PMID- 10421428 OWN - NLM STAT- MEDLINE DCOM- 19990805 LR - 20190701 IS - 0024-3205 (Print) IS - 0024-3205 (Linking) VI - 65 IP - 4 DP - 1999 TI - Acteoside inhibits apoptosis in D-galactosamine and lipopolysaccharide-induced liver injury. PG - 421-30 AB - 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. FAU - Xiong, Q AU - Xiong Q AD - Research Institute for Wakan-Yaku (Traditional Sino-Japanese Medicines), Toyama Medical & Pharmaceutical University, Japan. FAU - Hase, K AU - Hase K FAU - Tezuka, Y AU - Tezuka Y FAU - Namba, T AU - Namba T FAU - Kadota, S AU - Kadota S LA - eng PT - Journal Article PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Antioxidants) RN - 0 (Glucosides) RN - 0 (Lipopolysaccharides) RN - 0 (Phenols) RN - 0 (Plant Extracts) RN - 0 (Tumor Necrosis Factor-alpha) RN - 3TGX09BD5B (acteoside) RN - 7535-00-4 (Galactosamine) RN - 9007-49-2 (DNA) RN - EC 2.6.1.1 (Aspartate Aminotransferases) RN - EC 2.6.1.2 (Alanine Transaminase) SB - IM MH - Alanine Transaminase/blood MH - Animals MH - Antioxidants/*pharmacology MH - Apoptosis/*drug effects MH - Aspartate Aminotransferases/blood MH - Cell Survival MH - Chemical and Drug Induced Liver Injury/blood/pathology/*prevention & control MH - DNA/drug effects MH - Drug Synergism MH - Galactosamine/toxicity MH - Glucosides/*pharmacology MH - Lipopolysaccharides/toxicity MH - Liver/*drug effects/pathology MH - Liver Failure/blood/chemically induced/pathology/*prevention & control MH - Male MH - Mice MH - *Phenols MH - Plant Extracts/pharmacology MH - Tumor Necrosis Factor-alpha/metabolism/pharmacology EDAT- 1999/07/27 00:00 MHDA- 1999/07/27 00:01 CRDT- 1999/07/27 00:00 PHST- 1999/07/27 00:00 [pubmed] PHST- 1999/07/27 00:01 [medline] PHST- 1999/07/27 00:00 [entrez] AID - S0024320599002635 [pii] AID - 10.1016/s0024-3205(99)00263-5 [doi] PST - ppublish SO - Life Sci. 1999;65(4):421-30. doi: 10.1016/s0024-3205(99)00263-5.