在人体体体外细胞模型中,双相似物引起的毒性机制
Rafia Afroze Rifa1, Macarena Gisele Rojo1, Ramon Lavado1
1Department of Environmental Science, Baylor University, Waco, TX, 76798, USA.
Chemico-biological interactions
|March 14, 2025
概括
作为BPA替代品使用的双相似物会诱导人类细胞中的氧化应激和线粒体损伤. 某些类似物,如双AF,AP和P是最强的,表现出与健康风险评估相关的细胞特异性毒性.
科学领域:
- 环境毒理学环境毒理学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 双相似物是BPA的替代品,但它们的安全性值得怀疑.
- 以前的研究表明细胞毒性;本研究研究了特定的毒性机制.
- 双相似物与炎症和慢性疾病有关.
研究的目的:
- 在人类体外细胞模型中研究双相似物 (AF,AP,E,P) 的毒性机制.
- 评估对活性氧物种 (ROS),线粒体膜潜力 (ΔΨm) 和线粒体的影响.
- 为了确定类比特异性和细胞特异性毒理反应.
主要方法:
- 使用的人体体细胞模型:HepaRG,Caco-2,HMC3和HMEC-1.
- 评估的细胞压力标志物:ROS产量,线粒体膜潜力 (ΔΨm) 和线粒体水平.
- 评估了双相似物剂的剂量依赖作用.
主要成果:
- 双类药物诱导了剂量依赖氧化应激 (ROS) 的增加和线粒体膜潜能 (ΔΨm) 的降低.
- 可可-2细胞 (肠细胞) 显示出最高的敏感性,表明组织特异性的脆弱性.
- 双AF,AP和P是ROS和线粒体功能障碍最强的诱导剂.
结论:
- 双相似物具有显著的毒性,影响细胞氧化应激和线粒体完整性.
- 反应是模拟特异性和细胞特异性,肠细胞是特别脆弱的.
- 这些发现对于制定针对双相似物暴露风险的监管策略至关重要.
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