Comparison of Drug Metabolism and Its Related Hepatotoxic Effects in HepaRG, Cryopreserved Human Hepatocytes, and HepG2 Cell Cultures

CYP2B6型 药物代谢 CYP3A4型 肝细胞 细胞培养 化学 细胞色素P450 细胞毒性 体外 生物 生物化学 药理学 遗传学
作者
Yuichi Yokoyama,Yoshifumi Sasaki,Natsuko Terasaki,Taku Kawataki,Koji Takekawa,Yumiko Iwase,Tominaga Shimizu,Seigo Sanoh,Shigeru Ohta
出处
期刊:Biological & Pharmaceutical Bulletin [Pharmaceutical Society of Japan]
卷期号:41 (5): 722-732 被引量:119
标识
DOI:10.1248/bpb.b17-00913
摘要

Differentiated HepaRG cells maintain liver-specific functions such as drug-metabolizing enzymes. In this study, the feasibility of HepaRG cells as a human hepatocyte model for in vitro toxicity assessment was examined using selected hepatotoxic compounds. First, basal drug-metabolizing enzyme activities (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, uridine 5′-diphospho-glucuronosyltransferase [UGT], and sulfotransferases [SULT]) were measured in HepaRG, human hepatocytes, and HepG2 cells. Enzyme activities in differentiated HepaRG cells were comparable to those in human hepatocytes and much higher than those in HepG2 cells, except for SULT activity. Second, we examined the cytotoxicity of hepatotoxic compounds, acetaminophen (APAP), aflatoxin B1 (AFB1), cyclophosphamide (CPA), tamoxifen (TAM), and troglitazone (TGZ) in HepaRG cells and human hepatocytes. AFB1- and CPA-induced cytotoxicities against HepaRG cells were comparable to those against human hepatocytes. Furthermore, the cytotoxicities of these compounds were inhibited by 1-aminobenzotriazole (ABT), a broad CYP inhibitor, in both cells and were likely mediated by metabolic activation by CYP. Finally, toxicogenomics analysis of HepG2 and HepaRG cells after exposure to AFB1 and CPA revealed that numerous p53-related genes were upregulated- and the expression of these genes was greater in HepaRG than in HepG2 cells. These results suggest that gene expression profiles of HepaRG cells were affected more considerably by the toxic mechanisms of AFB1 and CPA than the profiles of HepG2 cells were. Therefore, our investigation shows that HepaRG cells could be useful human hepatic cellular models for toxicity studies.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
桐桐应助暴躁小龙采纳,获得10
3秒前
7秒前
8秒前
蓬松小面包完成签到 ,获得积分20
9秒前
bkagyin应助大白采纳,获得10
9秒前
9秒前
量子星尘发布了新的文献求助10
10秒前
收集快乐发布了新的文献求助10
11秒前
bsf123完成签到,获得积分10
11秒前
12秒前
DeepLearning发布了新的文献求助10
14秒前
14秒前
科研通AI2S应助细辛采纳,获得10
14秒前
15秒前
15秒前
俭朴依白完成签到,获得积分10
15秒前
ElbingX完成签到,获得积分10
17秒前
暴躁小龙发布了新的文献求助10
18秒前
文档发布了新的文献求助10
19秒前
19秒前
严溯发布了新的文献求助10
20秒前
20秒前
22秒前
momo发布了新的文献求助10
22秒前
不可思宇完成签到,获得积分10
23秒前
23秒前
浩浩发布了新的文献求助10
24秒前
Philip发布了新的文献求助10
25秒前
26秒前
赘婿应助SherlockHe采纳,获得10
26秒前
橘子的角动量完成签到,获得积分10
27秒前
严溯完成签到,获得积分10
28秒前
29秒前
胡航航发布了新的文献求助20
29秒前
雨的痕迹发布了新的文献求助10
30秒前
AnnieSsy完成签到,获得积分10
30秒前
程程发布了新的文献求助10
31秒前
浩浩完成签到,获得积分10
32秒前
朴素的小霸王完成签到 ,获得积分10
34秒前
RESLR发布了新的文献求助20
36秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989297
求助须知:如何正确求助?哪些是违规求助? 3531418
关于积分的说明 11253893
捐赠科研通 3270097
什么是DOI,文献DOI怎么找? 1804884
邀请新用户注册赠送积分活动 882087
科研通“疑难数据库(出版商)”最低求助积分说明 809158