Table 4.
Intracellular concentrations of 11 different bile acids (BAs) in PCLS incubated for 48 h in the presence of the humanized BA mixture, and with or without a cholestatic drug: chlorpromazine (CPZ) (30 µM), cyclosporin A (CSA) (6 µM), or glibenclamide (GB) (65 µM). BAs are listed from low to high hydrophobicity
| pmol/mg protein | BA control | CPZ 30 μM | CSA 6 μM | GB 65 μM |
|---|---|---|---|---|
| THDCA | 5.5 ± 0.4 (1.0%) | 9.0 ± 3.0 (0.8%) | 4.4 ± 1.0 (1.4%) | 11.4 ± 2.6 (2.2%) |
| TCA | 177.7 ± 54.8 (33.6%) | 351.2 ± 67.0 (29.8%) | 33.3 ± 2.0 (10.3%)* | 135.2 ± 19.9 (26.4%) |
| TCDCA | 7.2 ± 1.2 (1.4%) | 18.2 ± 5.3 (1.5%) | 3.6 ± 0.4 (1.1%)* | 8.6 ± 1.2 (1.7%) |
| TDCA | 8.2 ± 1.3 (1.6%) | 44.3 ± 5.1 (3.8%)**** | 18.8 ± 2.3 (5.9%)** | 14.6 ± 0.9 (2.9%)** |
| GCA | 20.3 ± 6.8 (3.8%) | 26.1 ± 3.5 (2.2%) | 5.7 ± 1.0 (1.8%) | 22.4 ± 6.1 (4.4%) |
| UDCA | 31.9 ± 3.2 (6.0%) | 46.3 ± 3.0 (3.9%)* | 28.9 ± 1.6 (9.0%) | 24.5 ± 3.9 (4.8%) |
| HDCA | 2.5 ± 1.7 (0.5%) | 13.6 ± 3.9 (1.2%)* | 12.9 ± 1.8 (4.0%)** | 25.7 ± 1.5 (5.0%)**** |
| CA | 206.2 ± 17.6 (39.0%) | 314.1 ± 29.7 (26.7%)* | 78.8 ± 4.9 (24.5%)**** | 132.3 ± 11.3 (25.9%)** |
| CDCA | 16.3 ± 1.8 (3.1%) | 41.3 ± 6.4 (3.55%)** | 19.3 ± 2.6 (6.05%) | 14.8 ± 1.3 (2.9%) |
| DCA | 52.0 ± 7.0 (9.8%) | 297.9 ± 25.1 (25.3%)**** | 106.9 ± 18.8 (33.2%)* | 121.3 ± 8.6 (23.7%)**** |
| LCA | 1.5 ± 0.3 (0.3%) | 14.9 ± 8.6 (1.3%) | 8.9 ± 4.3 (2.8%) | 0.9 ± 0.3 (0.2%) |
| Total | 529.3 ± 82.3 (100%) | 1177.0 ± 113.2 (100%) | 321.7 ± 29.7 (100%) | 511.7 ± 43.6 (100%) |
Data for individual intracellular BA concentrations are expressed as mean ± SEM of five independent experiments (n = 5 mice), with the percentage of the total amount of BA in parentheses
A one-way ANOVA was performed, followed by a Dunnett’s post hoc test to compare data for different drug concentrations with their control (*p < 0.05; **p < 0.01; ***p < 0.001, ****p < 0.0001) (Data for additional drug concentrations can be found in Supplementary Table S4)