Mechanisms regarding respiratory toxicity triggered by accumulation of ROS in carp exposed to difenoconazole

Difenoconazole is a widely used but difficult-to-degrade fungicide that can directly affect aquatic ecosystems. Here, two doses (0.488 mg/L, 1.953 mg/L) of difenoconazole were used to study the toxicity to the respiratory system of carp at an exposure time of 96 h. The results showed that difenoconazole exposure resulted in severe structural damage to carp gill tissue with extensive inflammatory cell infiltration. Mechanistically, difenoco-nazole exposure led to excessive accumulation of ROS in carp gill tissue, which induced an inflammatory response in the gill tissue. Meanwhile, the activities of SOD and CAT were reduced and the NRF2 signaling pathway was activated to regulate the imbalance between oxidation and antioxidation. In addition, difenoco-nazole exposure further activated the mitochondrial pathway of apoptosis by upregulating cytochrome C, BAX, cleaved-caspase 9, and downregulating Bcl-2. More interestingly, exposure to difenoconazole increased auto-phagosomes, but lysosomal dysfunction prevented the late stages of autophagy from proceeding smoothly, resulting in a protective autophagic response that is not properly initiated. In summary, difenoconazole exposure caused respiratory toxicity including inflammation response, oxidative stress, apoptosis, and autophagy in carp through the accumulation of ROS. The present study expanded our understanding of the toxic effects of dife-noconazole on organisms and its possible threat to the aquatic environment.

Automated summary

In this study, the respiratory toxicity of difenoconazole to carp was investigated. Exposure to difenoconazole caused severe damage to carp gill tissue and induced an inflammatory response. Additionally, difenoconazole exposure led to oxidative stress, apoptosis, and disrupted autophagy. These findings enhance our understanding of the toxic effects of difenoconazole on organisms and its potential threat to the aquatic environment.