Acteoside inhibits apoptosis in D-Galactosamine and lipopolysaccharide-induced liver injury

• Published in: Life sciences (1973) Vol. 65; no. 4; pp. 421 - 430
• Main Authors: Xiong, Quanbo, Hase, Koji, Tezuka, Yasuhiro, Namba, Tsuneo, Kadota, Shigetoshi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 1999
• Subjects: acteoside; Alanine Transaminase - blood; Animals; Antioxidants - pharmacology; apoptosis; Apoptosis - drug effects; Aspartate Aminotransferases - blood; Cell Survival; Chemical and Drug Induced Liver Injury - blood; Chemical and Drug Induced Liver Injury - pathology; Chemical and Drug Induced Liver Injury - prevention & control; D-galactosamine; DNA - drug effects; Drug Synergism; Galactosamine - toxicity; Glucosides - pharmacology; lipopolysaccharide; Lipopolysaccharides - toxicity; Liver - drug effects; Liver - pathology; Liver Failure - blood; Liver Failure - chemically induced; Liver Failure - pathology; Liver Failure - prevention & control; Male; Mice; necrosis; Phenols; Plant Extracts - pharmacology; reactive oxygen intermediates; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - pharmacology; tumor necrosis factor-α; D-galactosamine; acteoside; necrosis; tumor necrosis factor-α; apoptosis; lipopolysaccharide; reactive oxygen intermediates
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(99)00263-5

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
μg
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 l h prior to
d-GalN/LPS intoxication significantly inhibited hepatic apoptosis, hepatitis and lethality. Tumor necrosis factor-α (TNF-α) 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-α, but it partially prevented
in vitro TNF-a (100
ng
ml
)-induced cell death in
d-GalN (0.5 mM)-sensitized hepatocytes at the concentrations of 50, 100 and 200 μM. 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-α-dependent hepatic apoptosis.