Treatment of experimental chronic chagas disease with trifluralin.
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.
Zaidenberg
Anibal
A
Institute of Paediatric Research (IDIP-CIC), Children's Hospital "Sor María Ludovica", Argentina. azaidenberg@hotmail.com
Luong
Tai
T
Lirussi
Darío
D
Bleiz
Jorge
J
Del Buono
María Beatriz
MB
Quijano
Graciela
G
Drut
Ricardo
R
Kozubsky
Leonora
L
Marron
Adriana
A
Buschiazzo
Héctor
H
D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology / Q000503:physiopathology; D004195:Disease Models, Animal; D004562:Electrocardiography; D006321:Heart / Q000469:parasitology; D006540:Herbicides / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009205:Myocarditis / Q000188:drug therapy / Q000469:parasitology / Q000503:physiopathology; D009593:Nitroimidazoles / Q000627:therapeutic use; D014274:Trifluralin / Q000627:therapeutic use*; D014344:Trypanocidal Agents / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000187:drug effects
D006540:Herbicides; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D014274:Trifluralin; C009999:benzonidazole