Even though
trifluralin (alpha,alpha,alpha-2,6-dinitro-N-N-dipropyl-p-toluidine) is effective for the treatment of experimental
Chagas disease, more preclinical toxicity studies need to be performed. Cell toxicity of
trifluralin was studied in Hep-G2 and Vero
C76 cells treated with 50 and 150 microM
trifluralin. The results show that duplication time, amount of cellular
protein and cell
protein/
DNA values were normal. Histological, haematological and chemical parameters were measured in CF1 mice after oral
trifluralin administration. Acute toxic effects were assayed by administration of 50 or 200 mg/kg
body weight daily for 30 days, and chronic effects by administration of 200 mg/kg
body weight once a week for 90 days (n = 20). In the acute scheme treatment, hepatic (glutamic-pyruvic, glutamic-oxalacetic and
alkaline phosphatase activities;
proteins and
albumin plasma concentrations) and pancreatic (
amylase, glycaemia) functions were normal. Mean corpuscular volume, haemoglobin and haematocrit decreased.
Creatine phosphokinase,
lactate dehydrogenase and glutamic-oxalacetic activity increased, suggesting lesion in myocardial tissue. Histology was normal, excepting for the heart (mild
myocarditis). Similar results were observed in acutely treated animals. There were no differences in
body weight gain for treated mice compared to controls. In view of the published
therapeutic effects of
trifluralin on CF1
Chagas disease model and considering the present results,
trifluralin seems to be a moderately toxic
drug with a potential selective effect on the myocardium.