Abstract
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.
Highlights
The Hemolytic Uremic Syndrome (HUS) was described in 1973 by Gianantonio et al as systemic complications characterized by non-immune hemolytic anemia, thrombocytopenia, and acute renal failure (ARF) [1]
Concentrations of OUA above 30 nM were cytotoxic for both human glomerular endothelial cells (HGEC) and HK-2 was not affected
OUA increased the percentage of HGEC in the S phase with respect to Ctrl, and it was able to prevent the effects of Stx type 2 (Stx2), as shown for the G2M phase in OUA +
Summary
The Hemolytic Uremic Syndrome (HUS) was described in 1973 by Gianantonio et al as systemic complications characterized by non-immune hemolytic anemia, thrombocytopenia, and acute renal failure (ARF) [1]. Infection called diarrhea-associated HUS [2]. In Argentina, diarrhea-associated HUS is endemic and the incidence rate is the highest in the world, for reasons that are still unknown. In the last 10 years, about 400 cases per year have been registered, with an incidence of 10 to 17 cases per 100,000 children under five years of age, and with a case fatality rate from 1 to 4% [3]. HUS is the most common cause of ARF in children, the second leading cause of chronic renal failure in children younger than five years old, and is responsible for 20% of kidney transplants in children and adolescents [4].
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