Incubations of CLZ with human liver microsomes HL112: evidence for FMO involvement in CLZ N-oxide formation
| CLZ | Incubation Conditions | CLZ N-oxidation | CLZ N-demethylation |
|---|---|---|---|
| μM | pmol/mg protein/min1-a | pmol/mg protein/min1-a | |
| 750 | Control | 368.1 | 138.7 |
| 750 | Heat with NADPH1-b | 369.2 (100.3) | 136.9 (98.7) |
| 750 | Heat without NADPH1-b | 62.7 (17.0) | 83.5 (60.2) |
| 5001-c | Control | 242.6 | 119.4 |
| 500 | +Methimazole (10 μM) | 197.1 (81.2) | 112.7 (94.4) |
| 500 | +Methimazole (25 μM) | 163.1 (67.2) | 110.0 (92.1) |
| 500 | +Methimazole (50 μM) | 142.7 (58.8) | 107.3 (89.9) |
| 500 | +Methimazole (100 μM) | 120.8 (49.8) | 97.3 (81.5) |
| 500 | +Methimazole (150 μM) | 105.9 (43.7) | 94.5 (79.1) |
↵1-a Incubations were conducted in quadruplicate for the heat inactivation experiment and in duplicate for the methimazole inhibition experiments. Each value represents the mean of these determinations. In parentheses is the percentage of control.
↵1-b Microsomal protein was preincubated with CLZ for 5 min at 45°C in the presence and absence of NADPH, cooled on ice for 2 min, and followed by a normal assay procedure.
↵1-c Comparable data at 100 and 350 μM CLZ are not shown.