Optical Isomers of Atorvastatin, Rosuvastatin and Fluvastatin Enantiospecifically Activate Pregnane X Receptor PXR and Induce CYP2A6, CYP2B6 and CYP3A4 in Human Hepatocytes
Fig 5
Effects of statin enantiomers on transcriptional activity of human pregnane X receptor.
LS180 cells, transiently transfected with p3A4-luc reporter, were seeded in 96-well plates and stabilized for 16 h and then incubated for 24 h with enantiopure forms of atorvastatin, rosuvastatin and fluvastatin in concentration ranging from 10−10 M to 10−4 M in the absence (agonist mode–upper line) or presence (antagonist mode–lower line) of rifampicin (RIF; 10 μM). The vehicle was DMSO (0.1% v/v). After the treatments, cells were lysed and luciferase activity was measured. Treatments were performed in triplicates. Data are expressed as a fold induction of luciferase activity over control cells (agonist mode) or as a percentage of maximal activation attained by RIF (antagonist mode). The values of EC50 and IC50 from n independent cell passages were calculated where appropriate and the average values are indicated in plots. Representative gene reporter assays are shown. Student´s t-test, One-way ANOVA followed by Dunnett's post test and EC50/IC50 values were calculated using GraphPad Prism.