Division of Toxicology, Office of Applied Research and Safety Assessment, US FDA/CFSAN, Laurel, MD 20708, USA.
Division of Toxicology, Office of Applied Research and Safety Assessment, US FDA/CFSAN, Laurel, MD 20708, USA.
Toxicol In Vitro. 2024 Dec;101:105933. doi: 10.1016/j.tiv.2024.105933. Epub 2024 Sep 2.
Since the passage of the 2018 Agriculture Improvement Act (2018 Farm Bill), the number of products containing cannabis-derived compounds available to consumers have rapidly increased. Potential effects on liver function as a result from consumption of products containing cannabidiol (CBD), including hemp extracts, have been observed but the mechanisms for the effects are not fully understood. In this study, hepatocytes derived from human induced pluripotent stem cells (iPSCs) were used to evaluate potential hepatic effects of CBD and hemp extract at exposure concentrations ranging from 0.1 to 30 μM. Despite that a significant reduction in cell viability occurred only in the 30 μM group for both CBD and hemp extract, significant changes to cytochrome P450 activity, mitochondrial membrane potential, and lipid accumulation occurred within the concentration range of 0.1-3 μM for both CBD and hemp extract. Albumin and urea production, caspase 3/7 activity, and intracellular glutathione were significantly affected within the concentration range of 3-30 μM by CBD or hemp extract. These findings indicate that CBD and hemp extract can alter hepatic function and metabolism. The current study contributes data to help inform the evaluation of potential hepatotoxic effects of products containing cannabis-derived compounds.
自 2018 年农业改良法案（2018 年农业法案）通过以来，可供消费者使用的含有大麻衍生化合物的产品数量迅速增加。已经观察到消费含有大麻二酚 (CBD) 的产品（包括麻提取物）对肝功能的潜在影响，但作用机制尚不完全清楚。在这项研究中，用人诱导多能干细胞 (iPSC) 衍生的肝细胞来评估 CBD 和麻提取物在 0.1 至 30 μM 的暴露浓度范围内对潜在肝脏的影响。尽管 CBD 和麻提取物在 30 μM 组的细胞活力显著降低，但 CBD 和麻提取物在 0.1-3 μM 的浓度范围内，细胞色素 P450 活性、线粒体膜电位和脂质积累均发生显著变化。CBD 或麻提取物在 3-30 μM 浓度范围内显著影响白蛋白和尿素的产生、半胱天冬酶 3/7 活性和细胞内谷胱甘肽。这些发现表明 CBD 和麻提取物可以改变肝脏功能和代谢。本研究提供的数据有助于评估含大麻衍生化合物产品的潜在肝毒性作用。
