title: Benznidazole prevents endothelial damage in an experimental model of Chagas disease.
abstract: OBJECTIVE
  To evaluate the effect of benznidazole on endothelial activation in a murine model of Chagas disease.
  
  
  METHODS
  A low (30mg/kg/day) and a high (100mg/kg/day) dose of benznidazole were administered to mice infected with Trypanosoma cruzi during the early phases of the infection. The effects of the treatments were assessed at 24 and 90 days postinfection by evaluating the parasitaemia, mortality, histopathological changes and expression of ICAM in the cardiac tissue. The blood levels of thromboxane A2, soluble ICAM and E-selectin were also measured. T. cruzi clearance was assessed by the detection of parasite DNA in the heart tissue of infected mice.
  
  
  RESULTS
  Benznidazole decreased the cardiac damage induced by the parasite, and amastigote nests disappeared at 90 days postinfection. Both doses cleared the parasite from the cardiac tissue at 24 and 90 days postinfection. In addition, benznidazole decreased the thromboxane levels and normalized the plasma sICAM and sE-selectin levels by 90 days postinfection.
  
  
  CONCLUSIONS
  Early administration of benznidazole at a dose as low as 30mg/kg eradicates T. cruzi from cardiac tissue. Additionally, benznidazole prevents cardiac damage and modulates endothelial activation as part of its antichagasic activity.
authors.affiliation: Centro de Investigación Biomédica, Facultad de Medicina, Universidad Diego Portales, Av. Ejercito 141, Santiago, Chile.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Molina-Berríos
authors.forename: Carolina
authors.initials: C
authors.lastname: Campos-Estrada
authors.forename: Michel
authors.initials: M
authors.lastname: Lapier
authors.forename: Juan
authors.initials: J
authors.lastname: Duaso
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kemmerling
authors.forename: Norbel
authors.initials: N
authors.lastname: Galanti
authors.forename: Mario
authors.initials: M
authors.lastname: Leiva
authors.forename: Jorge
authors.initials: J
authors.lastname: Ferreira
authors.forename: Rodrigo
authors.initials: R
authors.lastname: López-Muñoz
authors.forename: Juan Diego
authors.initials: JD
authors.lastname: Maya
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009593:Nitroimidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014349:Trypanosoma cruzi
chemical_list: D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C009999:benzonidazole