Microplastics (MPs) and Emamectin Benzoate (EMB) were identified as hazardous environmental pollutants, frequently coexisting in aquatic ecosystems, posing potential risk in the immune system of human and animal. However, the hazards of concurrent exposed to MPs and EMB on the carp spleen, and the specific mechanisms remain unclear. Here, we employed MPs and EMB-exposed carp models, and cultured splenocytes in vitro, to demonstrate that PPARα signals suppression underlay MPs and EMB-induced carp spleen injury, based on transcriptomics and lipomics analysis. This suppression exacerbated the buildup of polyunsaturated fatty acid (PUFA), and promoted ACSL4 expression, resulting in increased lipid peroxidation. Further studies found that the accumulation of lipid peroxides predominantly occurred in the mitochondria, which evoked mitochondrial homeostasis imbalance and compromised mitochondrial function, thereby initiating ferroptosis. Additionally, enhancing PPARα signaling, inhibiting ACSL4, or scavenging mitochondrial ROS was favor of mitigating accumulation of lipid peroxides, reducing mitochondrial damage and inhibiting ferroptosis. Notably, MPs and EMB co-exposure caused more severe damage than single exposure. These findings uncovered a potential mechanism, involving PPARα signaling inhibition by MPs and EMB co-exposure, which evoked lipid remodeling and increased ACSL4, to drive ferroptosis and carp splenic injury. This study highlighted the potential hazards to the aquaculture environments where co-exposure of MPs and EMB and provided reference for environmental toxicology research and the sustainable development of the aquaculture industry.
Pan Enzhuang,Xin Yue,Li Xueqing,Ping Kaixin,Li Xing,Sun Ying,Xu Xuhui,Dong Jingquan
As a broad-spectrum and efficient triazole fungicide, difenoconazole is widely used, which not only pollutes the environment but also exerts toxic effects on non-target organisms. The spleen plays an important role in immune protection as an important secondary lymphoid organ in carp. In this study, we assessed the protective impact of silybin as a dietary additive on spleen tissues of carp during exposure to difenoconazole. Sixty carp were separated into four groups for this investigation including control group, difenoconazole group, silybin group, and silybin and difenoconazole group. By hematoxylin-eosin staining, dihydroethidium staining, immunohistochemical staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, quantitative real-time PCR assay, Western blot analysis, biochemical assays, and immune function indicator assays, we found that silybin could prevent difenoconazole-induced spleen tissue damage, oxidative stress, and immune dysfunction, and inhibited apoptosis of carp spleen tissue cells by suppressing the formation of p53-driven caspase-9-apoptotic protease activating factor-1-cytochrome C complex. The results suggested that silybin as a dietary additive could improve spleen tissue damage and immune dysfunction induced by difenoconazole in aquaculture carp.
危险品化学品经营许可证（带存储）