Evaluation of cardiac toxicity of a neonicotinoid insecticide, dinotefuran, in a zebrafish heart failure animal model.

Dinotefuran, a widely used neonicotinoid insecticide, is environmentally persistent and frequently detected in aquatic systems, raising concerns for non-target organisms. However, its cardiotoxic effects remain unclear. Here, we provide the first comprehensive evidence of its cardiotoxicity in normal and heart failure zebrafish model. Dinotefuran exposure increased the incidence of uninflated swim bladders, reduced survival and locomotor activity in a dose-dependent manner. Cardiac structure was altered, with looping defects more frequent, as the incidence of no-loop formations increased from 13 % to 37 %, and the atrium-ventricle ratio rose from 0.9 to 1.4. Cardiac function was impaired, with contractile performance declining as ejection fraction decreased from 43 % to 29 % and relative cardiac output from 0.3 to 0.1. Rhythm stability was also reduced, with reduced heart rate and increased beat-to-beat variability by 43 %. At the cellular level, dinotefuran markedly promoted apoptosis and upregulated reactive-oxygen species (ROS)-related genes without antioxidant compensation. In parallel, the cardiac stress marker was induced by two-folds, and maladaptive shifts in chamber-specific gene. In conclusion, dinotefuran exerted impaired cardiotoxicity through oxidative stress, highlighting its environmental and human health risks. Future studies should validate these mechanisms in mammalian and human-relevant systems and assess the effects of chronic exposures to better define long-term health and environmental risks.