title: 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.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Jung-Woo
authors.initials: JW
authors.lastname: Kang
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
authors.forename: Sun-Mee
authors.initials: SM
authors.lastname: Lee
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D019306:Artemisia / Q000737:chemistry; D003374:Coumarins / Q000494:pharmacology*; D005688:Galactosamine / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016899:Interferon-beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000410:Alanine Transaminase; D003374:Coumarins; D005688:Galactosamine; D016899:Interferon-beta; D015850:Interleukin-6; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse; C493487:Tlr4 protein, mouse; C018145:scoparone