分离肠道酶转化在调节内部暴露三大酸盐中的作用
Min Liu1,2, Shenhong Wang3, Xing Chen4
1School of Civil and Environmental Engineering, Nanyang Technological University, Singapore 639798, Singapore.
Environmental science & technology
|April 14, 2025
概括
胃肠道 (GIT) 显著地代谢了像DBP和DEHP (>90%) 这样的酸盐,从而降低了它们的生物可用性. 这凸显了GIT在甲酸盐暴露和健康风险评估方面的关键作用.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 药理动力学 药理动力学
背景情况:
- 酸盐是广泛存在的环境污染物,与健康风险有关.
- 精确的人类暴露评估受到复杂的甲酸代谢和质量平衡差距的阻碍.
- 与肝脏相比,胃肠道 (GIT) 在酸盐代谢中的作用尚未得到充分研究.
研究的目的:
- 在GIT中调查二甲酸 (DBP),二2-乙甲酸 (DEHP) 和二甲酸 (DEP) 的新陈代谢.
- 为了确定在模拟的胃肠液中负责甲酸盐水解的酶.
- 量化肠道和肝脏新陈代谢对甲酸体负担的相对贡献,使用基于生理学的毒动力学模型.
主要方法:
- 在模拟的胃和小肠液体中化甲酸灭菌剂.
- 在不同的pH条件下 (4.07.5) 进行甲酸盐水解的动态分析.
- 应用精细的人体生理学基础的毒动力学模型来评估吸收前肠道与吸收后肝脏生物转化.
主要成果:
- DBP和DEHP在GIT中被广泛代谢 (>90%),主要是通过脂酶,肝脏参与最小.
- 在GIT中,DEP显示出有限的预吸收代谢 (13%) .
- 结构依赖的差异显著影响GIT中的甲酸代谢率.
结论:
- GIT在通过广泛的前吸收代谢来限制酸盐的生物可用性方面发挥着至关重要的作用.
- 考虑到肠道第一通效应对于准确的甲酸盐毒动力学建模至关重要.
- GIT代谢显著影响着甲酸盐的药理动力学和相关健康风险的预测.
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