JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Wanlun Li,Shutao Wang,Huize Fan,Ziwei Wang,Yingying Liu,Hong You
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.
研究领域:
环境科学
·
毒理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2026
·Vol. 60
·期 30
·20825-20842
·
IF 12.2
Miao Chenjiao,Zhang Binwen,Yu Wangyong,Li Yanfei,Cao Zheng
1-Ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl) benzene
(EDPrB),
a highly polluting fluorinated liquid-crystal monomers (FLCMs), accumulates
in the kidneys over the long term. First, our study demonstrates that
exposure to EDPrB can induce inflammatory responses and fibrosis in
human renal cortical proximal tubule epithelial cells (HK-2), posing
a risk of nephrotoxicity. Next, our study investigates the renal injury
induced by EDPrB in male Kunming mice after 70-day exposure at 13,
130, and 1300 μg/kg bw/day, using an adverse outcome pathway
(AOP) framework. Histopathological observations demonstrate that EDPrB
corresponds to an elevated probability of developing chronic kidney
disease (CKD). Proteomics and Western blot analysis revealed that
mTOR signaling may be the mechanism by which EDPrB induces CKD in
mice and causes damage to HK-2 cells. Finally, by treating EDPrB-exposed
mice with RAPA, we demonstrated that activation of the mTOR signaling
is the molecular initiating event driving EDPrB-induced CKD in mice.
This study proposes an AOP framework focused on EDPrB-induced CKD.
The molecular initiating event is identified as mTOR activation, followed
by autophagy inhibition leading to inflammation and fibrosis as key
events, ultimately resulting in CKD as an adverse outcome. This highlights
the renal risks of FLCMs and supports stricter environmental release
regulations.
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PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2026
·
IF 3.6
Wanlun Li,Shutao Wang,Ziwei Wang,Huize Fan,Hong You
Fluorinated liquid crystal monomers (FLCMs) are widely used in liquid crystal display (LCD) panels. However, as emerging contaminants, FLCMs have been detected in various environments and proven to be toxic to humans. This study aimed to investigate the molecular mechanisms underlying the hepatotoxicity of a typical FLCM, 1-ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl) benzene (EDPrB), in HepG2 cells. EDPrB exposure (25 mg/L) induced oxidative stress, evidenced by reduced CAT activity (1.87-fold) and increased MDA content (2.12-fold) ( p < 0.05). 25 mg/L EDPrB disrupted the metabolism, significantly elevating the levels of TC (1.65-fold, p < 0.001), TG (1.47-fold, p < 0.01), and GLU (1.44-fold, p < 0.05), respectively. Comprehensive analysis of transcriptomics and metabolomics revealed that EDPrB affected lipid and glucose metabolisms, antioxidant defense-related pathways, and PI3K/AKT/mTOR signaling pathways. Additionally, the altered expression of metabolism-related genes confirmed the promotion of fatty acid synthesis and glycolysis. The altered expression of PI3K, AKT, and mTOR proteins, coupled with their strong binding affinity to EDPrB, collectively revealed the dysregulation of PI3K/AKT/mTOR pathways. Protein-protein interaction (PPI) analysis further verified the interaction between lipid and glucose metabolism disorders, oxidative stress, and PI3K/AKT/mTOR pathways dysfunction, contributing to EDPrB-induced hepatotoxicity. Our findings provide valuable insights into the potential health risks of FLCMs.
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PubMed
高影响因子
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