Engineering Research Center for Medicine, Ministry of Education, Harbin University of Commerce, 138 Tongda Street, Daoli District, Harbin 150076, China.
Engineering Research Center for Medicine, Ministry of Education, Harbin University of Commerce, 138 Tongda Street, Daoli District, Harbin 150076, China.
Ecotoxicol Environ Saf. 2022 Nov;246:114186. doi: 10.1016/j.ecoenv.2022.114186. Epub 2022 Oct 13.
Tri-(2,3-dibromopropyl) isocyanate (TBC), a newly brominated flame retardant, is widely used in the synthesis of flame retardant materials with characteristics of persistent organic pollutants. To obtain environmental exposure risks of TBC, Wistar rats and HepG2 cell were used for in vivo and in vitro studies on the toxicity of TBC and relevant ecotoxicological mechanisms of apoptosis. 80 Wistar rats were randomly selected and divided into four exposure groups (0, 0.313, 0.625, 1.250) g/(kg·bw) TBC, half male and half female, with oral administration for 28 days. Wistar rats exhibited appetite loss, weight loss, and dull hair with increasing period of TBC exposure. The pathological examinations revealed the most severe damage of liver and the ratio of liver/body weight of 35.497 × 10 for high-dosed group (1.250 g/kg·bw) was higher than that of 32.792 × 10 for control group in female rats with identical trend in male rats. The above indicators was fairly consistent with the serum test results which further confirmed the liver to be the target organ. The exposure dosages of HepG2 cell were (0, 12.5, 25, 50) μg/mL, individually. The HepG2 cells exposed to TBC for 72 h displayed hazy cell contour and decreased density of cell growth. And there was an inhibition detected by MTT assay, where the maximum inhibition rate was 19.93% under the dose of 50 μg/mL TBC. Apoptosis rate detected by flow cytometry which was demonstrated to be positively correlated to exposure dosage of TBC. The apoptosis rates of the low, medium and high dose groups of TBC exposure were (1.082 ± 0.109) %, (3.017 ± 0.09) % and (6.813 ± 0.233) %, individually. Targeted genes and corresponding protein expressions that triggering apoptosis both in vivo and in vitro were significantly altered. Overall, this work discloses the impacts of TBC exposure on hepatotoxicity, which provides new insights for chemical risk assessments of accelerate cell apoptosis via mitochondrial and death receptor pathway.
三（2,3-二溴丙基）异氰酸酯（TBC）是一种新型溴化阻燃剂，广泛用于合成具有持久性有机污染物特性的阻燃材料。为了获得 TBC 的环境暴露风险，本研究使用 Wistar 大鼠和 HepG2 细胞进行了 TBC 毒性的体内和体外研究，并探讨了相关的细胞凋亡生态毒理学机制。
将 80 只 Wistar 大鼠随机分为 4 个暴露组（0、0.313、0.625、1.250）g/（kg·bw）TBC，雌雄各半，经口染毒 28 天。随着 TBC 暴露时间的延长，Wistar 大鼠出现摄食量下降、体重减轻、毛发无光泽等现象。病理检查结果显示，高剂量组（1.250 g/kg·bw）雄性和雌性大鼠的肝脏损伤最严重，肝体比分别为 35.497×10 和 32.792×10，与对照组相比均有升高。血清检测结果与上述指标较为一致，进一步证实了肝脏是 TBC 的靶器官。HepG2 细胞的染毒剂量分别为（0、12.5、25、50）μg/mL。暴露于 TBC 72 h 后，HepG2 细胞轮廓模糊，细胞生长密度降低。MTT 检测显示细胞抑制率，其中 50 μg/mL TBC 组的最大抑制率为 19.93%。流式细胞术检测到细胞凋亡率与 TBC 暴露剂量呈正相关。TBC 低、中、高剂量组的细胞凋亡率分别为（1.082±0.109）%、（3.017±0.09）%和（6.813±0.233）%。体内和体外实验均显示，TBC 暴露导致靶向基因和相应蛋白表达发生显著改变，进而引发细胞凋亡。
综上所述，本研究揭示了 TBC 暴露对肝毒性的影响，为通过线粒体和死亡受体途径加速细胞凋亡的化学风险评估提供了新的见解。
