title: Polydatin protects against lipopolysaccharide-induced fulminant hepatic failure in D-galactosamine-sensitized mice.
abstract: Fulminant hepatic failure (FHF) is a devastating clinical syndrome with extremely poor prognosis and high mortality. Therefore, better treatment is urgently needed. Polydatin (PD), a traditional anti-inflammatory drug, has been described to protect against liver injury induced by certain hepatotoxins. The present study investigated the protective effect of PD against lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced FHF in mice and the underlying mechanism. Mice were pretreated with an increasing dose of PD (10, 30, and 100 mg/kg), following LPS/D-GalN challenge. The liver injury was assessed biochemically and histologically. We found that PD exerted a protective effect on LPS/D-GalN-induced FHF as evidenced by reducing sera alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, diminishing liver histopathological injury, and lowering mortality in a dose-dependent manner. In addition, pretreatment mice with PD dose-dependently suppressed tumor necrosis factor-alpha (TNF-alpha) production, myeloperoxidase (MPO) activity, intercellular adhesion molecule-1 (ICAM-1) and endothelial cell adhesion molecule-1 (ECAM-1) expression, caspase-3 activation, and transcription factor nuclear factor-kappa B(NF-kB) activity induced by LPS. These results suggested that PD could effectively protect from LPS/D-GalN-induced FHF and the protective effect afforded by PD probably contributed to reduce TNF-alpha production via inhibiting NF-kB activation.
authors.affiliation: Chongqing Medical University, Chongqing, China.
authors.forename: M J
authors.initials: MJ
authors.lastname: Wu
authors.forename: X
authors.initials: X
authors.lastname: Gong
authors.forename: R
authors.initials: R
authors.lastname: Jiang
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: X H
authors.initials: XH
authors.lastname: Li
authors.forename: J Y
authors.initials: JY
authors.lastname: Wan
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000032:analysis; D005688:Galactosamine / Q000633:toxicity*; D005960:Glucosides / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008070:Lipopolysaccharides / Q000633:toxicity*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D015815:Cell Adhesion Molecules; C568779:ESAM protein, human; D005960:Glucosides; D008070:Lipopolysaccharides; D016328:NF-kappa B; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D005688:Galactosamine; D053148:Caspase 3; C058229:polydatin