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

SÁNCHEZ DS; FISCHER SIGEL LK; BALESTRACCI A; IBARRA C; AMARAL MM; SILBERSTEIN C

PEDIATRIC RESEARCH

INT PEDIATRIC RESEARCH FOUNDATION, INC

Lugar: The Woodlands, Texas; Año: 2021

0031-3998

BackgroundShiga 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 of glycosphingolipid biosynthesis, actually used for the treatment of Gaucher?s disease. The aim of the present work was to evaluate the efficiency of EG in preventing the damage caused by Stx2 in human renal epithelial cells.MethodsHuman renal tubular epithelial cell (HRTEC) primary cultures were pre-treated with different dilutions of EG followed by co-incubation with EG and Stx2 at different times, and cell viability, proliferation, apoptosis, tubulogenesis, and Gb3 expression were assessed.ResultsIn HRTEC, pre-treatments with 50 nmol/L EG for 24 h, or 500 nmol/L EG for 6 h, reduced Gb3 expression and totally prevented the effects of Stx2 on cell viability, proliferation, and apoptosis. EG treatment also allowed the development of tubulogenesis in 3D-HRTEC exposed to Stx2.ConclusionsEG could be a potential therapeutic drug for the prevention of acute kidney injury caused by Stx2.