Overuse of acetochlor pollutes soil and rivers, causing threats to the ecosystem. Studies found that acetochlor exposure could damage multiple organs and tissues in fish and mammal. Tea polyphenols (TP), a natural antioxidant that extracted from tea, has been widely used in food and feed additions. However, the mechanism by which acetochlor causes tissue damage is unclear, and its mitigating agent has yet to be developed. Therefore, we established acetochlor exposure and TP mitigation models by treating Ctenopharyngodon idellus kidney (CIK) cells with 20 μM acetochlor and/or 2.5 μg/mL TP for 24 h, and detected the programmed cell death and its related pathways. The results showed that acetochlor exposure modified antioxidant enzyme activities, induced oxidative stress, resulted in the decline of MMP and ATP levels, enhanced glycolysis and lactate accumulation, and triggered apoptosis and necroptosis in CIK cells. However, TP could inhibit CYP450s expression, activate Nrf2 pathway, enhance antioxidant capacity, further effectively alleviate acetochlor-induced CIK cell death. Overall, the present study proved that acetochlor exposure triggered mitochondrial damage and lactate accumulation-mediated apoptosis and necroptosis through CYP450s/ROS/MAPK/NF-κB pathway. Furthermore, TP could alleviate effectively cell death through relieving oxidative stress and lightening Warburg-like effect.

乙草胺的过度使用会污染土壤和河流，对生态系统造成威胁。研究发现，乙草胺暴露会损害鱼类和哺乳动物的多个器官和组织。茶多酚（TP）是一种从茶叶中提取的天然抗氧化剂，已广泛用于食品和饲料添加剂。然而，乙草胺引起组织损伤的机制尚不清楚，其缓解剂尚待开发。因此，我们通过治疗idellus Ctenopharyngodon建立了乙草胺暴露和 TP 缓解模型用 20 μM 乙草胺和/或 2.5 μg/mL TP 处理肾（CIK）细胞 24 h，并检测程序性细胞死亡及其相关途径。结果表明，乙草胺暴露改变了抗氧化酶活性，诱导氧化应激，导致MMP和ATP水平下降，糖酵解和乳酸积累增强，并引发CIK细胞凋亡和坏死性凋亡。而TP可以抑制CYP450s的表达，激活Nrf2通路，增强抗氧化能力，进一步有效缓解乙草胺诱导的CIK细胞死亡。总体而言，本研究证明，乙草胺暴露通过 CYP450s/ROS/MAPK/NF-κB 通路触发线粒体损伤和乳酸积累介导的细胞凋亡和坏死性凋亡。此外，