在小鼠和人类中,对-和多基基物质与血蛋白结合的结构相关差异
Chloé Ml Argoul1, Pierre-Louis Toutain2, Sarah Berard3
1INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France; ToxAlim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France.
血中每和多基基物质 (PFAS) 的自由分量在人类和小鼠之间有很大的差异,特别是在短链化合物中. 这种蛋白质结合会影响PFAS的持久性,需要在健康风险评估中考虑.
科学领域:
- 环境化学环境化学
- 毒理学 毒理学 毒理学
- 药理动力学 药理动力学
背景情况:
- 和多醇基物质 (PFAS) 是具有复杂毒动力学的持久性环境污染物.
- 了解影响PFAS消除的因素,如血蛋白结合,对于准确的健康风险评估至关重要.
- 脏清除是许多PFAS的主要清除途径.
研究的目的:
- 为了研究PFAS的毒动力学,物种间的差异.
- 测量各种PFAS在人体和小鼠血中的自由 (未与蛋白质结合) 分数 (fu).
- 探索PFAS属性及其与血蛋白结合之间的基于结构的关系.
主要方法:
- 使用了Dianorm®系统来对PFAS自由分数进行稳健和快速的平衡测量.
- 测试了16种不同的PFAS化合物,包括 perfluoroalkyl carboxylic 酸 (PFCA),硫酸 (PFSA) 和以太衍生物 (PFECA).
- 在人类和小鼠血样本中量化了PFAS的未结合分数.
主要成果:
- 平均fu值显示了广泛的物种间变化,从小鼠的0.21% (PFOS) 到50% (PFPeA),人类的0.02% (PFHpS) 到8.5% (PFPeA).
- 在短链PFAS和PFECA中观察到明显的物种间差异,但在长链化合物中没有.
- 在fu和PFAS分子量之间确定了U形相关性,约有400-500g/mol的最小结合.
结论:
- 血蛋白结合是PFAS在体内持久性的关键决定因素.
- 蛋白质结合的跨物种差异显著影响PFAS毒动力学和消除率.
- 开发了预测模型,将PFAS分子量与其自由分数联系起来,有助于风险评估.
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