Mitochondrial dysfunction-based cardiotoxicity and neurotoxicity induced by pyraclostrobin in zebrafish larvae

Pyraclostrobin is widely used to control crop diseases, and was reported to be highly toxic to aquatic organisms. The molecular target of pyraclostrobin to fungus is the mitochondrion, but its effect on mitochondria of aquatic organisms has rarely been investigated. In this study, zebrafish larvae at 4 days post fertilization (dpf) were exposed to a range of pyraclostrobin for 96 h to assess its acute toxicity and effects on mitochondria. Pyraclostrobin at 36 μg/L or higher concentrations caused significant influences on larval heart and brain including pericardial edema, brain damage malformations, histological and mitochondrial structural damage of the two organs. The results of RNA-Seq revealed that the transcripts of genes related to oxidative phosphorylation, cardiac muscle contraction, mitochondrion, nervous system development and glutamate receptor activity were significantly influenced by 36 μg/L pyraclostrobin. Further tests showed that pyraclostrobin at 18 and 36 μg/L reduced the concentrations of proteins related to cardiac muscle contraction, impaired cardiac function, inhibited glutamate receptors activities and suppressed locomotor behavior of zebrafish larvae. Negative changes in mitochondrial complex activities, as well as reduced ATP content were also observed in larvae treated with 18 and 36 μg/L pyraclostrobin. These results suggested that pyraclostrobin exposure caused cardiotoxicity and neurotoxicity in zebrafish larvae and mitochondrial dysfunction might be the underlying mechanism of pyraclostrobin toxicity.

Cardiotoxicity; Mitochondrial dysfunction; Neurotoxicity; Pyraclostrobin; Zebrafish larvae.