Abstract
The role of endotoxin in liver injury induced by D-Galactosamine (GalN) was investigated in rats in vivo, or by using isolated rat hepatocytes (in vitro). In colectomized rats, GalN produced little hepatotoxicity, while it induced severe liver damage by simultaneous administration of lipopolysaccharide (LPS). The liver injury induced by GalN was significantly inhibited by the treatment of nafamostadt mesilate, a complement inhibitor. Although GalN itself produced little hepatocytotoxicity on cultured hepatocytes in vitro, but severe hepatocyte necrosis was induced by GalN and endotoxemia (LPS-treated) rat serum obtained from rats 15 minutes after intravenous administration of LPS. However, LPS itself showed no hepatocytotoxicity in cultured hepatocytes. These results indicate that hepatocyte degeneration induced by GalN itself may be followed severe liver damage due to hepatocytotoxic factors like complement in endotoxemia rat serum.
