title: Development of a Mouse Model of Shiga Toxin 2 (Stx2) Intoxication for Testing Therapeutic Agents Against Hemolytic Uremic Syndrome (HUS).
abstract: Hemolytic Uremic Syndrome (HUS) caused by infections with Shiga toxin (Stx)-producing E. coli is a life-threatening complication characterized by acute renal failure, thrombocytopenia and hemolytic anemia. Stx is the main pathogenic factor. Therefore, the mouse model by intravenous administration of a single lethal dose of Stx is often used to explore its pathogenic mechanisms.
  
  
  
  The aim of this work was to develop an alternative mouse model of Stx type 2 (Stx2) intoxication to evaluate new therapeutic strategies.
  
  
  
  One lethal dose of Stx2 was divided in four daily doses. We observed a dose-dependent toxicity characterized by neutrophilia, leukocytopenia and renal damage. Most importantly, we demonstrated that the polyclonal anti-Stx2 serum was able to protect mice from fatal evolution even when administered together the third dose of Stx2.
  
  
  
  This model would provide an advantage for evaluation of therapeutic strategies. Furthermore, the results presented herein suggest that appropriate treatment with anti-Stx2 agents following the appearance of initial clinical signs may block the ongoing outcome or may alleviate disease in patients who have just been diagnosed with HUS. However, the delay in the onset of therapy would be unsafe.
authors.forename: Maria Pilar
authors.initials: MP
authors.lastname: Mejias
authors.forename: Romina Jimena
authors.initials: RJ
authors.lastname: Fernandez-Brando
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Ramos
authors.forename: Maria Jimena
authors.initials: MJ
authors.lastname: Abrey-Recalde
authors.forename: Elsa
authors.initials: E
authors.lastname: Zotta
authors.forename: Roberto
authors.initials: R
authors.lastname: Meiss
authors.affiliation: Instituto de Medicina Experimental (IMEX) (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081 (C1425AUM), Buenos Aires, Argentina. marinaspalermo@hotmail.com.
authors.forename: Marina Sandra
authors.initials: MS
authors.lastname: Palermo
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006463:Hemolytic-Uremic Syndrome / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D007275:Injections, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000633:toxicity; D022641:Shiga Toxin 2 / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*
chemical_list: D011994:Recombinant Proteins; D022641:Shiga Toxin 2