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 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.
Gong
Xia
X
Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, People's Republic of China.
Luo
Fu-ling
FL
Zhang
Li
L
Li
Hong-zhong
HZ
Wu
Meng-jiao
MJ
Li
Xiao-hui
XH
Wang
Bin
B
Hu
Ning
N
Wang
Chang-dong
CD
Yang
Jun-qing
JQ
Wan
Jing-yuan
JY
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles; D044182:Benzylisoquinolines / Q000494:pharmacology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D005688:Galactosamine / Q000276:immunology*; D022781:Hepatocytes / Q000187:drug effects; D006967:Hypersensitivity / Q000473:pathology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008099:Liver / Q000201:enzymology / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D008111:Liver Function Tests; D051379:Mice; D008807:Mice, Inbred BALB C; D009195:Peroxidase / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013534:Survival; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001562:Benzimidazoles; D044182:Benzylisoquinolines; D008070:Lipopolysaccharides; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C009438:tetrandrine; D005688:Galactosamine; D009195:Peroxidase; D053148:Caspase 3; C017807:bisbenzimide ethoxide trihydrochloride