A cardiovascular dynamic analysis in zebrafish embryos reveals trifloxystrobin-induced cardiovascular dysfunction.

In this study, we investigated the toxicological mechanisms of trifloxystrobin (TFX), a widely used strobilurin fungicide, on zebrafish embryos, focusing on cardiovascular development and function. Embryos were exposed to TFX (100-500 μg/L) for 96 h. The compound exhibited high acute toxicity with a 96-h median lethal concentration (LC50) of ~320 μg/L. At 200-300 μg/L, TFX induced bioenergetic impairment, manifested as growth retardation and nutrient retention in the yolk sac. The prevalence of pericardial edema served as a hallmark of cardiac dysfunction, prompting a detailed functional assessment. A detailed cardiovascular analysis revealed a critical hemodynamic paradox. While TFX-exposed embryos exhibited bradycardia and a compensatory increase in the ventricular ejection fraction and wall thickness, effective systemic circulation was severely compromised. An advanced regurgitation analysis demonstrated that TFX caused severe atrioventricular valve insufficiency and retrograde blood flow, leading to a significant overestimation of cardiac output when calculated by standard volumetric methods alone. An analysis of the dorsal aorta confirmed a genuine reduction in the arterial blood flow velocity, validating the presence of circulatory failure despite myocardial hyper-contractility. Mechanistically, the hemodynamic alteration was linked to significant downregulation of the klf2a flow-sensitive transcription factor, which impaired valve morphogenesis, while the concurrent upregulation of nppa, nppb, and gata4 signaled pathological cardiac stress and hypertrophy. These findings elucidate a mechano-molecular toxicity pathway for TFX and highlight the technical necessity of coupling a regurgitation analysis with peripheral flow assessment to accurately evaluate cardiac toxicity in aquatic models.