大麻和大麻提取物对来自人类诱导多能干细胞的肝细胞的活力和功能的影响
Kayla Campasino1, Miranda R Yourick1, Yang Zhao1
1Division of Toxicology, Office of Applied Research and Safety Assessment, US FDA/CFSAN, Laurel, MD 20708, USA.
概括
Cannabidiol (CBD) 和大麻提取物即使在低剂量也可能影响肝功能. 这项研究使用人肝细胞来表明,这些大麻化合物改变了关键的代谢过程,可能会影响肝脏健康.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 药理学 药理学是指药理学的学科.
- 毒理学 毒理学 毒理学
背景情况:
- 2018年农业法案使大麻合法化,增加了消费者获得大麻衍生产品的机会,如大麻二醇 (CBD).
- 从CBD和大麻提取物消费中观察到对肝功能的影响,需要进一步调查潜在机制.
- 了解这些广泛使用的产品的潜在肝毒性至关重要.
研究的目的:
- 为了研究大麻二醇 (CBD) 和大麻提取物的潜在肝脏影响.
- 为了评估不同暴露度的肝细胞功能和新陈代谢的变化.
- 为评估大麻制品的安全性提供数据.
主要方法:
- 使用的肝细胞来源于人类诱导的多能干细胞 (iPSCs).
- 暴露于CBD和大麻提取物的细胞度在0.1至30μM之间.
- 评估了细胞活力,细胞染色体P450活性,线粒体膜潜力,脂质积累,白蛋白和尿素生产,酶3/7活性和细胞内谷氨水平.
主要成果:
- 细胞染色体P450活性,线粒体膜潜力和脂质积累的显著变化发生在0.1-3μM.
- 专和尿素的产生,酶3/7活性和细胞内谷氨受到了3-30μM的影响.
- 只有在最高度 (30微米) 时才观察到细胞活力下降.
结论:
- CBD和大麻提取物可以显著改变肝功能和新陈代谢.
- 这些影响发生在与消费者产品暴露相关的度范围内.
- 该研究为评估与大麻衍生化合物相关的潜在肝毒性风险提供了必要的数据.
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