info:eu-repo/semantics/article
Prevention of renal damage caused by Shiga toxin type 2: Action of Miglustat on human endothelial and epithelial cells
Fecha
2015-10Registro en:
Girard, Magalí Celeste; Sacerdoti, Flavia; Rivera Albinagorta, Fulton Paul; Repetto, Horacio Antonio; Ibarra, Cristina Adriana; et al.; Prevention of renal damage caused by Shiga toxin type 2: Action of Miglustat on human endothelial and epithelial cells; Pergamon-Elsevier Science Ltd; Toxicon; 105; 10-2015; 27-33
0041-0101
CONICET Digital
CONICET
Autor
Girard, Magalí Celeste
Sacerdoti, Flavia
Rivera Albinagorta, Fulton Paul
Repetto, Horacio Antonio
Ibarra, Cristina Adriana
Amaral, María Marta
Resumen
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 incubated with 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 and morphology 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.