European journal of pharmacology, 2014-09, Vol.738, p.66-73
2014
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Protective effect of linarin against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure
- Ist Teil von
- European journal of pharmacology, 2014-09, Vol.738, p.66-73
- Ort / Verlag
- Netherlands
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Linarin was isolated from Chrysanthemum indicum L. Fulminant hepatic failure is a serious clinical syndrome that results in massive inflammation and hepatocyte death. Apoptosis is an important cellular pathological process in d-galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury, and regulation of liver apoptosis might be an effective therapeutic method for fulminant hepatic failure. This study examined the cytoprotective mechanisms of linarin against GalN/LPS-induced hepatic failure. Mice were given an oral administration of linarin (12.5, 25 and 50mg/kg) 1h before receiving GalN (800 mg/kg)/LPS (40 μg/kg). Linarin treatment reversed the lethality induced by GalN/LPS. After 6h of GalN/LPS injection, the serum levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor (TNF)-α, interleukin-6 and interferon-γ were significantly elevated. GalN/LPS increased toll-like receptor 4 and interleukin-1 receptor-associated kinase protein expression. These increases were attenuated by linarin. Linarin attenuated the increased expression of Fas-associated death domain and caspase-8 induced by GalN/LPS, reduced the cytosolic release of cytochrome c and caspase-3 cleavage induced by GalN/LPS, and reduced the pro-apoptotic Bim phosphorylation induced by GalN/LPS. However, linarin increased the level of anti-apoptotic Bcl-xL and phosphorylation of STAT3. Our results suggest that linarin alleviates GalN/LPS-induced liver injury by suppressing TNF-α-mediated apoptotic pathways.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0014-2999eISSN: 1879-0712DOI: 10.1016/j.ejphar.2014.05.024Titel-ID: cdi_proquest_miscellaneous_1837304054
- Format
- –
- Schlagworte
- Alanine Transaminase - metabolism, Animals, Apoptosis - drug effects, Apoptosis Regulatory Proteins - metabolism, Aspartate Aminotransferases - metabolism, Bcl-2-Like Protein 11, bcl-X Protein - metabolism, Caspase 3 - metabolism, Caspase 8 - metabolism, Chrysanthemum, Cytochromes c - secretion, Cytoprotection - drug effects, Cytosol - drug effects, Cytosol - secretion, Fas-Associated Death Domain Protein - metabolism, Galactosamine - pharmacology, Glycosides - pharmacology, Interferon-gamma - blood, Interferon-gamma - genetics, Interleukin-1 Receptor-Associated Kinases - metabolism, Interleukin-6 - blood, Interleukin-6 - genetics, Lipopolysaccharides - pharmacology, Liver - drug effects, Liver - pathology, Liver Failure, Acute - chemically induced, Liver Failure, Acute - metabolism, Liver Failure, Acute - pathology, Liver Failure, Acute - prevention & control, Male, Membrane Proteins - metabolism, Mice, Phosphorylation - drug effects, Proteolysis - drug effects, Proto-Oncogene Proteins - metabolism, RNA, Messenger - genetics, RNA, Messenger - metabolism, Signal Transduction - drug effects, STAT3 Transcription Factor - metabolism, Toll-Like Receptor 4 - metabolism, Tumor Necrosis Factor-alpha - blood, Tumor Necrosis Factor-alpha - genetics