Table 4.
Biochemical and Molecular Evaluation of Oxidative Stress and Liver Inflammation and Necrosis in Wt, Gsta4−/−, Ppara−/−, and Ppara−/−/Gsta4−/− dKO Mice Receiving a Chow or 70% HF Diet
| Group | GSSG/GSH | mRNA expression (fold change) |
||
|---|---|---|---|---|
| Cyp2e1 | Nox2 | Nox4 | ||
| Wt chow | 0.80 ± 0.10 | 1.00 ± 0.12 | 1.00 ± 0.06 | 1.00 ± 0.25 |
| Wt 70% HF | 0.89 ± 0.07 | 1.41 ± 0.13∗ | 1.43 ± 0.09 | 0.78 ± 0.09 |
| Gsta4−/− chow | 0.85 ± 0.17 | 1.24 ± 0.06 | 1.13 ± 0.01 | 1.49 ± 0.34 |
| Gsta4−/− 70% HF | 0.83 ± 0.06 | 1.30 ± 0.09 | 1.34 ± 0.15 | 0.80 ± 0.08 |
| Ppara−/− chow | 0.82 ± 0.10 | 0.86 ± 0.06 | 1.26 ± 0.04 | 1.24 ± 0.30 |
| Ppara−/− 70% HF | 1.79 ± 0.34∗† | 1.34 ± 0.09∗ | 3.68 ± 0.43∗† | 6.57 ± 0.49∗† |
| dKO chow | 0.84 ± 0.11 | 0.97 ± 0.03 | 1.03 ± 0.16 | 0.78 ± 0.18 |
| dKO 70% HF | 3.81 ± 0.79∗‡ | 1.65 ± 0.07∗† | 3.65 ± 0.54∗† | 5.43 ± 0.36∗† |
| P value | ||||
| Genotype | <0.001 | 0.081 | <0.001 | <0.001 |
| Diet | <0.001 | <0.001 | <0.001 | <0.001 |
| Interaction | <0.001 | 0.006 | <0.001 | <0.001 |
Data are expressed as means ± SEM. Hepatic GSSG/GSH ratio was determined as stated in Materials and Methods. Gene expression was assessed by real-time RT-PCR using 2−ΔΔCT method, as described in Materials and Methods. Statistical analysis was performed by two-way analysis of variance, followed by Student-Newman-Keuls post hoc analysis. n = 6 animals per wild-type group; n = 8 animals per knockout group.
∗P < 0.05 for chow versus 70% HF diet (within each genotype).
†P < 0.05 (between genotypes for 70% HF diet).
‡P < 0.01 (between genotypes for 70% HF diet).
dKO, double knockout; GSH, reduced glutathione; GSSG, oxidized glutathione; HF, high fat; Nox, NADPH oxidase; Wt, wild type.