Figure 8.

NorUDCA lowers SIRT1 expression leading to restored FXR signaling, improved liver parenchyma status, and reduced apoptosis, ductular reaction, and fibrogenesis after BDL. (A) IHC in liver sections using a SIRT1 Ab and (B) western blotting analysis showing reduction of SIRT1, but (C) sustained FXR protein expression in NorUDCA/SIRT^oe mice after BDL. (D) H&E staining of liver sections, (E) quantification of caspase‐3 activity on liver protein lysates, and (F) TUNEL assay on liver sections from SIRT^oe and NorUDCA/SIRT^oe mice after BDL confirmed attenuation of parenchymal injury in the latter. (G) CK19 IHC as well as (H) Sirius Red staining and aSMA IHC on liver sections, all followed by morphometric analyses, confirmed the beneficial impact of NorUDCA in BDL/SIRT^oe mice. All images at original magnification 10× or 20× (SIRT1). Values are mean ± SEM; n ≥ 5 animals/time point; *P < 0.05; **P < 0.01 (SIRT vs. NorUDCA/SIRT). Abbreviations: Ab, antibody; NorUDCA, nor‐ursodeoxycholic acid; NorUDCA/SIRT1^oe overexpressing mice that have been treated with NorUDCA.