The effect of selective P450 and alcohol dehydrogenase inhibitors on 4-oxo-atRA or 4-OH-atRA formation from atRA and formation of 4-oxo-atRA from 4-OH-atRA in HepG2 cells
Data are presented as the percentage of control (mean ± S.D.) unless otherwise indicated. The inhibitors used were 4-methylpyrazole (250 µM, alcohol dehydrogenases), cimetidine (250 µM, alcohol dehydrogenases), ketoconazole (10 µM, P450s), talarozole (1µM, CYP26), testosterone (25 µM, aldo-keto reductases), or carbenoxolone (25 and 50 µM, retinol dehydrogenases). Significant changes in comparison with no inhibitor controls were performed using the unpaired t test.
| Treatment | 4-oxo-atRA Formation | 4-OH-atRA Concentration |
|---|---|---|
| atRA (control) | 100 ± 3 | 100 ± 7 |
| atRA + 4-methylpyrazole | 109 ± 8 | 122 ± 11 |
| atRA+ cimetidine | 130 ± 6* | 149 ± 5* |
| atRA+ ketoconazole (10 µM) | 20 ± 1* | 16 ± 6* |
| atRA+ testosterone | 109 ± 6 | 133 ± 4* |
| atRA + carbenoxolone (25 µM) | 74 ± 3* | 92 ± 22 |
| atRA + carbenoxolone (50 µM) | 80 ± 8* | 99 ± 25 |
| atRA + talarozole (1 µM) | 20 ± 3* | 0 |
| 4-OH-atRA (control) | 100 ± 6 | 100 ± 6 |
| 4-OH-atRA + 4-methylpyrazole | 121 ± 12 | 96 ± 3 |
| 4-OH-atRA + cimetidine | 121 ± 3* | 99 ± 2 |
| 4-OH-atRA + ketoconazole | 110 ± 0 | 75 ± 0* |
| 4-OH-atRA + testosterone | 107 ± 1 | 107 ± 0 |
| 4-OH-atRA + carbenoxolone (25 µM) | 115 ± 9 | 80 ± 9* |
| 4-OH-atRA + carbenoxolone (50 µM) | 117 ± 6* | 96 ± 3 |
↵* P < 0.05.