Inhibition by anti-CYP antibodies of the metabolic activation of diclofenac in incubations with rat liver microsomes1-a
| Antibody | IgG | Rat Liver Microsomes | Diclofenac | % Control1-b Total (M1, M3) |
|---|---|---|---|---|
| mg/nmol CYP | μM | |||
| Anti-1A IgG | 5 | Male | 5 | 100 (100, 100) |
| Anti-2B IgG | 5 | Male | 5 | 67 (70, 63) |
| Anti-2C IgG | 5 | Male | 5 | 45 (50, 40) |
| Anti-3A IgG | 5 | Male | 5 | 55 (58, 52) |
| Anti-2B/2C/3A IgG | 2.5 each | Male | 5 | 22 (20, 23) |
| Anti-2C11 IgG | 5 | Male | 5 | 62 (64, 59) |
| Anti-2C7 IgG | 5 | Male | 5 | 46 (47, 45) |
| Anti-1A IgG | 5 | Female | 5 | 100 (100, 100) |
| Anti-2B IgG | 5 | Female | 5 | 47 (47, 48) |
| Anti-2C IgG | 5 | Female | 5 | 50 (55, 45) |
| Anti-3A IgG | 5 | Female | 5 | 58 (59, 57) |
| Anti-2B/2C/3A IgG | 2.5 each | Female | 5 | 30 (30, 31) |
| Anti-2C11 IgG | 5 | Female | 5 | 97 (95, 100) |
| Anti-2C7 IgG | 5 | Female | 5 | 42 (44, 40) |
↵1-a Diclofenac and GSH in phosphate buffer were added to rat liver microsomes suspended in phosphate buffer (0.1 M; pH 7.4) containing EDTA. Each anti-CYP IgG was preincubated with microsomes for 15 min at room temperature. Control incubations contained preimmune IgG. Reactions were initiated by adding NADPH and proceeded for an additional 30 min. The products were analyzed by LC/MS/MS.
↵1-b % Control (total) was calculated based on decreases in the formation of M1 and M3. % Control also was calculated individually for M1 and M3 and the data are presented in parentheses.