Tetrandrine attenuates lipopolysaccharide-induced fulminant hepatic failure in d-galactosamine-sensitized mice

Fulminant hepatic failure (FHF) remains an extremely poor prognosis and high mortality; better treatments are urgently needed. Tetrandrine (TET), a traditional anti-inflammatory drug, has been reported to exhibit hepatoprotective activities in several liver injury models. We now investigated the effects and underlying mechanisms of TET on lipopolysaccharide (LPS) and d-galactosamine (d-GalN)-induced FHF in mice. TET (50, 100, and 200 mg/kg) was given intraperitoneally 1 h before LPS/d-GalN injection in mice. The mortality and liver injury was evaluated subsequently. The results showed that administering TET to mice reduced mortality and improved liver injury induced by LPS/d-GalN in a dose-dependent manner. In addition, TET dose-dependently inhibited LPS/d-GalN-induced NF-κB activation, serum and hepatic tissues tumor necrosis factor-α (TNF-α) production, caspase-3 activation and hepatocellular apoptosis, myeloperoxidase (MPO) activity, intercellular adhesion molecule-1 (ICAM-1) and endothelial cell adhesion molecule-1 (ECAM-1) expression. Our experimental data indicated that TET might alleviate the FHF induced by LPS/d-GalN through inhibiting NF-κB activation to reduce TNF-α production.