Enantioselective acute toxicity, oxidative stress effects, neurotoxicity, and thyroid disruption of uniconazole in zebrafish (Danio rerio)

Uniconazole is a widely used plant growth retardant in the agricultural field. However, toxicological effects of uniconazole in aquatic ecosystem at chiral level are still unclear. Herein, acute toxicity, oxidative stress effects, neurotoxicity, and thyroid disruption of uniconazole enantiomers were investigated through using zebrafish as a model. (R)-Uniconazole possessed 1.16-fold greater acute toxicity to zebrafish than (S)-enantiomer. Then, integrated biomarker response values of oxidative stress parameters in zebrafish exposed to (R)-uniconazole were about 1.27~1.53 times greater than those treated by (S)-uniconazole, revealing that (R)-uniconazole could result in more significant adverse effects than (S)-uniconazole. Subsequently, the results of acetylcholinesterase activity of experimental fish demonstrated a state of inhibition-activation-inhibition after 14-day exposure to uniconazole, and a significant enantioselective neurotoxicity of uniconazole was observed in zebrafish after exposure for 4 and 7 days (p < 0.05). Moreover, thyroxine and triiodothyronine contents in (R)-uniconazole-exposed zebrafish were 0.89-fold (p=0.007) and 0.80-fold (p=0.007) than those in (S)-enantiomer-treated group, respectively. Furthermore, molecular docking results between uniconazole enantiomers and thyroid hormone receptors revealed that (R)-uniconazole was more tightly bound than (S)-uniconazole to the receptors. Briefly, our findings provide favorable information for ecological risk assessments of chiral agrochemicals in the environment and health of aquatic organisms.Graphical abstract