OBJECTIVES: 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.
OBJECTIVES: 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.
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Authors: Leonel A Cortes; Lorena Castro; Bárbara Pesce; Juan D Maya; Jorge Ferreira; Vicente Castro-Castillo; Eduardo Parra; José A Jara; Rodrigo López-Muñoz Journal: PLoS One Date: 2015-08-28 Impact factor: 3.240
Authors: Paloma Marina de la Torre-Iglesias; Juan José García-Rodriguez; Guillermo Torrado; Susana Torrado; Santiago Torrado-Santiago; Francisco Bolás-Fernández Journal: Drug Des Devel Ther Date: 2014-09-18 Impact factor: 4.162
Authors: Zumira A Carneiro; Pedro I da S Maia; Renata Sesti-Costa; Carla D Lopes; Tatiana A Pereira; Cristiane M Milanezi; Marcelo A Pereira da Silva; Renata F V Lopez; João S Silva; Victor M Deflon Journal: PLoS Negl Trop Dis Date: 2014-05-08
Authors: Amanda Fortes Francisco; Shiromani Jayawardhana; Michael D Lewis; Karen L White; David M Shackleford; Gong Chen; Jessica Saunders; Maria Osuna-Cabello; Kevin D Read; Susan A Charman; Eric Chatelain; John M Kelly Journal: Sci Rep Date: 2016-10-17 Impact factor: 4.379