A cardiovascular dynamic analysis in zebrafish embryos reveals trifloxystrobin-induced cardiovascular dysfunction
Jiun-Lin Horng1, Yueh-Tzu Kao2, Li-Yih Lin3
1Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
Summary
Trifloxystrobin (TFX) fungicide causes zebrafish embryo heart defects, including valve issues and circulatory failure, despite increased heart contraction. Accurate cardiac toxicity assessment requires advanced regurgitation and flow analysis.
Area of Science:
- Environmental Toxicology
- Cardiovascular Physiology
- Developmental Biology
Background:
- Strobilurin fungicides, like trifloxystrobin (TFX), are widely used in agriculture.
- Understanding the toxicological mechanisms of TFX on non-target organisms is crucial for environmental risk assessment.
- Zebrafish embryos are a valuable model for studying developmental toxicity due to their optical transparency and rapid development.
Purpose of the Study:
- To investigate the toxicological mechanisms of trifloxystrobin (TFX) on zebrafish embryo cardiovascular development and function.
- To elucidate the specific cardiac defects induced by TFX exposure.
- To identify the molecular pathways involved in TFX-induced cardiotoxicity.
Main Methods:
- Zebrafish embryos were exposed to various concentrations of TFX (100-500 μg/L) for 96 hours.
- Acute toxicity was assessed by determining the median lethal concentration (LC50).
- Cardiovascular function was evaluated using detailed analysis of heart rate, ejection fraction, wall thickness, valve function, and blood flow velocity in the dorsal aorta. Molecular analysis included gene expression profiling (klf2a, nppa, nppb, gata4).
Main Results:
- TFX exhibited high acute toxicity (96-h LC50 ~320 μg/L) and caused bioenergetic impairment at lower doses.
- Cardiac dysfunction was characterized by bradycardia, increased ventricular contractility, and severe atrioventricular valve insufficiency leading to retrograde blood flow.
- TFX exposure resulted in reduced arterial blood flow velocity, downregulation of klf2a, and upregulation of nppa, nppb, and gata4, indicating impaired valve morphogenesis and pathological cardiac stress.
Conclusions:
- Trifloxystrobin induces significant cardiovascular toxicity in zebrafish embryos through a mechano-molecular pathway involving impaired valve development and function.
- Accurate assessment of cardiac toxicity requires advanced methods, including regurgitation analysis and peripheral flow assessment, beyond standard volumetric calculations.
- These findings highlight the potential risks of TFX to aquatic ecosystems and underscore the need for comprehensive toxicological evaluations.
