在人血清中识别化化胺及其潜在的代谢途径
Juntao Cui1, Rui Hua2, Yang Wu1
1State Key Laboratory of Advanced Environmental Technology, Guangdong Key Laboratory of Environment Protection and Resource Utilization, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou, Guangdong 510640, People's Republic of China.
短链和中链甲 (SCCP和MCCP) 在人体中代谢,形成化甲 (OH-CPs). 这些代谢物显示出分布的改变,并通过氧化途径形成,这表明潜在的健康影响.
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:
- 短链和中链甲 (SCCP和MCCP) 是人类群体中发现的普遍环境污染物.
- 关于SCCP和MCCP在人类中的特定代谢物的数据有限,这阻碍了对其毒理学特征的充分理解.
研究的目的:
- 在人血清中识别和量化SCCP和MCCP的代谢物.
- 通过体外人肝酶测定来研究SCCP和MCCP的代谢途径.
- 描述基因化合物及其代谢物之间的结构差异,特别是的分布.
主要方法:
- 使用UHPLC-Orbitrap-HRMS分析血清样本,以对化 (CPs) 和其代谢物进行标和非标查.
- 用人肝细胞染色体P450 (CYP) 酶进行了体外化试验,使用商业CP混合物和特定的CP单体.
- 代谢物识别以化模式和结构阐明为指导.
主要成果:
- 人体血清中SCCP和MCCP的中位数度分别为7.76和4.31 ng/mL.
- 一系列的化化 (OH-CPs) 暂时被确定,平均为1.80 ng/mL (占CP总量的9.9%).
- 从原始CP (Cl6-Cl7) 到OH-CP (Cl4-Cl6) 观察到分布的转变,体外研究证实了通过氧化脱和化,CP的代谢转化为OH-CP和碳素酸.
结论:
- 人体血清和体外数据强烈表明,SCCP和MCCP在人类中的氧化代谢产生OH-CPs.
- 代谢途径包括化和随后的氧化到碳酸盐酸,与改变的替代模式.
- 需要进一步的研究来评估这些已识别的OH-CP代谢物的长期毒性.
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