title: Protective effects of luteolin against apoptotic liver damage induced by D-galactosamine/lipopolysaccharide in mice.
abstract: In this study, the protective effects of luteolin (1, a major component of Cirsium japonicum) were examined against d-galactosamine (GalN)/lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice received an intraperitoneal injection of 1 (25, 50, 100, and 200 mg·kg(-1)) 1 h before treatment with GalN (700 mg·kg(-1))/LPS (10 μg·kg(-1)). Treatment with GalN/LPS resulted in increased mortality and serum aminotransferase activity. These increases were attenuated by pretreatment with 1. Treatment with GalN/LPS induced an increase in the serum level of tumor necrosis factor-α (TNF-α) and protein expression of TNF-α receptor-associated death domain, and these increases were prevented by 1. In addition, 1 attenuated apoptosis induced by GalN/LPS treatment, which was analyzed using a caspase-3 and -8 activity assay, as well as by proapoptotic BH3-only protein and cytochrome c protein expression, and by a terminal deoxynuleotidyl transferase-mediated dUTP nick end-labeling method. After GalN/LPS injection, nuclear phosphorylated c-Jun levels showed a significant increase, which were attenuated by 1. The present findings suggest that luteolin ameliorates D-GalN/LPS-induced liver injury and that this protection is likely due to inhibition of the extrinsic and intrinsic apoptotic pathways.
authors: School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Korea.
authors: Woo-Cheol
authors: WC
authors: Lee
authors: Hyun Ah
authors: HA
authors: Jung
authors: Jae Sue
authors: JS
authors: Choi
authors: Yeong Shik
authors: YS
authors: Kim
authors: Sun-Mee
authors: SM
authors: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D031180:Cirsium / Q000737:chemistry*; D005688:Galactosamine / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy; D047311:Luteolin / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects; D000637:Transaminases / Q000032:analysis / Q000097:blood / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000097:blood
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D000637:Transaminases; D047311:Luteolin