Secoisolariciresinol and isotaxiresinol inhibit tumor necrosis factor-α-dependent hepatic apoptosis in mice

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DOIResolve DOI: http://doi.org/10.1016/j.lfs.2003.10.021
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TypeArticle
Journal titleLife Sciences
ISSN0024-3205
Volume74
Issue22
Pages27812792; # of pages: 12
SubjectSecoisolariciresinol; Isotaxiresinol; Apoptosis; Taxus yunnanensis; Hepatoprotective effect; TNF-α; D-Galactosamine; Lipopolysaccharide; Lignan
Abstracteffects of secoisolariciresinol (1) and isotaxiresinol (2), two major lignans isolated from the wood of Taxus yunnanensis, on tumor necrosis factor-α (TNF-α)-dependent hepatic apoptosis induced by D-galactosamine (d-GalN)/lipopolysaccharide (LPS) were investigated in mice. Co-administration of d-GalN (700 mg/kg) and LPS (10 μg/kg) resulted in a typical hepatic apoptosis characterized by DNA fragmentation and the formation of apoptotic bodies. Serum glutamic pyruvic transaminase (sGPT) and glutamic oxaloacetic transaminase (sGOT) levels were also raised at 8 h after d-GalN/LPS intoxication due to a severe necrosis of hepatocytes. Pre-administration of 1 or 2 (50, 10 mg/kg, i.p.) 12 and 1 h before d-GalN/LPS significantly reduced DNA fragmentation and prevented chromatin condensation, apoptotic body formation and hepatitis. Pro-inflammatory cytokines such as TNF-α and interferon-γ (IFN-γ) secreted from LPS-activated macrophages are important mediators of hepatocyte apoptosis in this model. Pre-treatment with 1 or 2 significantly inhibited the elevation of serum TNF-α and IFN-γ levels. In a separate experiment, both lignans had a significant dose-dependent protective effect on d-GalN/TNF-α-induced cell death in primary cultured mouse hepatocytes and TNF-α-mediated cell death in murine L929 fibrosarcoma cells. These results indicated that 1 and 2 prevent d-GalN/LPS-induced hepatic injury by inhibiting hepatocyte apoptosis through the blocking of TNF-α and IFN-γ production by activated macrophages and direct inhibition of the apoptosis induced by TNF-α.
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LanguageEnglish
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NPARC number21274279
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Record identifiercbdce5f1-6757-45f0-8885-e14d44d6e7df
Record created2015-03-09
Record modified2016-05-09
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