在培养鱼肝细胞中,物理化学多样化药物的代谢清除
Chrisna Matthee1, A Ross Brown1, Anke Lange1
1Biosciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
Environmental toxicology and chemistry
|July 27, 2025
概括
鱼类肝细胞有效清除活性药物成分 (API),清除率与人类相似. 然而,基因表达和酶活性显示出特定物种的差异,突出显示了需要在水生环境中仔细评估风险的必要性.
科学领域:
- 生态毒理学 生态毒理学
- 环境化学环境化学
- 在体外毒理学.
背景情况:
- 鱼类容易受到制药污染物的影响,影响水生生态系统.
- 了解鱼类中的活性药物成分 (API) 代谢和运输对于环境风险评估至关重要.
- 像初级肝细胞这样的体外模型可以减少生态毒理学中的动物试验.
研究的目的:
- 评估彩虹鱼 (Oncorhynchus mykiss) 主性肝细胞中五种不同的API的肝清除.
- 研究这些API对关键药物代谢和运输基因和酶活性的影响.
- 将鱼类肝细胞数据与人类数据进行比较,以改善风险评估.
主要方法:
- 使用彩虹鱼初级肝细胞单层模型.
- 评估了propranolol,奎蒂亚平,美可芬酸,克洛扎平和olaparib的肝脏清除.
- 分析了基因转录 (abcb1,mrp2,cyp1a,cyp3a) 和细胞染色体P4501A的活动.
主要成果:
- 彩虹鱼肝细胞清除了所有测试的API,清除率与大多数人的清除率相当.
- 与人类数据相比,API暴露显示了基因表达和酶活性的相似性和差异.
- 该研究表明,物种在新陈代谢和运输系统中的特定反应.
结论:
- 彩虹鱼肝细胞模型是用于API危害识别的有用和可重复的工具.
- 从鱼类对人类的API清除和影响的直接推断并不总是有效的.
- 数据支持使用该模型来构建水生环境中API的风险概况.
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