CYP450-Dependent Metabolism and Hepatotoxicity in MPCCs
(A) Schematic representation of APAP metabolism and toxicity.
(B and C) Secreted albumin levels in MPCCs exposed for 24 h to APAP alone (B) or in combination with 200 μM BSO (C) on day 6 post-transfection. Values (mean ± SEM) were normalized to drug-free control wells on each condition (CYP2E1 siRNA, n = 2; CYP3A4 siRNA, n = 5; control siRNA, n = 5; control siRNA + BSO, n = 2; CYP3A4 siRNA + BSO, n = 2). See Figure S1C for CYP2E1 knockdown efficiency.
(D and E) Schematic of atorvastatin metabolism (D) and albumin levels in MPCCs exposed for 24 h to atorvastatin on day 6 post-transfection (E). Normalized data represent mean ± SEM (n = 2).
(F) Summary of IC50 values (mean ± SD) for APAP (left) and atorvastatin (right) in the various conditions. IC50 was calculated using non-linear regression variable slope (normalized) analysis.