Concentration-dependent multi-biomarker and miR-153 responses to pyridaben toxicity in zebrafish: An IBR-based...

This study investigates the concentration-dependent toxicity (0.206-0.824 µg/L) of pyridaben (PDB) for 48 h in zebrafish (Danio rerio) through an integration of biochemical, molecular, and in silico approaches. Results demonstrate a synchronized antioxidant system, where SOD-GST and CAT-GPX activities exhibit strong positive correlations in both the liver and gills. Molecular docking simulations structurally confirmed that PDB acts as a competitive inhibitor by blocking the CAT active site, while its interaction with the GST enzyme supports a targeted biotransformation response. A key finding was the functional decoupling between molecular and biochemical levels, characterized by an oxidative stress thresholding strategy. Despite near total and continuous repression of sod2 and gclc transcripts, SOD activity showed compensatory increases at higher concentrations, suggesting a reliance on pre-existing enzyme pools once transcriptional support is exhausted. Tissue-specific dynamics were evident in lipid peroxidation; hepatic TBARS levels unexpectedly decreased, while gill TBARS showed a GST-dependent profile, inversely correlating with available detoxification capacity. Gene expression analysis revealed that nrf2 transcripts reached a 20-fold induction at 0.670 µg/L, while miR-153 and hsp70 showed non-linear peaks at intermediate and lower concentrations, respectively. In muscle tissue, PDB induced Ca²⁺-ATPase activity and significantly inhibited AChE at 0.515 µg/L. IBR analysis confirms that environmentally relevant concentrations of PDB severely compromise homeostatic capacity, demonstrating long-term toxic potential for both invertebrate and vertebrate non-target species, consistent with our previous findings in Daphnia magna. Collectively, these multi-level responses reveal that even sublethal PDB exposure poses concentration-dependent oxidative and proteotoxic disruption with significant ecological implications.