Nanosilver inhibition of human P450-selective monooxygenase activities
Human liver microsomes, with relatively high activity for the P450-selective substrates, were incubated at 0.5 mg protein/ml and a range (0–70 μM) of nanosilver concentrations. IC50 values were determined by interpolation in three independent experiments with each data point derived from duplicate incubations. IC50 values are given as means ± S.E.M. (n = 3). P450 concentrations in the assays were derived from data provided by the microsome supplier.
| P450 (P450-Selective) Reaction | Human Liver Microsomes | [P450] in Assayc | [Substrate] in Assay | Nanosilver IC50 |
|---|---|---|---|---|
| μM | ||||
| 7-Methoxyresorufin O-demethylation (CYP1A2) | Celsis F008085-CST | 0.283 | 0.5 | 24.4 ± 1.1 |
| Coumarin 7-hydroxylation (CYP2A6) | Celsis X008064-LSL | 0.202 | 2.5 | 33.5 ± 2.3 |
| 7-EFCa O-deethylation (CYP2B6) | Celsis M008085-JTA | 0.279 | 6.25 | 31.9 ± 2.5 |
| Diclofenac 4-hydroxylation (CYP2C9) | Human Biologics Inc. 112 | 0.235 | 50 | 9.3 ± 0.2 |
| S-Mephenytoin 4-hydroxylation (CYP2C19) | Puracyp 011 | 0.138 | 50 | 6.4 ± 0.1 |
| 7-MAMCb O-demethylation (CYP2D6) | Celsis M008085-JTA | 0.279 | 25 | 21.2 ± 1.3 |
| Chlorzoxazone 6-hydroxylation (CYP2E1) | Human Biologics Inc. 227 | 0.190 | 100 | 16.0 ± 1.4 |
| Testosterone 6β-hydroxylation (CYP3A4) | Human Biologics Inc. 501 | Not supplied | 50 | 8.0 ± 0.3 |
| 7-Benzyloxyquinoline O-debenzylation (CYP3A4) | Human Biologics Inc. 501 | Not supplied | 80 | 8.8 ± 0.5 |