Prevention of renal damage caused by Shiga toxin type 2: Action of Miglustat on human endothelial and epithelial cells

GIRARD MAGALÍ; SACERDOTI FLAVIA; RIVERA FULTON PAUL; REPETTO HORACIO; IBARRA CRISTINA; AMARAL MARIA MARTA

TOXICON

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2015 vol. 105 p. 27 - 33

0041-0101

Typical hemolytic uremic syndrome (HUS) is responsible for acute and chronic renal failure in children younger than 5 years old in Argentina. Renal damages have been associated with Shiga toxin type 1 and/or 2 (Stx1, Stx2) produced by Escherichia coli O157:H7, although strains expressing Stx2 are highly prevalent in Argentina. Human glomerular endothelial cells (HGEC) and proximal tubule epithelial cells are very Stx sensitive since they express high levels of Stx receptor (Gb3). Nowadays, there is no available therapy to protect patients from acute toxin-mediated cellular injury. New strategies have been developed based on the Gb3 biosynthesis inhibition through blocking the enzyme glucosylceramide (GL1) synthase. We assayed the action of a GL1 inhibitor (Miglustat: MG), on the prevention of the renal damage induced by Stx2.HGEC primary cultures and HK-2 cell line were pre-treated with MG and then incubatedwith Stx2. HK-2 and HGEC express Gb3 and MG was able to decrease the levels of this receptor. As a consequence, both types of cells were protected from Stx2 cytotoxicity andmorphology damage. MG was able to avoid Stx2 effects in human renal cells and could be a feasible strategy to protect kidney tissues from the cytotoxic effects of Stx2 in vivo.