Effect of cannabidiol and hemp extract on viability and function of hepatocytes derived from human induced pluripotent stem cells

IF 2.6 3区医学 Q3 TOXICOLOGY Toxicology in Vitro Pub Date : 2024-09-02 DOI:10.1016/j.tiv.2024.105933

Kayla Campasino, Miranda R. Yourick, Yang Zhao, Estatira Sepehr, Cory Vaught, Jeffrey J. Yourick, Robert L. Sprando, Xiugong Gao

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Abstract

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.

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大麻二酚和大麻提取物对人类诱导多能干细胞肝细胞活力和功能的影响。

自《2018 年农业改进法案》（2018 Farm Bill）通过以来，消费者可获得的含有大麻衍生化合物的产品数量迅速增加。人们已经观察到，食用含有大麻二酚（CBD）的产品（包括大麻提取物）可能会对肝功能产生影响，但这种影响的机制尚不完全清楚。在这项研究中，研究人员利用从人类诱导多能干细胞（iPSCs）中提取的肝细胞来评估 CBD 和大麻提取物在 0.1 至 30 μM 暴露浓度范围内对肝脏的潜在影响。尽管只有在 30 μM 组中，CBD 和大麻提取物才会显著降低细胞活力，但在 0.1-3 μM 的浓度范围内，CBD 和大麻提取物的细胞色素 P450 活性、线粒体膜电位和脂质积累都发生了显著变化。在 3-30 μM 的浓度范围内，CBD 或大麻提取物对白蛋白和尿素的产生、caspase 3/7 活性和细胞内谷胱甘肽有显著影响。这些发现表明，CBD 和大麻提取物可改变肝功能和新陈代谢。本研究提供的数据有助于为评估含有大麻衍生化合物的产品的潜在肝毒性效应提供信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.