Trifluralin toxicity in a Chagas disease mouse model

Area of Science:

• Toxicology
• Pharmacology
• Parasitic Diseases

Background:

• Trifluralin demonstrates efficacy in treating experimental Chagas disease.
• Further preclinical toxicity assessments are essential to evaluate its safety profile.

Purpose of the Study:

• To investigate the cellular toxicity of trifluralin in Hep-G2 and Vero C76 cell lines.
• To assess the acute and chronic toxicity of trifluralin in CF1 mice, examining various physiological and histological parameters.

Main Methods:

• Cell viability assays were performed on Hep-G2 and Vero C76 cells exposed to trifluralin (50 and 150 microM).
• CF1 mice received oral trifluralin daily for 30 days (acute) or weekly for 90 days (chronic).
• Hematological, biochemical, and histological analyses were conducted, with a focus on hepatic, pancreatic, and cardiac functions.

Main Results:

• Cellular studies showed no significant toxicity in Hep-G2 and Vero C76 cells.
• Mice treated with trifluralin exhibited decreased red blood cell indices (mean corpuscular volume, hemoglobin, hematocrit).
• Elevated cardiac enzyme levels (creatine phosphokinase, lactate dehydrogenase, glutamic-oxalacetic transaminase) and mild myocarditis were observed in treated mice.

Conclusions:

• Trifluralin appears to be a moderately toxic agent with a potential selective cardiotoxic effect.
• Despite observed cardiac effects, trifluralin's therapeutic potential for Chagas disease warrants further investigation within a risk-benefit framework.