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Int Immunopharmacol. 2010 Mar;10(3):357-63. doi: 10.1016/j.intimp.2009.12.010. Epub 2009 Dec 28.

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

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  • 1Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, People's Republic of China.

Abstract

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 1h 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-kappaB activation, serum and hepatic tissues tumor necrosis factor-alpha (TNF-alpha) 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-kappaB activation to reduce TNF-alpha production.

Copyright 2009 Elsevier B.V. All rights reserved.

PMID:
20036342
[PubMed - indexed for MEDLINE]
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