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• W4313891864 endingPage "621" @default.
• W4313891864 startingPage "621" @default.
• W4313891864 abstract "Emerging advances in the field of in vitro toxicity testing attempt to meet the need for reliable human-based safety assessment in drug development. Intrahepatic cholangiocyte organoids (ICOs) are described as a donor-derived in vitro model for disease modelling and regenerative medicine. Here, we explored the potential of hepatocyte-like ICOs (HL-ICOs) in in vitro toxicity testing by exploring the expression and activity of genes involved in drug metabolism, a key determinant in drug-induced toxicity, and the exposure of HL-ICOs to well-known hepatotoxicants. The current state of drug metabolism in HL-ICOs showed levels comparable to those of PHHs and HepaRGs for CYP3A4; however, other enzymes, such as CYP2B6 and CYP2D6, were expressed at lower levels. Additionally, EC50 values were determined in HL-ICOs for acetaminophen (24.0−26.8 mM), diclofenac (475.5−>500 µM), perhexiline (9.7−>31.5 µM), troglitazone (23.1−90.8 µM), and valproic acid (>10 mM). Exposure to the hepatotoxicants showed EC50s in HL-ICOs comparable to those in PHHs and HepaRGs; however, for acetaminophen exposure, HL-ICOs were less sensitive. Further elucidation of enzyme and transporter activity in drug metabolism in HL-ICOs and exposure to a more extensive compound set are needed to accurately define the potential of HL-ICOs in in vitro toxicity testing." @default.
• W4313891864 created "2023-01-10" @default.
• W4313891864 creator A5005270865 @default.
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• W4313891864 date "2023-01-07" @default.
• W4313891864 modified "2023-10-06" @default.
• W4313891864 title "Drug Metabolism of Hepatocyte-like Organoids and Their Applicability in In Vitro Toxicity Testing" @default.
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• W4313891864 doi "https://doi.org/10.3390/molecules28020621" @default.
• W4313891864 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36677681" @default.
• W4313891864 hasPublicationYear "2023" @default.
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