Northeast Agricultural University, Harbin 150030, PR China.
Institute of Crop Cultivation and Tillage, Heilongjiang Academy of Agricultural Sciences, Harbin 150086, PR China.
Pestic Biochem Physiol. 2024 Aug;203:106017. doi: 10.1016/j.pestbp.2024.106017. Epub 2024 Jul 6.
Emamectin benzoate (EMB), commonly used as an insecticide in fishery production, inevitably leaves residual chemicals in aquatic environments. High-level EMB exposure can cause severe damage to multiple systems of marine animals, potentially through mechanisms involving severe mitochondrial damage and oxidative stress. However, it is not clear yet how EMB exposure at a certain level can cause damage to fish kidney tissue. In this study, we exposed carps to an aquatic environment containing 2.4 μg/L of EMB and cultured carp kidney cells in vitro, established a cell model exposed to EMB. Our findings revealed that EMB exposure resulted in severe kidney tissue damage in carp and compromised the viability of grass carp kidney cells (CIK cells). By RNA-seq analysis, EMB exposure led to significant differences in mitochondrial homeostasis, response to ROS, ferroptosis, and autophagy signals in carp kidney tissue. Mechanistically, EMB exposure induced mitochondrial oxidative stress by promoting the generation of mitochondrial superoxide and reducing the activity of antioxidant enzymes. Additionally, EMB exposure triggered loss of mitochondrial membrane potential, an imbalance in mitochondrial fusion/division homeostasis, and dysfunction in oxidative phosphorylation, ultimately impairing ATP synthesis. Notably, EMB exposure also accelerated excessive autophagy and ferroptosis of cells by contributing to the formation of lipid peroxides and autophagosomes, and the deposition of Fe. However, N-acetyl-L-cysteine (NAC) treatment alleviated the damage and death of CIK cells by inhibiting oxidative stress. Overall, our study demonstrated that EMB exposure induced mitochondrial oxidative stress, impaired mitochondrial homeostasis, and function, promoted autophagy and ferroptosis of kidney cells, and ultimately led to kidney tissue damage in carp. Our research enhanced the toxicological understanding on EMB exposure and provides a model reference for comparative medicine.
苯甲酸盐（EMB）是一种常用的杀虫剂，在渔业生产中不可避免地会在水生环境中残留化学物质。高水平的 EMB 暴露会对海洋动物的多个系统造成严重损害，其潜在机制可能涉及严重的线粒体损伤和氧化应激。然而，目前尚不清楚 EMB 在一定水平下的暴露如何会对鱼类肾脏组织造成损害。在本研究中，我们将鲤鱼暴露于含有 2.4μg/L EMB 的水生环境中，并在体外培养鲤鱼肾脏细胞，建立了 EMB 暴露的细胞模型。我们的研究结果表明，EMB 暴露会导致鲤鱼肾脏组织严重损伤，并降低草鱼肾脏细胞（CIK 细胞）的活力。通过 RNA-seq 分析，EMB 暴露导致鲤鱼肾脏组织中线粒体稳态、ROS 反应、铁死亡和自噬信号的显著差异。在机制上，EMB 暴露通过促进线粒体超氧阴离子的产生和降低抗氧化酶的活性来诱导线粒体氧化应激。此外，EMB 暴露还触发了线粒体膜电位的丧失、线粒体融合/分裂平衡的失衡以及氧化磷酸化功能的障碍，最终损害了 ATP 的合成。值得注意的是，EMB 暴露还通过促进脂质过氧化物和自噬体的形成以及 Fe 的沉积，加速了细胞的过度自噬和铁死亡。然而，N-乙酰-L-半胱氨酸（NAC）处理通过抑制氧化应激缓解了 CIK 细胞的损伤和死亡。总的来说，我们的研究表明，EMB 暴露诱导了线粒体氧化应激，破坏了线粒体的稳态和功能，促进了肾脏细胞的自噬和铁死亡，最终导致了鲤鱼肾脏组织的损伤。我们的研究增强了对 EMB 暴露的毒理学认识，并为比较医学提供了模型参考。
