Treatment of experimental chronic chagas disease with trifluralin.

Abstract

We tested trifluralin against Trypanosoma cruzi in a model of chronic Chagas disease in mice. CF1 mice (n=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 (n=48). At day 90 of the chronic disease (74% survival) mice were divided into three groups and treated orally with trifluralin (50 mg/kg/day, n=26), benznidazole (50 mg/kg/day, n=25) and vehicle (peanut oil; control group, n=23) 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, P=0.03). Microstrouts were negative in all three groups. Negative immunofluorescence titers were 0%, 16% (P=0.05) and 29% (P<0.02) 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. Trifluralin- and 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.

• Authors: Anibal Zaidenberg, Tai Luong, Darío Lirussi, Jorge Bleiz, María Beatriz Del Buono, Graciela Quijano, Ricardo Drut, Leonora Kozubsky, Adriana Marron, Héctor Buschiazzo
• Journal: Basic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol) Vol. 98 Issue 4 Pg. 351-6 (Apr 2006) ISSN: 1742-7835 [Print] England
• PMID: 16623857 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Herbicides
• Nitroimidazoles
• Trypanocidal Agents
• Trifluralin
• benzonidazole

Topics

• Animals
• Chagas Disease (drug therapy, parasitology, physiopathology)
• Disease Models, Animal
• Electrocardiography
• Heart (parasitology)
• Herbicides (therapeutic use)
• Male
• Mice
• Mice, Inbred Strains
• Myocarditis (drug therapy, parasitology, physiopathology)
• Nitroimidazoles (therapeutic use)
• Trifluralin (therapeutic use)
• Trypanocidal Agents (therapeutic use)
• Trypanosoma cruzi (drug effects)