不同的体外肝脏模型揭示了四博二甲的全面生物转化途径
Hongrui Zhang1, Xingwang Hou2, Jiyan Liu3
1State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, Beijing 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China.
Environment international
|October 14, 2025
概括
在人类肝脏模型中,四博二甲 (TBBPA) 的新陈代谢有所不同. 研究人员确定了21种TBBPA代谢物,包括一种新型化合物,揭示了复杂的生物转化途径.
科学领域:
- 环境化学环境化学
- 毒理学 毒理学 毒理学
- 人类的新陈代谢.
背景情况:
- 二甲 (TBBPA) 是一种普遍存在的制阻燃剂.
- 人们对TBBPA在人肝中的生物转化及其对环境和健康的影响存在担忧.
研究的目的:
- 为了研究和比较三种不同的体外人肝模型中TBBPA的代谢:人肝显微体 (HLM),HepG2细胞和MIHA细胞.
- 为了识别TBBPA代谢物并阐明其在人类肝脏系统中的转化途径.
主要方法:
- 使用了三个体外肝脏模型:HLM,HepG2细胞和MIHA细胞用于TBBPA暴露.
- 采用非目标分析来识别和量化TBBPA代谢物.
- 在不同模型中比较新陈代谢效率和代谢物概况.
主要成果:
- 观察到TBBPA代谢率的显著差异:HLM中的92.4%,HepG2细胞中的13.6%,MIHA细胞中的98.4%.
- 总共有21种TBBPA代谢物被确定,其中7种在HLM细胞中,9种在HepG2细胞中,16种在MIHA细胞中.
- 发现了一种新型代谢物,即TBBPA单β-d-glucopyranoside单β-d-glucuronide.
结论:
- 在HLM,HepG2和MIHA模型中,TBBPA的代谢程度和代谢物概况显著不同,这可能是由于酶表达和活性的变化.
- 通过整合三种模型的数据,复杂的TBBPA转化途径,包括葡萄糖化,硫化和除,得到了确认.
- 这种全面的理解有助于评估与人类TBBPA暴露相关的环境命运和健康风险.
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