Liver injury may cause many diseases, such as non-alcoholic fatty liver disease (NAFLD). Acetochlor is one of the representative chloroacetamide herbicides, and its metabolite 2-chloro-N-(2-ethyl-6-methyl phenyl) acetamide (CMEPA) is the main form of exposure in the environment. It has been shown that acetochlor can cause mitochondrial damage of HepG2 cells and induce apoptosis by activating Bcl/Bax pathway (Wang et al., 2021). But there has been less research on CMEPA. we explored the possibility of CMEPA and liver injury through biological experiments. In vivo, CMEPA (0–16 mg/L) induced liver damage in zebrafish larvae, including increased lipid droplets, changes in liver morphology (>1.3-fold) and increased TC/TG content (>2.5-fold). In vitro, we selected L02 (human normal liver cells) as the model, and explored its molecular mechanism. We found that CMEPA (0–160 mg/L) induced apoptosis (similar to 40%), mitochondrial damage and oxidative stress in L02 cells. CMEPA induced intracellular lipid accumulation by inhibiting AMPK/ACC/CPT-1A signaling pathway and activating SREBP-1c/FAS signaling pathway. Our study provides evidence of a link between CMEPA and liver injury. This raises concerns regarding the health risks of pesticide metabolites to liver health.

肝损伤可能导致许多疾病，例如非酒精性脂肪性肝病（NAFLD）。乙草胺是代表性的氯乙酰胺类除草剂之一，其代谢产物2-氯-N-(2-乙基-6-甲基苯基)乙酰胺(CMEPA)是其在环境中的主要暴露形式。已有研究表明，乙草胺可引起 HepG2 细胞线粒体损伤，并通过激活 Bcl/Bax 通路诱导细胞凋亡 (Wang et al., 2021)。但对 CMEPA 的研究较少。我们通过生物学实验探讨了CMEPA与肝损伤的可能性。在体内，CMEPA (0–16 mg/L) 诱导斑马鱼幼体肝损伤，包括脂滴增加、肝脏形态变化（>1.3 倍）和 TC/TG 含量增加（>2.5 倍）。体外_，我们选择L02（人类正常肝细胞）作为模型，探索其分子机制。我们发现 CMEPA (0–160 mg/L) 在 L02 细胞中诱导细胞凋亡（类似于 40%）、线粒体损伤和氧化应激。CMEPA通过抑制AMPK/ACC/CPT-1A信号通路和激活SREBP-1c/FAS信号通路诱导细胞内脂质积累。我们的研究提供了 CMEPA 与肝损伤之间联系的证据。这引起了人们对农药代谢物对肝脏健康的健康风险的担忧。