The health risk of acetochlor metabolite CMEPA is associated with lipid accumulation induced liver injury

• Published in: Environmental pollution (1987) 2023-08, Vol.331 (Pt 2), p.121857-121857, Article 121857
• Main Authors: Wang, Wei-Guo, Li, Mu-Yao, Diao, Lin, Zhang, Cheng, Tao, Li-Ming, Zhou, Wei-Xing, Xu, Wen-Ping, Zhang, Yang
• Format: Article
• Language: English
• Subjects: Acetochlor metabolite; Animals; Chemical and Drug Induced Liver Injury, Chronic - metabolism; Cytotoxicity; Humans; Lipid accumulation; Lipid Metabolism; Lipids; Liver - metabolism; Liver injury; Zebrafish
• ISSN: 0269-7491; 1873-6424
• DOI: 10.1016/j.envpol.2023.121857

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. [Display omitted] •CMEPA induced steatosis and liver morphological changes in zebrafish larvae.•CMEPA induced the increase of lipid content and TC/TG content in liver of zebrafish larvae.•CMEPA induced functional impairment and apoptosis of human liver L02 cells.•CMEPA induced oxidative stress and lipid accumulation in L02 cells.•CMEPA induced lipid accumulation via AMPK/ACC/CPT-1A and SREBP-1c/FAS pathways in L02 cells.