ArticleThe AAPS journal2025
In Vitro-In Silico Models to Elucidate Mechanisms of Bile Acid Disposition and Cellular Aerobics in Human Hepatocytes.
Article in The AAPS journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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7 authors.
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Abstract
Understanding the kinetics of hepatic processes, such as bile acid (BA) handling and cellular aerobic metabolism, is crucial for advancing our knowledge of liver toxicity, particularly drug-induced cholestasis (DiCho). This article aimed to construct interpretable models with parameter estimations serving as reference values when investigating these cell metrics. Longitudinal datasets on BA disposition and oxygen consumption rates were collected using sandwich-cultured human hepatocytes. Chenodeoxycholic acid (CDCA), lithocholic acid (LCA), as well as their amidated and sulfate-conjugated metabolites were quantified with liquid chromatography-mass spectrometry. The bile salt export pump (BSEP) abundance was monitored with targeted proteomics and modelled for activity assessment. Oxygen consumption was measured using Seahorse XFp analyser. Ordinary differential equation-based models were solved in R. The basolateral uptake and efflux clearance of glycine-conjugated CDCA (GCDCA) were estimated at 1.22 µL/min/10
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