{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T19:48:18Z","timestamp":1782935298453,"version":"3.54.5"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008441","name":"CYTED Ciencia y Tecnolog\u00eda para el Desarrollo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008441","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Shiga toxin-producing\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      is the main cause of post-diarrheal hemolytic uremic syndrome (HUS), which produces acute kidney injury mainly in children. Shiga toxin exerts its action by binding to the glycolipid globotriaosylceramide (Gb3) on the cell surface of target tissues. In humans, the kidneys are the organs most affected by Shiga toxin, where high Gb3 expression in glomerular endothelial and tubular epithelial cells leads to a combined glomerulopathy and tubulopathy that drives acute kidney injury. The aim of the present work was to evaluate the effectiveness of oral treatment with eliglustat (EG), an inhibitor of glucosylceramide synthase, the first step of glycosphingolipid biosynthesis, in preventing the effects of Shiga toxin 2 (Stx2) in lethal and sublethal models of HUS in rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male juvenile Sprague\u2013Dawley rats (\u223c100\u00a0g body weight (bw)) were intraperitoneally injected with lethal (5\u00a0ng\/g bw) or sublethal (1\u00a0ng\/g bw) doses of Stx2, or eluent. Some rats were orally treated with EG (15\u00a0mg\/d or 25\u00a0mg\/d) for 0\u20132 days, until 2\u00a0days or 3 days post-injection. Rat survival, renal Gb3 expression, renal function, histopathological observations, and aquaporin 1 (AQP1) and neutrophil gelatinase-associated lipocalin (NGAL) tubular expression were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Rats injected with the Stx2 lethal dose showed significant kidney injury with extended tubular necrosis and some glomerular alterations at 3\u00a0days post-injection. The Stx2 sublethal dose caused significantly less renal injury extension than the lethal dose, showing only tubular damage. The expression of AQP1 and NGAL corroborated the tubular alteration in Stx2-injected rats. The oral treatment with EG reduced Gb3 renal levels and, therefore, significantly prevented the renal injury caused by lethal and sublethal doses of Stx2 in rats. Moreover, the pretreatment for 2\u00a0days with EG prevented the mortality in those rats injected with the Stx2 lethal dose. The EG treatment did not cause renal or systemic alterations. The effectiveness of EG treatment depended on the dose and the pretreatment time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The oral treatment with EG could be a therapeutic strategy to prevent the action of Stx2 and the development of acute kidney injury in diarrhea-associated HUS patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1736204","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T06:40:44Z","timestamp":1771483244000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Eliglustat prevents acute kidney injury caused by Shiga toxin 2 in lethal and sublethal rat models of hemolytic uremic syndrome"],"prefix":"10.3389","volume":"17","author":[{"given":"Daiana S.","family":"S\u00e1nchez","sequence":"first","affiliation":[{"name":"Universidad de Buenos Aires (UBA), Facultad de Ciencias M\u00e9dicas, Departamento de Ciencias Fisiol\u00f3gicas, Laboratorio de Fisiolog\u00eda Renal","place":["Buenos Aires, Argentina"]},{"name":"Universidad de Buenos Aires \u2013 Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas (CONICET), Instituto de Fisiolog\u00eda y Biof\u00edsica Bernardo Houssay (IFIBIO Houssay)","place":["Buenos Aires, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian K.","family":"Fischer Sigel","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires (UBA), Facultad de Ciencias M\u00e9dicas, Departamento de Ciencias Fisiol\u00f3gicas, Laboratorio de Fisiolog\u00eda Renal","place":["Buenos Aires, Argentina"]},{"name":"Universidad de Buenos Aires \u2013 Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas (CONICET), Instituto de Fisiolog\u00eda y Biof\u00edsica Bernardo Houssay (IFIBIO Houssay)","place":["Buenos Aires, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa","family":"Zotta","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, Departamento de Ciencias Biol\u00f3gicas, C\u00e1tedra de Fisiopatolog\u00eda","place":["Buenos Aires, Argentina"]},{"name":"Universidad de Buenos Aires, Facultad de Ciencias M\u00e9dicas, Departamento de Ciencias Fisiol\u00f3gicas. 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