Scoparone attenuates D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure through inhibition of toll-like receptor 4 signaling in mice

Abstract

The purpose of this study was to investigate the protective effects and molecular mechanisms of scoparone on d-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced fulminant hepatic failure (FHF) in mice. FHF was induced in mice by intraperitoneal injection of D-GalN (800 mg/kg)/LPS (40 μg/kg). Mice were treated intraperitoneally with scoparone 1h before D-GalN/LPS treatment. Treatment with d-GalN/LPS markedly increased mortality, serum aminotransferase activity, and tolllike receptor 4 (TLR4) protein expression, and these increases were attenuated by scoparone. Treatment with d-GalN/LPS markedly increased myeloid differentiation primary response gene 88 protein expression, phosphorylation of p38, extracellular signal-regulated kinase and c-Jun N-terminal kinase, nuclear protein expression of nuclear factor κB and phosphorylated c-Jun, and levels of serum tumor necrosis factor-α and interleukin-6 and these increases were attenuated by scoparone. In addition, increased levels of toll-receptor-associated activator of interferon protein expression, phosphorylation of interferon (IFN) regulatory factor 3, and serum IFN-β level in D-GalN/LPS-treated mice were attenuated by scoparone. Our results suggest that scoparone attenuates d-GalN/LPSinduced liver damage by inhibition of the TLR-mediated inflammatory pathway.