Table 3.
Extra-hepatic microsome activities for cyp2b (bupropion), cyp2c (tolbutamide and repaglinide), cyp2d (bufuralol), cyp2e (chlorzoxazone), cyp2j (ebastine), cyp3a (midazolam) and cyp4a (dodecanoic acid) in C57BL6 mice fed a normal diet (ND) or a HFD (LDR, low-diet responders; and HDR, high-diet responders after an eight-week period): (A) renal microsomes; (B) lung microsomes; and (C) heart microsomes.
| (A) | |||
| Kidney | ND | LDR | HDR |
| (pmol/mg protein/min) | |||
| Bupropion → Hydroxybupropion | 12.5 ± 0.6 | 12.6 ± 0.4 | 8 ± 1 ** |
| Tolbutamide → Hydroxytolbutamide | 1.76 ± 0.06 | 2.63 ± 0.01 ᵵ | 2.10 ± 0.04 ** |
| Repaglinide → M1-repaglinide | 0.09 ± 0.01 | 0.105 ± 0.002 | 0.073 ± 0.003 |
| Bufuralol → Hydroxybufuralol | 3.50 ± 0.03 | 7.7 ± 0.4 ᵵ | 7.4 ± 0.2 ᵵ |
| Chlorzoxazone → Hydroxychlorzoxazone | 130 ± 6 | 144.6 ± 0.2 ** | 108 ± 3 ** |
| Ebastine → Hydroxyebastine and carebastine | 13 ± 1 | 13.9 ± 0.3 | 9 ± 1 * |
| Midazolam → 1′-hydroxymidazolam | 0.24 ± 0.02 | 0.065 ± 0.002 ᵵ | 0.047 ± 0.008 ᵵ |
| Dodecanoic acid → 12-hydroxydecanoic acid | 173 ± 27 | 193 ± 3 | 118 ± 24 * |
| (B) | |||
| Lung | ND | LDR | HDR |
| (pmol/mg protein/min) | |||
| Bupropion → Hydroxybupropion | 538 ± 26 | 476 ± 4 * | 467 ± 14 ** |
| Tolbutamide → Hydroxytolbutamide | 0.64 ± 0.02 | 0.59 ± 0.03 | 0.54 ± 0.01 ** |
| Repaglinide → M1-repaglinide | N/F | N/F | N/F |
| Bufuralol → Hydroxybufuralol | 0.59 ± 0.02 | 0.55 ± 0.02 * | 0.425 ± 0.001 ᵵ |
| Chlorzoxazone → Hydroxychlorzoxazone | 477 ± 16 | 629 ± 79 ** | 535 ± 19 |
| Ebastine → Hydroxyebastine and carebastine | 17 ± 1 | 12.6 ± 0.9 * | 7 ± 3 ᵵ |
| Midazolam → 1′-hydroxymidazolam | 0.51 ± 0.01 | 0.47 ± 0.04 | 0.51 ± 0.01 |
| Dodecanoic acid → 12-hydroxydecanoic acid | 93 ± 6 | 78 ± 1 * | 68 ± 4 ᵵ |
| (C) | |||
| Heart | ND | LDR | HDR |
| (pmol/mg protein/min) | |||
| Bupropion → Hydroxybupropion | 0.15 ± 0.01 | 0.037 ± 0.004 ᵵ | 0.025 ± 0.003 ᵵ |
| Tolbutamide → Hydroxytolbutamide | N/F | N/F | N/F |
| Repaglinide → M1-repaglinide | N/A | N/A | N/A |
| Bufuralol → Hydroxybufuralol | N/A | N/A | N/A |
| Chlorzoxazone → Hydroxychlorzoxazone | 1.7 ± 0.1 | 1.2 ± 0.1 * | 1.7 ± 0.2 |
| Ebastine → Hydroxyebastine and carebastine | 0.8 ± 0.1 | 0.76 ± 0.06 | 0.78 ± 0.06 |
| Midazolam → 1′-hydroxymidazolam | N/F | N/F | N/F |
| Dodecanoic acid → 12-hydroxydecanoic acid | N/F | N/F | N/F |
Cyp450 activities determined at 3 km are reported as the rate of metabolite formation in pmol/mg prot/min ± SD (* p < 0.05, ** p < 0.01 and ᵵ p < 0.001 compared to ND). N/F, activity not found; N/A, Not Available (in vitro incubation could not be determined).