Stx2 in human renal epithelial cells.METHODS: Human renal tubular epithelial cell (HRTEC) primary cultures were pre-treated with different dilutions of EG followed byco-incubation with EG and Stx2 at different times, and cell viability, proliferation, apoptosis, tubulogenesis, and Gb3 expressionwere assessed.RESULTS: In HRTEC, pre-treatments with 50 nmol/L EG for 24 h, or 500 nmol/L EG for 6 h, reduced Gb3 expression and totallyprevented the effects of Stx2 on cell viability, proliferation, and apoptosis. EG treatment also allowed the development oftubulogenesis in 3D-HRTEC exposed to Stx2.CONCLUSIONS: EG could be a potential therapeutic drug for the prevention of acute kidney injury caused by Stx2.