火灾中的线粒体:制阻燃剂的毒理机制
Raul Ghiraldelli Miranda1,2, Ivo F Machado3,4,5, Anabela Pinto Rolo2,3,4
1School of Pharmaceutical Science of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
Toxicology mechanisms and methods
|September 30, 2025
概括
制阻燃剂 (BFRs) 对线粒体有毒,破坏细胞能量生产并引起氧化损伤. 它们的代谢物和替代品带来类似的风险,需要基于机制的安全评估.
科学领域:
- 环境毒理学环境毒理学
- 线粒体生物学 线粒体生物学
- 化学品风险评估 化学品风险评估
背景情况:
- 制阻燃剂 (BFR) 是消费品中广泛存在的环境污染物.
- BFR与不良健康影响有关,但其分子毒性机制尚未完全理解.
- 线粒体越来越被认为是BFR诱导的细胞损伤的关键目标.
研究的目的:
- 审查和整合关于线粒体在BFR毒性中的作用的证据.
- 阐明BFRs引起细胞损伤的分子途径.
- 强调需要基于机制的化学安全风险评估.
主要方法:
- 关于BFR和线粒体毒性的科学证据的文献综述.
- 分析由BFRs引起的线粒体损伤的常见机制.
- 检查BFR生物转化和特定化合物的毒性 (例如,Tetrabromobisphenol A,BDE-209).
主要成果:
- BFRs通过破坏电子运输链和氧化酸化来损害线粒体的生物能量,导致ATP耗尽和线粒体膜潜力的丧失.
- 通过增加反应性氧物种 (ROS) 生产,BFRs诱导氧化应激.
- 像Tetrabromobisphenol A这样的特定BFRs可以触发各种细胞死亡途径 (亡,亡,铁亡),它们的代谢物可能比原始化合物更有毒.
结论:
- 线粒体功能障碍是BFR毒性的核心机制.
- 将BDE-209替换为甲甲乙表明了风险评估的失败,因为替代品具有类似的线粒毒性质.
- 转向基于机制的风险评估的模式转变对于防止开发和使用危险化学品替代品以及设计更安全的替代品至关重要.
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