Abstract
Treatment of experimental animals with D-galactosamine (GalN)/ lipopolysaccharide (LPS) causes lethal liver injury that is characterized by apoptosis of the hepatocyte. We analyzed the molecular mechanism of GalN/LPS-induced apoptosis of hepatocytes and examined the therapeutic effects of etoposide on GalN/ LPS-induced lethal liver injury. Serum tumor necrosis factor-α (TNF-α) levels were markedly increased in GalN/LPS-treated mice, and treatment with anti-TNF-α antibody of GalN/LPS-injected mice improved survival. The expression of tumor necrosis factor receptor-1 (TNFR1) mRNA, caspase 8 mRNA, and caspase 3 activity were enhanced in the liver of GalN/LPS-treated mice. Treatment of GalN/LPS-treated mice with etoposide markedly reduced lethality by preventing apoptosis of hepatocytes. The therapeutic effects of etoposide are thought to be caused by the enhancement of bcl-xL mRNA expression as etoposide did not alter serum TNF-α levels and TNFR1 mRNA expression. These findings suggest that antiapoptotic therapy is useful for the treatment of TNF-α-mediated liver diseases.
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© 2001 Springer Japan
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Hirono, S., Nakama, T., Tsubouchi, H. (2001). Molecular Mechanisms of D-Galactosamine/Lipopolysaccharide-Induced Fulminant Hepatic Failure in Mice and the Effects of Therapeutic Agents. In: Asakura, H., Aoyagi, Y., Nakazawa, S. (eds) Trends in Gastroenterology and Hepatology. Springer, Tokyo. https://doi.org/10.1007/978-4-431-67895-3_8
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DOI: https://doi.org/10.1007/978-4-431-67895-3_8
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-67993-6
Online ISBN: 978-4-431-67895-3
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