Protective Effects of Luteolin against Apoptotic Liver Damage Induced by d-Galactosamine/Lipopolysaccharide in Mice
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文摘
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 mgkg鈥?) 1 h before treatment with GalN (700 mgkg鈥?)/LPS (10 渭gkg鈥?). 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-伪 (TNF-伪) and protein expression of TNF-伪 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.

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