title: Mechanism investigation of dioscin against CCl4-induced acute liver damage in mice.
abstract: The mechanisms of the ameliorating effects of dioscin against CCl(4) induced acute liver damage are investigated in this study. Dioscin significantly inhibited (p<0.01) the increases of serum ALT and AST activities compared with the CCl(4)-treated animals. The hepatic lipid peroxidation formation and, concentrations of TNF-α and IL-6 were also decreased. Liver histopathologic studies and a DNA laddering assay indicated that dioscin protected hepatocytes against CCl(4)-induced apoptosis and necrosis. Furthermore, dioscin decreased the protein expressions of Fas/FasL, increased Bcl-2/Bax ratio, inhibited the release of cytochrome c from mitochondrion to cytosol and attenuated CCl(4)-induced caspase-3 and -8 activities. The expressions of ICAM-1, vimentin, prohibitin, HGF, c-MET and GSTA1 were also regulated by dioscin and iNOS was also involved in the effects of this agent. These protective effects against CCl(4) induced acute liver damage might be through inhibiting lipid peroxidation, inflammatory cytokines, necrosis and apoptosis, and dioscin shows promise for development toward the treatment of acute chemically mediated liver injury.
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors.forename: Binan
authors.initials: B
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
authors.forename: Yousong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Cong
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors.forename: Lianhong
authors.initials: L
authors.lastname: Yin
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, 116044, China. Electronic address: jinyongpeng2008@126.com.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D020011:Protective Agents; D009569:Nitric Oxide; C019357:dioscin; D008315:Malondialdehyde; D002251:Carbon Tetrachloride; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D013482:Superoxide Dismutase; D053148:Caspase 3; D053181:Caspase 8; D005978:Glutathione; D004144:Diosgenin