和多基物质与肝功能指数以及代谢机制之间的整体和个体关联
Yiran Chen1, Yan Wu2, Jiayun Lv2
1Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China; School of Public Health, Southern Medical University, Guangzhou 510515, China.
Environment international
|January 1, 2024
概括
和多基基物质 (PFAS) 混合物对肝功能产生负面影响,增加阿波利波蛋白B (APOB) 和胺转移酶 (GGT),同时降低胆红素水平. 代谢分析显示,氨基酸和甘氨酸脂路径是关键机制.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 代谢学 代谢学 代谢学
背景情况:
- 和多醇基物质 (PFAS) 是已知的破坏肝脏平衡的环境污染物.
- 虽然记录了单次PFAS暴露的影响,但较少的研究涉及PFAS混合物对肝功能的影响.
研究的目的:
- 在成年男性中调查暴露于9种PFAS和14种肝功能指数的混合物之间的关联.
- 探索 PFAS 混合物与肝功能变化的相关代谢机制.
主要方法:
- 利用非向代谢学来分析来自中国广州的278名成年男性血清代谢物概况.
- 应用了加权定量总和回归 (WQS) 和贝叶斯核机回归 (BKMR) 来评估PFAS混合物与肝功能指数之间的关联.
- 采用整个代谢组的关联和调解分析来识别介导代谢物.
主要成果:
- PFAS混合物与阿波利波蛋白B (APOB) 和胺转移酶 (GGT) 的增加以及直接胆红素 (DBIL) 和总胆红素 (TBIL) 的降低显著相关.
- 特定的PFAS如PFHxS,PFOS,PFHpS,PFNA,PFDA和PFUdA与APOB有关,而PFOA,PFDA,PFOS,PFNA和PFUdA与GT有关.
- 调解分析确定了氨基酸和甘氨酸脂代谢,特别是甘氨酸脂, (R) -dihydromaleimide,Ile Leu, (R) -(+) -2-pyrrolidone-5-carboxylic acid和L-glutamate,作为关键的调解者.
结论:
- PFAS混合物与特定的肝功能指数呈现显著关联,突出显示混合物效应的重要性.
- 已识别的代谢途径和标志物为PFAS诱导的肝功能障碍的机制提供了洞察力.
- 这些发现需要对动物模型和其他人类群体进行进一步的研究,以确认和扩展这些结果.
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