Chronic exposure to pyraclostrobin induced hepatic toxicity and glucolipid metabolism dysfunction in adult zebrafish

The ecological risks of pyraclostrobin (PY) in the environment have become an increasing concern, yet its chronic toxicity and mechanism to aquatic organisms remain unclear. This study employed histopathological, metabolomic, and transcriptomic analyses to investigate the chronic effects of environmental concentrations of PY and underlying potential toxic mechanism in adult zebrafish. The result showed that 0.24 and 2.4 μg/L PY induced liver damage in zebrafish after 21 d exposure, with 0.24 μg/L PY elicited more pronounced transcriptional and metabolic alterations across diverse pathways in zebrafish liver. Mechanistic analyses showed that PY exposure could decrease the transcription of genes involved in pyrimidine and purine metabolism, thereby disrupting nucleotide synthesis, while simultaneously down-regulating the expression of multiple genes related to DNA replication processes and DNA repair system. Furthermore, PY perturbed hepatic glucolipid metabolism, evidenced by glycerophospholipid accumulation and decreased levels of glucose, pyruvate, triglyceride, cholesterol, and carbohydrates. The reduction in carbohydrates involved in ABC transporters, as well as the disruption in Abcb5, Abcc1, Abcd2, Abcd3 or Abcc10 transcription, suggested that ABC transporters might mediate PY-induced metabolic dysfunction. These findings provided mechanistic insights into PY-induced hepatotoxic effects in zebrafish, highlighting the need to address the chronic toxicity and ecological risks of environmental concentrations of PY for aquatic organisms.