Regular ArticleEvaluation of Human Hepatocytes Cultured by Three-dimensional Spheroid Systems for Drug Metabolism
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Liver three-dimensional cellular models for high-throughput chemical testing
2023, Cell Reports MethodsExpression and functional activity of cytochrome P450 enzymes in human hepatocytes with sustainable reproducibility for in vitro phenotyping studies
2022, Advances in PharmacologyCitation Excerpt :Interestingly, this metabolite was detected in plasma of baboons, but not mice, rats, or marmosets (Faigle et al., 1988, unpublish data). Production of 3′-hydroxy-4′-methoxydiclofenac was not detected neither in human hepatocyte suspensions (cell concentration: ∼ 750,000 cells/mL; incubation time: 2 h), human hepatocytes cultured in three-dimensional spheroid system (2.0 × 104 cells/well on 96 format Cell-able; Incubation time, 7 days), S-9 fractions (protein concentration, 1 mg/mL; incubation time, 2 h), nor in human liver microsomes (protein concentration: 2 mg/mL; incubation time: 2 h) incubated with 10 μM diclofenac (Dalvie et al., 2009; Ohkura et al., 2014). Detection of 3′-hydroxy-4′-methoxydiclofenac in hepatocytes and S9 fractions might depend on the differences of the enzyme assay conditions, the lot-to-lot differences of enzyme sources, or the sensitivity of quantification methods.
Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction
2021, Acta Pharmaceutica Sinica BIntegration of in vitro data from three dimensionally cultured HepaRG cells and physiologically based pharmacokinetic modeling for assessment of acetaminophen hepatotoxicity
2020, Regulatory Toxicology and PharmacologyCitation Excerpt :Likewise, the activity of CYP1A2 was also higher in 3D than 2D HepaRG cultures and its expression levels can be more effectively induced by drugs such as omeprazole in 3D cultures (Ramaiahgari et al., 2017). It was even showed that CYP1A2 mRNA levels were several fold higher in human hepatocyte spheroids cultured for 2–7 days than in the cryopreserved primary human hepatocytes (Ohkura et al., 2014). Therefore, although CYP2E1 and 1A2 expression and activities were not directly measured in HepaRG cells in the current study, their levels, as demonstrated by others above, are likely higher in the 3D cultures, which may contribute to higher NAPQI levels and the observed higher sensitivity of the 3D cells to APAP.