实验室内恩雅丁B1的肝脏清除:跨物种和细胞模型比较
M Mahdjoub1, E Dubreil2, C Gendre2
1Fougères Laboratory, ANSES French Agency for Food, Environmental and Occupational Health and Safety, Fougères - Rennes, France. mariam.mahdjoub@anses.fr.
在老鼠中,恩雅丁B1 (EnnB1) 菌毒素的清除速度比人类更快. 传统的枯竭试验准确地确定了EnnB1的肝清除率 (ClH),这对于风险评估至关重要.
科学领域:
- 毒理学 毒理学 毒理学
- 药理动力学 药理动力学
- 菌毒素研究 菌毒素研究
背景情况:
- 恩雅丁B1 (EnnB1) 是一种在谷物中发现的Fusarium真菌毒素,对人类造成暴露风险.
- EnnB1是一种新兴的真菌毒素,有有限的毒动力学和毒动力学数据,需要监管评估.
研究的目的:
- 通过使用母化合物耗尽来确定EnnB1的体外肝清除 (ClH).
- 为了比较不同物种 (老鼠,人类),细胞类型 (初级肝细胞,HepaRG) 和模型 (2D,3D) 的EnnB1肝清除.
主要方法:
- 使用常规和介质损失的体外试验分析,主要使用老鼠和人类肝细胞,以及HepaRG细胞 (2D和3D).
- 计算在体外肝脏内在清除值,并推算为体内肝脏清除值 (ClH).
主要成果:
- 肝脏清除 (ClH) 在大鼠 (3.4 L/h/kg) 中明显快于人类 (1 L/h/kg).
- 在初级人类肝细胞和HepaRG 2D细胞之间,ClH是可比的;HepaRG 3D显示较慢的ClH (0.58 L/h/kg).
- 传统的枯竭试验被证明适用于EnnB1 ClH的确定,媒体损失试验显示了初始的快速吸收.
结论:
- 聚合的原发性肝细胞提供可靠的ClH数据,解释了个体间的变异性,这对于生理学基础的药理动力学建模至关重要.
- 这些发现为了解EnnB1毒动学提供了关键数据,并为该新兴菌毒素的监管风险评估提供了信息.
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