Carcinogenesis, Teratogenesis & Mutagenesis ›› 2026, Vol. 38 ›› Issue (2): 128-136.doi: 10.3969/j.issn.1004-616x.2026.02.007

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Environmentally relevant concentrations of triethyl phosphate exposure on liver toxicity in zebrafish and its molecular mechanism

WU Pingfan1,2, MA Xue1,2, ZENG Xiaoqi1,2,3, ZHU Qiang1,2, HUANG Qiyan1,2, LI Hongmei1,2,3, XU Haiming1,2   

  1. 1. School of Public Health, Ningxia Medical University, Yinchuan 750004;
    2. Ningxia Key Laboratory of Environmental Factors and Chronic Disease Control, Yinchuan 750004;
    3. Key Laboratory of Fertility Preservation and Maintenance of Ningxia Medical University, Yinchuan 750004, Ningxia, China
  • Received:2025-11-27 Revised:2026-02-08 Published:2026-04-09

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Abstract: OBJECTIVE: This study aimed to investigate liver toxicity of the organophosphate flame retardant triethyl phosphate(TEP) on zebrafish(Danio rerio), and to provide a scientific basis for the ecological risk assessment of TEP. METHODS: Four-month-old AB strain wild-type zebrafish were exposed to environmentally relevant concentrations of TEP(0, 1, 10, 100, and 1 000 μg/L) for 28 days. After exposure,body weight and body length were measured. Histopathological damage of the liver was observed via hematoxylin-eosin(HE) staining. Liver function indicators(activities of ALT and AST), oxidative stress and inflammation-related indicators(gene expression levels and enzyme activities),metabolic enzyme(CYP450),and expression levels of key molecules in the Keap1-Nrf2-ARE signaling pathway were detected using RT-qPCR,ELISA,and other methods. RESULTS: TEP exposure had no significant effect on the body weight or body length of zebrafish. HE pathological sections of exposed groups showed sinusoidal dilation and edema in the liver;nuclear lysis was observed in the 1 and 10 μg/L TEP groups,while nuclear lysis,nuclear pyknosis,and anuclear areas were simultaneously observed in the 100 and 1 000 μg/L groups. Activities of ALT and AST were significantly elevated. The mRNA expression of oxidative stress-related genes(Sod1,Sod2,Gstp1.1,Gstp1.2, Cat, Cyp1a, Cyp3a, and Gpx1a) were downregulated, while the mRNA expression of proinflammatory factors(IL-1β,TNF-α and IL-6) was upregulated. The activities of SOD,CAT,GSH-Px,and CYP450 were significantly decreased,whereas MDA content was significantly increased. For key molecules in the Keap1-Nrf2-ARE signaling pathway:the mRNA expression of Keap1 was upregulated,while Nrf2,Ho1,and NQO1 expressions were downregulated. Meanwhile, the protein expressions of Keap1, Nrf2 and NQO1 were significantly downregulated. CONCLUSION: Environmentally relevant concentrations of TEP induced oxidative stress injury accompanied by inflammatory response in zebrafish liver by interfering with the Keap1-Nrf2-ARE signaling pathway. The results provide scientific reference for ecological prevention and control of TEP pollution in water bodies.

Key words: triethyl phosphate, zebrafish, environmentally relevant concentrations, hepatotoxicity, molecular mechanism

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