Figure 5.
Drug metabolic capabilities of induced phenotypes. (A) Differential expression of drug metabolism-related genes in induced phenotypes as fold change versus control groups. (B) sPLS-DA principal component analysis of drug metabolism-related phenotypes. (C) Summary of relevant gene expression for APAP drug metabolism and transport. Quantification of related co-factors shown in terms of intracellular concentration of UDP-glucuronate for UGT1A1-mediated glucuronidation. ATP-availability required for ATP-dependent drug efflux and as a precursor for SULT1A1-related drug detoxification. Intracellular availability of reduced glutathione required for detoxification of monooxygenase-derived drug intermediates in (D) untreated and (E) 20 mM APAP treated groups. (F) Quantification of cytotoxicity after drug exposure compared to control groups. (G) Cellular morphology of hepatocyte sandwich cultures after exposure to 20 mM Acetaminophen (APAP) for 5 h on day 5 (scale bar = 100 μm). Arrowheads show pathological expansion of bile canaliculi.
