| Zhang Shuqin,Shang Yue,Cheng Yajia,et al.Effects of tetrabromobisphenol A on ionizing radiation-induced liver toxicity in zebrafish[J].Chinese Journal of Radiological Medicine and Protection,2024,44(7):578-586 |
| Effects of tetrabromobisphenol A on ionizing radiation-induced liver toxicity in zebrafish |
| Received:December 05, 2023 |
| DOI：10.3760/cma.j.cn112271-20231205-00199 |
| KeyWords:Tetrabromobisphenol A γ-ray Zebrafish Liver toxicity Metabolome |
| FundProject:国家自然科学基金(82273577,82173467);中国医学科学院医学与健康科技创新工程(CIFMS,2021-I2M-1-042,2022-I2M-2-003) |
| Author Name | Affiliation | E-mail | | Zhang Shuqin | Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China | | | Shang Yue | Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China | | | Cheng Yajia | Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China | | | Zhu Tong | Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China | | | Wang Zhouxuan | Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China | | | Fan Saijun | Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China | fansaijun@irm-cams.ac.cn |
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| 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 1500 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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