Abstract
Context: Though typical Hemolytic Uremic Syndrome - mainly caused by Shiga toxin (Stx) produced by Escherichia coli - is a major cause of acute renal failure in children, the available treatments remain symptomatic. The aim of our experimental study was to determine whether ouabain (OB) at non-inhibitive concentrations could decrease the shigatoxin-induced apoptotic level.
Methods: Experiments were performed in rat proximal tubule cells (RPTC) cultured with Stx 2-4ng/mL, and treated with OB 5-10 nM. Group comparison was measured with the Apoptotic index, DNA fragmentation, and Fluorescence activated cell sorter (FACS). Immunoprecipitation and immunostaining techniques were used to determine the pathway of the antiapototic effect of OB.
Results: Stx 3-4 ng/mL significantly increased the apoptotic index in comparison to the control group. OB 5 nM significantly decreased the apoptotic index in RPTC exposed to Stx 3- 4 ng/mL (Apotptotic index %: Stx3 6.4±3.2 versus Stx3+OB 1.5±2.4, p=0.003; Stx4 8.6±8.9 vs. 2.1±1.3, p< 10-4). It also decreased the level of DNA. FACS analyses demonstrated that OB drastically protected RPTC from Stx cytotoxins. Furthermore, immunoprecipitation as well as specific immunostaining showed that OB's protective effect was mediated through the Na, K-ATPase /IP3R interaction and triggering NFkB activity.
Conclusion: Our results state that ouabain may be an interesting therapeutic agent to reduce kidney damage in children with HUS.
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Vieux, R., Burlaka, E., Yang, L. et al. 354 Ouabain Protects Against Shiga Toxin Induced Renal Tubular Cell Apoptosis. Pediatr Res 68 (Suppl 1), 183 (2010). https://doi.org/10.1203/00006450-201011001-00354
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DOI: https://doi.org/10.1203/00006450-201011001-00354