PUBLICATION
Insights into hepatotoxicity of fluorinated liquid crystal monomer 1-ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl) benzene (EDPrB) in adult zebrafish at environmentally relevant concentrations: Metabolic disorder and stress response
- Authors
- Li, W., Wang, S., Fan, H., Wang, Z., Liu, Y., You, H.
- ID
- ZDB-PUB-250109-115
- Date
- 2024
- Source
- Journal of hazardous materials 486: 136858136858 (Journal)
- Registered Authors
- Keywords
- 1-Ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl) benzene (EDPrB), Fluorinated liquid crystal monomers (FLCMs), Hepatotoxicity, Metabolic disorder, Zebrafish
- MeSH Terms
-
- Stress, Physiological/drug effects
- Zebrafish*
- Liquid Crystals/chemistry
- Chemical and Drug Induced Liver Injury/metabolism
- Molecular Docking Simulation
- Water Pollutants, Chemical/toxicity
- Lipid Metabolism/drug effects
- Animals
- Liver*/drug effects
- Liver*/metabolism
- PubMed
- 39742860 Full text @ J. Hazard. Mater.
Citation
Li, W., Wang, S., Fan, H., Wang, Z., Liu, Y., You, H. (2024) Insights into hepatotoxicity of fluorinated liquid crystal monomer 1-ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl) benzene (EDPrB) in adult zebrafish at environmentally relevant concentrations: Metabolic disorder and stress response. Journal of hazardous materials. 486:136858136858.
Abstract
Fluorinated liquid crystal monomers (FLCMs) are widely employed in liquid crystal display (LCD) panels. As emerging environmental contaminants with persistent, bioaccumulative, and toxic properties, FLCMs were proven to accumulate in liver, raising great concern regarding potential hepatotoxicity. 1-Ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl) benzene (EDPrB), as one representative FLCM, was chosen to investigate the hepatotoxicity in adult zebrafish (Danio rerio) at environmentally relevant concentrations (1, 10, and 100 μg/L) with long-term exposure (21 days). EDPrB caused morphological abnormalities, elevated transaminase activities, and inhibited antioxidant levels in zebrafish liver. The contents of total cholesterol and triglyceride were reduced by 2.3- and 1.82-fold, respectively, at 100 μg/L of EDPrB. Transcriptomic analysis revealed that EDPrB disrupted the lipid and glucose metabolisms, protein processing in endoplasmic reticulum (ER), and P53 signal pathway by dysregulating genes, such as fasn, acaca, acsl1b, hkdc1, xbp1, and ero1lb. EDPrB induced ER stress by activating PERK-eIF2α pathway, leading to hepatic metabolic dysfunction. PERK-eIF2α and P53-Bax/Bcl2 pathways were involved in EDPrB-induced apoptosis. Additionally, molecular simulation confirmed that EDPrB had a strong binding affinity to some lipid metabolism proteins (-8.9∼-6.7 kcal/mol) and stress proteins (-9.3∼-5.8 kcal/mol). The findings elucidate EDPrB-induced hepatotoxicity and underlying mechanisms, which contribute to assessing the ecological risk and pollution control of FLCMs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping