TBE-31 does not improve NASH histology in livers of HFFr-fed Nrf2-/-mice. After sacrifice, livers from Nrf2+/+ and Nrf2-/- mice in Study 2 were removed and fixed in formalin (n = 6–8 mice per group). (A) Representative images for H&E staining of mouse liver sections after 16 weeks RC- or HFFr-feeding, including treatment with DMSO during Weeks 11–16 (scale bars = 100 µm). (B) Representative images for H&E staining of liver sections from Nrf2+/+ and Nrf2-/- mice after 16 weeks RC- or HFFr-feeding including treatment with DMSO or TBE-31 during Weeks 11–16 (scale bars = 100 µm). (C) The extent of disease was assessed using the NAFLD activity score method.39 (D) Representative images for van Gieson staining of liver sections from Nrf2+/+ and Nrf2-/- mice after 16 weeks of HFFr-feeding and treatment with DMSO or TBE-31. White bars, DMSO-treated; black bars, TBE-31 treated (6–8 mice per group). Results are means ± SEM. Significant increases in NAFLD activity score, relative to that in livers from RC-fed DMSO-treated Nrf2+/+ mice, are indicated by: ***P < .001. The significant decrease in NAFLD activity score resulting from treatment with TBE-31, relative to HFFr-fed DMSO-treated Nrf2+/+ mice, is denoted by: $P < .05.