Table 3.
Histological Examination Reveals That TBE-31 Does not Decrease the Severity of Liver Fibrosis in Nrf2-null Mice Fed a HFFr Diet
| Parameter | Value (n) |
|||
|---|---|---|---|---|
|
Nrf2+/+ mice |
Nrf2-/- mice |
|||
| DMSO | TBE-31 | DMSO | TBE-31 | |
| NASa (maximum 8) | ||||
| RC | 0.375 (8) | 0.125 (8) | 0.5 (6) | 1.0 (7) |
| HFFr | 2.125 (8) | 1.0 (9) | 3.167 (6) | 2.8 (5) |
| Steatosis component of NASb (0–3) | ||||
| RC | 0.125 (8) | 0 (8) | 0.1667 (6) | 0.1429 (7) |
| HFFr | 1.375 (8) | 0.5556 (9) | 1.833 (6) | 1.8 (5) |
| Inflammatory component of NASc (0–3) | ||||
| RC | 0.25 (8) | 0.125 (8) | 0.3333 (6) | 0.8571 (7) |
| HFFr | 0.75 (8) | 0.4444 (9) | 1.167 (6) | 1 (5) |
| Ballooning component of NASd (0–2) | ||||
| RC | 0 (8) | 0 (8) | 0 (6) | 0 (7) |
| HFFr | 0 (8) | 0 (9) | 0.1667 (6) | 0 (5) |
| Fibrosis stage (0–3)e | ||||
| RC | 0.14 (8) | 0.07 (8) | 0.20 (6) | 0.51 (7) |
| HFFr | 0.33 (8) | 0.10 (9) | 0.75 (6) | 0.69 (5) |
NAS was estimated to be significantly higher in livers of HFFr-fed mice than in livers of RC-fed animals in both genotypes (Kruskal-Wallis test; P < .0001). DMSO-treated Nrf2+/+ mice fed the HFFr diet had a significantly higher NAS than did TBE-31-treated mice on the HFFr diet (Kruskal-Wallis H test; P < .05). NAS estimates in livers of Nrf2-/- animals fed the HFFr diet were higher, but not significantly higher, than those in livers of Nrf2+/+ mice fed the HFFr diet (Kruskal-Wallis test; P > .05).
Livers from mice fed the HFFr diet exhibited more steatosis than their RC-fed counterparts in both genotypes (Kruskal-Wallis H test; P < .0001). However, no significant difference in hepatic steatosis was observed between DMSO- and TBE-31-treated mice fed the same diet.
The hepatic inflammatory component was significantly higher in mice fed the HFFr diet when compared with their RC-fed counterparts (Kruskal-Wallis H test; P < .0001). No significant difference in inflammation was observed between livers from DMSO- and TBE-31-treated mice fed on same diet in both genotypes.
Ballooning was seen only in the liver of 1 Nrf2-/- mouse that was fed the HFFr diet.
Livers from mice fed the HFFr diet showed more fibrosis (this is not included in NAS calculation) when compared with mice fed the RC diet in both genotypes. Nrf2+/+ mice fed the HFFr diet exhibited significantly less hepatic fibrosis when treated with TBE-31 than did Nrf2+/+ mice treated with DMSO (Kruskal-Wallis H test; P < .05). Fibrosis in livers of Nrf2-/- mice fed the HFFr diet was significantly higher than in livers of their wild-type counterparts (Kruskal-Wallis H test; P < .05). TBE-31 treatment had no effect on liver fibrosis in Nrf2-/- mice.