以LC-ICP-MS为基础的L-氨酸化试验进行体外铁氧化酶抑制的评估:与AMPLEX超红色试验及其修改进行比较
Runze Liu1, Jiří Novák1, Jan Kuta1
1Faculty of Science, RECETOX, Masaryk University, Kamenice 753/5, pavilion A29, 625 00, Brno, Czech Republic.
Archives of toxicology
|January 14, 2026
概括
环境中的化学物质会破坏甲状腺激素 (TH) 系统. 氨酸化 (Tyr-I) 测定比Amplex UltraRed (AUR) 更敏感,用于检测甲状腺过氧化酶 (TPO) 抑制,这对于评估化学风险至关重要.
科学领域:
- 环境毒理学环境毒理学
- 内分泌学 在内分泌学.
- 测试开发的发展.
背景情况:
- 环境化学物质可以破坏甲状腺激素 (TH) 系统,对人类和野生动物健康构成风险.
- 甲状腺过氧化酶 (TPO) 抑制是破坏TH合成的关键机制.
- 需要遵守3R原则的体外测试来评估TPO抑制.
研究的目的:
- 为了比较TPO抑制的两个体外试验的灵敏度和特异性.
- 评估21种不同的化学物质的TPO抑制潜力.
- 为评估TH系统破坏性化学品提供科学合理的方法.
主要方法:
- 氨酸化 (Tyr-I) 试验 (HPLC-ICP-MS) 和Amplex UltraRed (AUR) 试验及其修改的比较.
- 使用人类HEK-TPOA7细胞和老鼠甲状腺显微体进行测试.
- 在0.002200μM的度范围内对21种化学物质的评估.
主要成果:
- 泰尔-I试验表现出卓越的灵敏度,检测出TPO活性的过氧化和化步骤.
- 对于一些与人类暴露相关的化学物质,使用Tyr-I.I.的有效度在1574nM范围内.
- 仅检测过氧化的AUR试验显示,对化 (NaI) 的敏感度提高,但仍然比Tyr-I.敏感度低.
结论:
- 与AUR测定相比,Tyr-I测定是评估TPO抑制的更敏感的方法.
- 该研究强调了TPO抑制测试中不同测试变体的优点和局限性.
- 这项研究支持开发有效的甲状腺激素破坏者的测试策略.
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