Table 2.
Hepatic gene expression of antioxidant enzymes and ABC efflux transporters after a 4 day treatment with vehicle (corn oil) or LCA in mice
| Corn oil vehicle | LCA | |||||
|---|---|---|---|---|---|---|
| Nrf2+/+ | Nrf2−/− | P-valuea | Nrf2+/+ | Nrf2−/− | P-valuea | |
| Antioxidant enzymes | ||||||
| Gclm | 1.00 ± 0.05 | 0.82 ± 0.06 | 0.024 | 1.96 ± 0.12 | 1.53 ± 0.10 | 0.016 |
| Gclc | 1.00 ± 0.08 | 0.55 ± 0.04 | <0.001 | 2.03 ± 0.13 | 1.07 ± 0.10 | <0.001 |
| Trx1 | 1.00 ± 0.05 | 1.09 ± 0.11 | 0.509 | 3.74 ± 0.57 | 1.39 ± 0.14 | <0.001 |
| Nqo1 | 1.00 ± 0.06 | 0.28 ± 0.06 | <0.001 | 2.83 ± 0.43 | 0.48 ± 0.08 | <0.001 |
| Ho1 | 1.00 ± 0.09 | 0.79 ± 0.06 | 0.007 | 3.35 ± 0.37 | 1.10 ± 0.15 | <0.001 |
| Gsta1/2 | 1.00 ± 0.11 | 0.45 ± 0.05 | <0.001 | 8.56 ± 1.44 | 0.70 ± 0.11 | <0.001 |
| Gsta4 | 1.00 ± 0.05 | 0.69 ± 0.04 | <0.001 | 2.65 ± 0.36 | 1.16 ± 0.10 | <0.001 |
| Gstm1 | 1.00 ± 0.05 | 0.37 ± 0.03 | <0.001 | 1.72 ± 0.07 | 0.57 ± 0.03 | <0.001 |
| Gstp1 | 1.00 ± 0.06 | 0.89 ± 0.08 | 0.239 | 1.15 ± 0.23 | 1.24 ± 0.18 | 0.157 |
| Transporters | ||||||
| Abcc1 (Mrp1) | 1.00 ± 0.05 | 1.02 ± 0.10 | 0.946 | 2.70 ± 0.31 | 1.54 ± 0.10 | 0.002 |
| Abcc2 (Mrp2) | 1.00 ± 0.03 | 0.96 ± 0.05 | 0.474 | 1.35 ± 0.09 | 0.89 ± 0.10 | 0.005 |
| Abcc3 (Mrp3) | 1.00 ± 0.07 | 0.17 ± 0.03 | <0.001 | 1.92 ± 0.16 | 0.33 ± 0.05 | <0.001 |
| Abcc4 (Mrp4) | 1.00 ± 0.08 | 0.55 ± 0.06 | <0.001 | 2.79 ± 0.27 | 0.82 ± 0.16 | <0.001 |
| Abcc5 (Mrp5) | 1.00 ± 0.05 | 0.99 ± 0.09 | 0.921 | 2.23 ± 0.34 | 0.97 ± 0.07 | 0.007 |
| Abcb1a (Mdr1a) | 1.00 ± 0.05 | 0.66 ± 0.12 | 0.004 | 14.45 ± 5.19 | 2.09 ± 0.74 | 0.017 |
| Abcb1b (Mdr1b) | 1.00 ± 0.07 | 1.14 ± 0.15 | 0.389 | 12.04 ± 6.65 | 1.60 ± 0.39 | 0.069 |
| Abcg2 (Bcrp1) | 1.00 ± 0.05 | 0.78 ± 0.09 | 0.032 | 1.47 ± 0.12 | 1.02 ± 0.10 | 0.013 |
| Abcb11 (Bsep1) | 1.00 ± 0.06 | 1.73 ± 0.08 | 0.005 | 2.13 ± 0.36 | 2.73 ± 0.22 | 0.059 |
| Ntcp | 1.00 ± 0.10 | 0.71 ± 0.05 | <0.001 | 0.56 ± 0.03 | 0.50 ± 0.03 | 0.064 |
Expression levels of each gene were standardized to mean mRNA levels in corn oil-treated Nrf2+/+ mice. LCA treatment (125 mg·kg−1 body wt.): LCA was administered twice daily for 4 days. Mean ± SEM (n = 8–12).
Pair-wise comparison between the genotypes within the respective treatment. Note that all genes within the Nrf2+/+ mice group are significantly different between corn oil and LCA except for Gstp1.
Abc, ATP-binding cassette; Gclc, glutamate cysteine ligase catalytic subunit; Gclm, glutamate cysteine ligase modulatory subunit; Ho1, haeme oxygenase-1; LCA, lithocholic acid; Mdr1, multidrug resistance protein 1; Mrp, multidrug resistance-associated protein; Nrf2, nuclear factor (erythroid 2-related) factor 2; Trx1, thioredoxin reductase 1.