Trifluralin toxicity in a Chagas disease mouse model.
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.
Zaidenberg
Aníbal
A
Institute of Pediatric Research and Development (La Plata Children's Hospital - Scientific Research Commission of the Province of Buenos Aires CICPBA), La Plata, Argentina. azaidenberg@hotmail.com
Marra
Carlos
C
Luong
Tai
T
Gómez
Pedro
P
Milani
Laura
L
Villagra
Sergio
S
Drut
Ricardo
R
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D014355:Chagas Disease / Q000188:drug therapy*; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D014274:Trifluralin / Q000633:toxicity*; D050257:Tubulin Modulators / Q000633:toxicity*; D014709:Vero Cells
D050257:Tubulin Modulators; D014274:Trifluralin