Toxicity of trifluralin for the treatment of Chagas disease in a mice model .

ANÍBAL ZAIDEMBERG; CARLOS ALBERTO MARRA; TAI LUONG; PEDRO GÓMEZ; LAURA MILANI; SERGIO VILLAGRA; RICARDO DRUT

Basic and Clinical Pharmacology and Toxicology

Blackwell Publishing

Lugar: Copenhagen, Dennmark; Año: 2006

1742-7835

Trifluralin (a,a,a-2,6-dinitro-N-N-dipropyl-p-toluidine, TFL) is effective for the treatment of experimental Chagas disease. However, preclinical toxicity studies should be performed. Cell toxicity was studied in HEP G2 and Vero C76 cells treated with 50 and 100 mM TFL. Results showed that duplication times, amounts of cellular protein and cell protein/DNA values were normal. Histological, hematological and chemical parameters were measured in CF1 mice after oral administration of TFL. Acute or chronic toxicology effects were assayed (n = 20) by administration of 50 or 200 mg/kg/day daily for 30 days, or 200 mg/kg/day once a day for 90 days, respectively. In the acute scheme treatment, hepatic (GOT, GPT, ALP, proteins, albumin) and pancreatic (amylase, glycemia) function were normal. MCV, hemoglobin and hematocrite decreased. CK, LDH and GOT increased, suggesting lesion in myocardiac tissue. Histology was normal, excepting for heart (mild myocarditis). Similar results were observed for the acute-treated animals. There were no differences in body weight gain for treated mice compared with the control ones. In view of the published TFL therapeutic effects on CF1 Chagas disease model, and considering the present results, trifluralin would be a moderately toxic drug with a potential selective effect on myocardium.