title: Sesamin ameliorates lipopolysaccharide/d-galactosamine-induced fulminant hepatic failure by suppression of Toll-like receptor 4 signaling in mice.
abstract: Sesamin has been described to exert anti-oxidant and anti-inflammatory properties. In present study, we investigated the potential effects and mechanisms of sesamin on lipopolysaccharide (LPS)-induced fulminant hepatic failure (FHF) in d-galactosamine (D-GalN)-sensitized mice. Our results showed that pretreatment with sesamin dose-dependently improved LPS/D-GalN-induced mortality and liver injury as indicated by reduced serum levels of aminotransferases and alleviated pathological damage as well as hepatocyte apoptosis in mice. Additionally, sesamin markedly attenuated LPS/D-GalN-induced adhesion molecules expression, and decreased neutrophils recruitment. Furthermore, sesamin inhibited LPS-induced tumor necrosis factor-alpha (TNF-α) production, p38 mitogen-activated protein kinases (MAPK) and NF-κB activation, and Toll like receptor (TLR) 4 expression in mice and in RAW264.7 macrophage cells. In summary, these results demonstrate that sesamin protects mice from LPS-induced FHF and the molecular mechanisms may down-regulate the expression of TLR4, block MAPK and NF-κB activation, decrease the production of TNF-α.
authors: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors: Li
authors: L
authors: Ma
authors: Department of Anatomy, Chongqing Medical University, Chongqing 400016, China.
authors: Xia
authors: X
authors: Gong
authors: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors: Ge
authors: G
authors: Kuang
authors: Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China.
authors: Rong
authors: R
authors: Jiang
authors: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors: Rongchun
authors: R
authors: Chen
authors: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China. Electronic address: jywan@cqmu.edu.cn.
authors: Jingyuan
authors: J
authors: Wan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D002460:Cell Line; D004149:Dioxoles / Q000627:therapeutic use*; D005688:Galactosamine; D017705:Lignans / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020011:Protective Agents / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000975:Antioxidants; D004149:Dioxoles; D017705:Lignans; D008070:Lipopolysaccharides; D020011:Protective Agents; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; C054125:sesamin
keywords: Fulminant hepatic failure; Lipopolysaccharide; Sesamin; TNF-α; Toll like receptor 4