Benznidazole prevents endothelial damage in an experimental model of Chagas disease

• We administered 30 or 100 mg/kg/day benznidazole to Chagasic mice early in the infection.
• Parasitaemia, mortality, cardiac and endothelial dysfunction markers were measured.
• 30 mg/kg Benznidazole prevents cardiac damage and modulates endothelial activation.

ObjectivesTo evaluate the effect of benznidazole on endothelial activation in a murine model of Chagas disease.MethodsA low (30 mg/kg/day) and a high (100 mg/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.ResultsBenznidazole 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.ConclusionsEarly administration of benznidazole at a dose as low as 30 mg/kg eradicates T. cruzi from cardiac tissue. Additionally, benznidazole prevents cardiac damage and modulates endothelial activation as part of its antichagasic activity.

30 or 100 mg/kg/day benznidazole were administered to chagasic mice early in the infection. Parasitaemia, mortality, cardiac and endothelial dysfunction markers were measured. 30 mg/kg Benznidazole prevents cardiac damage and modulates endothelial activation.Figure optionsDownload as PowerPoint slide