6PPD-Q的基化代谢物结构和毒性表征6PPD-Q的基化代谢物
Pranav Nair1, Holly Barrett1, Kaylin Tanoto1
1Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada.
基化N-(1,3-二甲基) -N---p-phenylenediamine-quinone (6PPD-Q) 在彩虹鱼中排毒该化合物. 三级碳C4对于新陈代谢和毒性都是关键的,氧化作为解毒途径.
科学领域:
- 环境毒理学环境毒理学
- 代谢学 代谢学 代谢学
- 生物化学 生物化学
背景情况:
- 非有毒的-p-phenylenediamine (PPD) 奇诺因与有毒的变体有所不同.
- 在彩虹鱼中,N-(1,3-dimethylbutyl) -N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) 被代谢为基化代谢物 (基-OH-6PPD-Q).
- 基-OH-6PPD-Q在6PPD-Q毒性的作用是未知的.
研究的目的:
- 合成基-OH-6PPD-Q同位素.
- 研究基-OH-6PPD-Q的代谢形成机制.
- 确定基-OH-6PPD-Q的毒性.
主要方法:
- 基-OH-6PPD-Q同位素的化学合成.
- 化6PPD-Q与彩虹鱼肝 S9 分数 (微体和细胞质).
- 使用fluoxetine (一种细胞染色体P450抑制剂) 的抑制研究.
- 使用鱼胚胎 (CSE-119) 细胞系进行细胞毒性测定.
- 从彩虹鱼肝脏显微体中分解6PPD-Q代谢物.
主要成果:
- 主要代谢物是C4-OH-6PPD-Q,在C4三级碳上化.
- 细胞染色体P450酶催化了C4-OH-6PPD-Q的形成.
- 与6PPD-Q和C3-OH-6PPD-Q不同的是,C4-OH-6PPD-Q没有表现出细胞毒性.
- 在体内的代谢物分量证实C4-OH-6PPD-Q不是细胞毒性.
结论:
- C4三级碳对6PPD-Q的新陈代谢和毒性都至关重要.
- 6PPD-Q的基氧化是一种解毒途径.
- 了解这些途径对于评估PPD衍生品对环境的风险至关重要.
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