Fig 3. Effect of benznidazole/itraconazole combination treatment on chronic cardiac lesions.

Mice were inoculated with 5,000 Trypanosoma cruzi Y strain trypomastigotes by the intraperitoneal route and were treated with daily doses 100 mg/kg of bodyweight of benznidazole (Bz) or itraconazole (Itz) alone or in combination at doses of 50, 75 and 100 mg/kg of bodyweight of each drug for 20 consecutive days. Animals were euthanized six months post treatment. Uninfected control (NIC) groups were also evaluated. (a) Myocardial inflammatory cell count in heart muscle of mice, and (b) Fibrotic areas in the heart muscle of treated and uninfected mice. (c-n) Analysis of histological sections of hearts from mice, 40 x magnification: (c-h) Hematoxylin-Eosin staining for inflammation assessment and (i-n) Masson’s trichrome stain for fibrosis assessment. (c and i) Myocardial sections from healthy mice; (d and j) from infected benznidazole 100 mg/kg-treated; (e and k) from infected itraconazole 100 mg/kg-treated; (f and l) from benznidazole (100 mg/kg)/itraconazole (100 mg/kg)-treated; (g and m) from benznidazole (75 mg/kg)/itraconazole (75 mg/kg)-treated; (h and n) benznidazole (50 mg/kg)/itraconazole (50 mg/kg)-treated. & significant difference in relation to uninfected control. ★+Significant difference in relation to itraconazole (★) and benznidazole (+) treatments administered at the optimal dose (100 mg/kg).