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Open AccessArticle

Ouabain Protects Human Renal Cells against the Cytotoxic Effects of Shiga Toxin Type 2 and Subtilase Cytotoxin

Laboratorio de Fisiopatogenia, Departamento de Fisiología, Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO Houssay-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires 1121, Argentina
Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, University of Adelaide, Adelaide 5005, Australia
Servicio de Pediatría, Hospital Nacional Profesor Alejandro Posadas, Buenos Aires 1684, Argentina
Author to whom correspondence should be addressed.
Academic Editor: Gerald B. Koudelka
Toxins 2017, 9(7), 226;
Received: 20 June 2017 / Revised: 10 July 2017 / Accepted: 12 July 2017 / Published: 18 July 2017
(This article belongs to the Collection Shiga Toxins)
Hemolytic uremic syndrome (HUS) is one of the most common causes of acute renal failure in children. The majority of cases are associated with Shiga toxin (Stx)-producing Escherichia coli (STEC). In Argentina, HUS is endemic and presents the highest incidence rate in the world. STEC strains expressing Stx type 2 (Stx2) are responsible for the most severe cases of this pathology. Subtilase cytotoxin (SubAB) is another STEC virulence factor that may contribute to HUS pathogenesis. To date, neither a licensed vaccine nor effective therapy for HUS is available for humans. Considering that Ouabain (OUA) may prevent the apoptosis process, in this study we evaluated if OUA is able to avoid the damage caused by Stx2 and SubAB on human glomerular endothelial cells (HGEC) and the human proximal tubule epithelial cell (HK-2) line. HGEC and HK-2 were pretreated with OUA and then incubated with the toxins. OUA protected the HGEC viability from Stx2 and SubAB cytotoxic effects, and also prevented the HK-2 viability from Stx2 effects. The protective action of OUA on HGEC and HK-2 was associated with a decrease in apoptosis and an increase in cell proliferation. Our data provide evidence that OUA could be considered as a therapeutic strategy to avoid the renal damage that precedes HUS. View Full-Text
Keywords: shiga toxin; subtilase cytotoxin; Hemolytic Uremic Syndrome; Ouabain; prevention shiga toxin; subtilase cytotoxin; Hemolytic Uremic Syndrome; Ouabain; prevention
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Amaral, M.M.; Girard, M.C.; Álvarez, R.S.; Paton, A.W.; Paton, J.C.; Repetto, H.A.; Sacerdoti, F.; Ibarra, C.A. Ouabain Protects Human Renal Cells against the Cytotoxic Effects of Shiga Toxin Type 2 and Subtilase Cytotoxin. Toxins 2017, 9, 226.

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