环境相关浓度磷酸三乙酯暴露对斑马鱼肝脏的毒性及其分子机制OA

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 pro-inflammatory 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.