和多基基物质 (PFAS) 与血清蛋白质的结合:对人类毒动力学的影响
Fabian Christoph Fischer1, Sophia Ludtke1, Colin Thackray1
1Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, United States.
和多醇基物质 (PFAS) 与人血清蛋白质结合,影响其毒性和消除. 这项研究量化了PFAS与白蛋白和球蛋白的结合,揭示了显著的个体变异性.
科学领域:
- 环境化学环境化学
- 毒理学 毒理学 毒理学
- 生物化学 生物化学
背景情况:
- 和多醇基物质 (PFAS) 是大多数人体血清中发现的持久性环境污染物.
- 暴露于PFAS与不良健康结果有关,包括免疫毒性,癌症和代谢干扰.
- PFAS与人血清白蛋白 (HSA) 和血球蛋白等血清蛋白结合,影响它们的生物命运和毒性.
研究的目的:
- 研究各种PFAS在人血清中与HSA和血球蛋白的竞争性结合.
- 量化 PFAS 与 HSA 和球蛋白结合的分布系数 (D 值).
- 评估蛋白质结合对人类血清中未结合的PFAS度变化的影响.
主要方法:
- 使用C18固相微提取纤维测量HSA-水和球蛋白-水分布系数 (D值).
- 分析的PFAS具有不同的完全化碳链长度 (ηpfc = 4-13) 和功能头组.
- 纳入实验测量的D值和血清蛋白度,以预测PFAS在人血清中的结合.
主要成果:
- 具有较短的完全化链 (ηpfc < 7) 的PFAS优先与HSA结合.
- 具有较长 perfluorinated 链的 PFAS (ηpfc ≥7) 对球蛋白的亲和力更大.
- 实验确定的结合参数准确预测了PFAS血清结合的变异性,未结合的分数在个体之间变化高达2.5倍.
结论:
- 血清蛋白结合,特别是HSA和球蛋白,是影响PFAS药理动力学和毒力学的一个关键因素.
- 血清蛋白度和PFAS结合亲缘关系的个体差异对内部PFAS暴露的变化有显著的贡献.
- 在调查PFAS暴露对健康的影响的流行病学研究中,HSA和球蛋白应该被视为重要的共同变量.
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