Abstract:We tested trifluralin against Trypanosoma cruzi in a model of chronic Chagas disease in mice. CF1 mice (nΩ 148) were intraperitoneally infected with 10 5 trypomastigotes of T. cruzi, H510C8C3 clone. One hundred mice were partially treated with benznidazole. Mortality was 100% at day 41 in the control group (nΩ48). At day 90 of the chronic disease (74% survival) mice were divided into three groups and treated orally with trifluralin (50 mg/kg/day, nΩ26), benznidazole (50 mg/kg/day, nΩ25) and vehicle (peanut oil; control group, nΩ23) for 60 days. Electrocardiography (under pentobarbital anaesthesia, 30 mg/kg/dose), serologic immunofluorescence and microstrout were performed at the beginning and at the end of the treatment. Mice were sacrificed at day 10 after treatment; cardiac tissue was studied histopathologically and polymerase chain reaction (PCR) was performed. Spontaneous mortality was 30.43%, 3.85% and 4% in the control, trifluralin and benznidazole groups, respectively (significant survival, PΩ0.03). Microstrouts were negative in all three groups. Negative immunofluorescence titers were 0%, 16% (PΩ0.05) and 29% (PϽ0.02) in the control, trifluralin and benznidazole groups, respectively. The prevailing electrocardiographic disorder was prolongation of the PR interval in the control group, which was not significantly altered in trifluralin-and benznidazole-treated mice, suggesting that trifluralin and benznidazole improve or even stop the damage caused by the disease on the conduction system. Trifluralinand benznidazole-treated animals showed similar histologic patterns of myocarditis. PCR results were negative for benznidazole and trifluralin (100% and 70.8%, respectively). These results show the therapeutic potential of trifluralin in the treatment of chronic Chagas disease.
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