Mitochondrial dysfunction, apoptosis and transcriptomic alterations induced by four strobilurins in zebrafish (Danio rerio) early life stages

Abstract

Though the toxicity of strobilurins on non-target aquatic organisms has been characterized, the associated toxic mechanisms have not been fully explored. The present study showed that the larval stage was the most sensitive developmental stage in zebrafish, and pyraclostrobin (PY) had the highest acute toxicity to embryos, larvae, juvenile and adult with 96 h-LC₅₀ at 0.048 mg/L, 0.029 mg/L, 0.039 mg/L, 0.031 mg/L respectively, when compared with the toxicity of trifloxystrobin (TR), kresoxim-methyl (KM) and azoxystrobin (AZ) at corresponding developmental stage. Then we investigated the transcriptomics and developmental toxicity of TR, KM, AZ and PY on zebrafish embryos after 72 h exposure. RNA-seq revealed that the pathways related to cell apoptosis and cancer, and cellular components organelle membrane and mitochondrion, were markedly affected after TR, KM, AZ and PY exposure during zebrafish early life stages. The results were further confirmed by the induction of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) activities, the elevation of H₂O₂, malondialdehyde (MDA) and reactive oxygen species (ROS) level, as well as the reduction of intracellular calcium ions (Ca²⁺) and mitochondrial membrane potential (MMP), which indicated that strobilurins could cause mitochondrial dysfunction and cell apoptosis. The present study was performed a systematic analysis of strobilurins to zebrafish at multi-levels, which provided suggestions for further investigation of molecular mechanisms underlying the toxicity induced by strobilurins on aquatic organisms.

Keywords: Cell apoptosis; Mitochondria; Oxidative stress; Strobilurins; Zebrafish.