Effects of tetrabromobisphenol A on ionizing radiation-induced liver toxicity in zebrafish
10.3760/cma.j.cn112271-20231205-00199
- VernacularTitle:四溴双酚A对电离辐射诱导的斑马鱼肝脏毒性效应的影响
- Author:
Shuqin ZHANG
1
;
Yue SHANG
;
Yajia CHENG
;
Tong ZHU
;
Zhouxuan WANG
;
Saijun FAN
Author Information
1. 中国医学科学院北京协和医学院放射医学研究所 天津市放射医学与分子核医学重点实验室，天津 300192
- Keywords:
Tetrabromobisphenol A;
γ-ray;
Zebrafish;
Liver toxicity;
Metabolome
- From:
Chinese Journal of Radiological Medicine and Protection
2024;44(7):578-586
- CountryChina
- Language:Chinese
-
Abstract:
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.
