Effects of tetrabromobisphenol A on ionizing radiation-induced liver toxicity in zebrafish
Objective To investigate the effects of tetrabromobisphenol A(TBBPA)on ionizing radiation(IR)-induced liver toxicity based on a zebrafish model and provide a scientific basis for assessing microplastic-radiation exposure hazards to the survival and health of aquatic organisms and humans.Methods Healthy adult zebrafish aged 4-6 months were grouped(20 fish each group,sex in half)by random number table method in three different ways.The TBBPA exposure concentration screening experiment was divided into 4 groups:control group and TBBPA(3,30 and 300 μg/L)treatment groups.The experiment of effects of double exposure on liver function was divided into 5 groups:control group,IR(10,20 or 30 Gy)groups and IR+TBBPA(60,300 and 1 500 μg/L)treatment groups.The experiment of effects of TBBPA on hepatic radiation toxicity was divided into 3 groups:control group,IR(20 Gy)group,and IR+TBBPA(300 μg/L)group.The changes in liver function indexes,oxidative stress markers,pro-inflammatory cytokines,and liver cell apoptosis were monitored,differential metabolic pathways and metabolites were identified upon untargeted metabolomics assays,and inter-group data were compared by One-way ANOVA test.Results The activities of ALT and AST in zebrafish liver increased in a dose-dependent manner after exposure to TBBPA,and the differences between 300 μg/L TBBPA group and control group were statistically significant(t=-2.22,-3.20,P＜0.05).IR at a dose of 20 Gy or above induced a significant decline of liver function,and at this radiation dose,combined exposure to 300 μg/L or above TBBPA intensified the liver toxicity(compared with the control group,t=-8.18 to-4.63,P＜0.05,compared with IR group,t=-5.22 to-0.30,P＜0.05).Compared with the control group,the activities of ALT and AST,levels of ROS,MDA and SOD,mRNA and protein expression levels of TNF-α,IL-1β,Cox-2,Caspase-8 and Caspase-9,and cell apoptosis in zebrafish livers of IR and IR+TBBPA groups increased gradually(compared with the control group,t=-12.29 to-2.88,P＜0.05,compared with IR group,t=-4.40 to-2.31,P＜0.05).The differences in the content of D-gluconic acid,p-cresol and other metabolites in liver tissues were more and more significant among the three groups,involving multiple KEGG pathways such as biosynthesis,degradation and metabolism.Conclusions Exposure to 300 μg/L TBBPA can aggravate IR-induced liver toxicity of zebrafish,which involves the mechanism that further elevates the levels of oxidative stress,inflammation,and apoptosis,as well as radiation-induced liver metabolic disorders.
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