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

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• 作者：Jung-Woo Kang^a ; Dong-Wook Kim^a ; Jae Sue Choi^b ; Yeong Shik Kim^c ; Sun-Mee Lee^a ; ^{sunmee@skku.edu}
• 关键词：d-Galactosamine/lipopolysaccharide ; Fulminant hepatic failure ; Inflammation ; Myeloid differentiation primary response gene 88 ; Toll-like receptor 4 ; Toll-receptor-associated activator of interferon
• 刊名：Food and Chemical Toxicology
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：57
• 期：Complete
• 页码：132-139
• 全文大小：1859 K

文摘

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 ¦Ìg/kg). Mice were treated intraperitoneally with scoparone 1 h 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 ¦ÊB and phosphorylated c-Jun, and levels of serum tumor necrosis factor-¦Á 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-¦Â 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.