title: Study Liver Cytochrome P450 3A4 Inhibition and Hepatotoxicity Using DMSO-Differentiated HuH-7 Cells.
abstract: Metabolically competent, inexpensive, and robust in vitro cell models are needed for studying liver drug-metabolizing enzymes and hepatotoxicity. Human hepatoma HuH-7 cells develop into a differentiated in vitro model resembling primary human hepatocytes after a 2-week dimethyl sulfoxide (DMSO) treatment. DMSO-treated HuH-7 cells express elevated cytochrome P450 3A4 (CYP3A4) enzyme gene expression and activity compared to untreated HuH-7 cells. This cell model could be used to study CYP3A4 inhibition by reversible and time-dependent inhibitors, including drugs, food-related substances, and environmental chemicals. The DMSO-treated HuH-7 model is also a suitable tool for investigating hepatotoxicity. This chapter describes a detailed methodology for developing DMSO-treated HuH-7 cells, which are subsequently used for CYP3A4 inhibition and hepatotoxicity studies.
authors: Division of Applied Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, 8301 Muirkirk Road, Laurel, MD, 20708, USA. yitong.liu@fda.hhs.gov.
authors: Yitong
authors: Y
authors: Liu
mesh_terms: D045744:Cell Line, Tumor; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D057166:High-Throughput Screening Assays; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D008954:Models, Biological; D015262:Xenobiotics / Q000494:pharmacology*
chemical_list: D015262:Xenobiotics; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D004121:Dimethyl Sulfoxide
keywords: CYP3A4; DMSO; Hepatotoxicity; HuH-7; Inhibition