Amaral María M, Girard Magalí C, Álvarez Romina S, Paton Adrienne W, Paton James C, Repetto Horacio A, Sacerdoti Flavia, Ibarra Cristina A
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.
Toxins (Basel). 2017 Jul 18;9(7):226. doi: 10.3390/toxins9070226.
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 (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.
溶血尿毒综合征（HUS）是儿童急性肾衰竭最常见的病因之一。大多数病例与产志贺毒素（Stx）的大肠杆菌（STEC）有关。在阿根廷，HUS呈地方性流行，且发病率为全球最高。表达2型志贺毒素（Stx2）的STEC菌株是导致该病症最严重病例的原因。枯草杆菌蛋白酶细胞毒素（SubAB）是另一种可能导致HUS发病机制的STEC毒力因子。迄今为止，尚无获批用于人类的HUS疫苗或有效疗法。鉴于哇巴因（OUA）可能预防细胞凋亡过程，在本研究中，我们评估了OUA是否能够避免Stx2和SubAB对人肾小球内皮细胞（HGEC）和人近端肾小管上皮细胞系（HK-2）造成的损伤。HGEC和HK-2先用OUA预处理，然后与毒素一起孵育。OUA保护HGEC的活力免受Stx2和SubAB的细胞毒性作用，还防止HK-2的活力受到Stx2的影响。OUA对HGEC和HK-2的保护作用与细胞凋亡减少和细胞增殖增加有关。我们的数据提供了证据，表明OUA可被视为一种治疗策略，以避免HUS之前的肾损伤。
