PUBLICATION

Hepatic effects of acetochlor chiral isomers in zebrafish and L02 cells

Authors
Wang, X., Peng, B., Zhang, C., Wu, M., Xu, W., Cheng, J., Tao, L., Li, Z., Zhang, Y.
ID
ZDB-PUB-240105-26
Date
2024
Source
The Science of the total environment   913: 169781 (Journal)
Registered Authors
Wang, Xin
Keywords
Acetochlor, Isomer, L02, Liver, Zebrafish
MeSH Terms
  • Animals
  • Hepatocytes
  • Lipid Metabolism
  • Lipids
  • Liver*/metabolism
  • Toluidines*
  • Zebrafish*
PubMed
38176547 Full text @ Sci. Total Environ.
Abstract
The pesticide acetochlor (ACT) is a chiral isomer commonly detected in the global environment, yet its specific impacts on liver function remain poorly understood. We utilized zebrafish and L02 cells as research models to comprehensively investigate how ACT and its chiral isomers affect the liver. Our investigations unveiled that the R, Rac, and S isomers of ACT disrupt hepatic lipid transport, catabolism, and synthesis, leading to delayed yolk sac absorption and the accumulation of lipids in zebrafish embryos. These isomers induce oxidative stress in the liver of zebrafish embryos, reducing antioxidant levels and enzyme activity. The accumulated lipids in the liver render it susceptible to oxidative stress, further exacerbating hepatocyte damage. Hepatocyte damage manifests as extensive vacuolization of liver cells and alterations in liver morphology, which are induced by R, Rac, and S. Furthermore, we elucidated the molecular mechanisms underpinning the disturbance of hepatic lipid metabolism by R, Rac, and S in L02 cells. These compounds stimulate lipid synthesis through the upregulation of the AMPK/SREBP-1c/FAS pathway while inhibiting lipolysis via downregulation of the PPAR-α/CPT-1a pathway. Remarkably, our results highlight that S exhibits significantly higher hepatotoxicity in comparison to R. This study provides valuable insights into the hepatic effects of ACT chiral isomers.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping