Acteoside inhibits apoptosis in D-galactosamine and lipopolysaccharide-induced liver injury.
We assessed the effect of acteoside, a naturally occurring antioxidative phenylethanoid, on hepatic apoptosis and the subsequent liver failure induced by D-Galactosamine (D-GalN) and lipopolysaccharide (LPS). A co-administration of D-GalN (700 mg/kg) and LPS (35 microg/kg) to mice evoked typical hepatic apoptosis characterized by DNA fragmentation and apoptotic body formation, resulting in fulminant hepatitis and lethality of mice. Pre-administration of acteoside at 10 or 50 mg/kg subcutaneously at 12 and 1 h prior to D-GalN/LPS intoxication significantly inhibited hepatic apoptosis, hepatitis and lethality. Tumor necrosis factor-alpha (TNF-alpha) secreted from LPS-stimulated macrophages is an important mediator of apoptosis in this model. Acteoside showed no apparent effect on the marked elevation of serum TNF-alpha, but it partially prevented in vitro TNF-alpha (100 ng/ml)-induced cell death in D-GalN (0.5 mM)-sensitized hepatocytes at the concentrations of 50, 100 and 200 microM. These results indicated that D-GalN/LPS-induced hepatic apoptosis can be blocked by an exogenous antioxidant, suggesting the involvement of reactive oxygen intermediates (ROIs) in TNF-alpha-dependent hepatic apoptosis.
Xiong
Q
Q
Research Institute for Wakan-Yaku (Traditional Sino-Japanese Medicines), Toyama Medical & Pharmaceutical University, Japan.
Hase
K
K
Tezuka
Y
Y
Namba
T
T
Kadota
S
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D002470:Cell Survival; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D004247:DNA / Q000187:drug effects; D004357:Drug Synergism; D005688:Galactosamine / Q000633:toxicity; D005960:Glucosides / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D017093:Liver Failure / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D010636:Phenols; D010936:Plant Extracts / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D059808:Polyphenols
D000410:Alanine Transaminase; D000975:Antioxidants; D001219:Aspartate Aminotransferases; D004247:DNA; D005688:Galactosamine; D005960:Glucosides; D008070:Lipopolysaccharides; D010636:Phenols; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C058956:acteoside; D059808:Polyphenols