This study tested the hypothesis that high-cholesterol diet (HCD)-induced fatty liver disease could be ameliorated by rosuvastatin (Ros) and propylthiouracil (PTU) therapy. Thirty-two Zealand rabbits were equally divided into group 1 (sham-control), group 2 (HCD for 8 weeks), group 3 [HCD-Ros (20 mg/kg/day administration after 4-week HFD for 4 weeks)], group 4 [HCD-PTU (0.1% PTU in drinking water) with treatment course as group 3]. Liver weight, fibrosis, collagen deposition area, and serum levels of AST/ALT were highest in group 2, lowest in group 1, and significantly higher in group 4 than group 3 (all P<0.0001). The levels of inflammatory (TNF-α/NF-κB/IL-1ß/IL-6/MMP-9/VCAM-1/PAI-1/TLR-4, MyD88/IL-12/IFN-γ), oxidative stress (NOX-1/NOX-2/oxidized protein), apoptotic (Bax/cleaved-capase-3/PARP), fibrotic (Smad-3/TGF-ß), and mitochondria-damaged (cytosolic-cytochrome-C) proteins showed an identical pattern, whereas antiapoptotic (Bcl-2), mitochondrial-integrity (mitochondrial-cytochrome-C) and antioxidative (SIRT1/SIRT3) biomarkers exhibited an opposite pattern to fibrosis among the four groups (all P<0.0001). The cellular expressions of inflammatory (Kupffer/CD14/CD44), α-fetoprotein-positively stained biomarkers, apoptotic nuclei and fat cells displayed an identical pattern to fibrosis (all P<0.0001). In conclusion, Ros-PTU therapy attenuated liver fibrosis, inflammatory reaction and generation of oxidative stress and fatty liver after HCD challenge in rabbits.
Keywords: Oxidative stress; fatty liver; hypercholesterolemia; inflammation; liver fibrosis.