The fate of intravenously injected endotoxin in normal rats and in rats with liver failure

The elimination of endotoxin from the blood was studied in rats with D-galactosamine–induced liver failure and in normal controls after intravenous injection of various doses of endotoxin. Endotoxin was found to localize in liver tissue by immunohistochemical staining with factor C, which is derived from amebocyte lysate of the horseshoe crab and which reacts specifically with endotoxin. Before injection, the blood endotoxin concentrations were normal both in control rats and in rats with liver failure. The blood concentrations of endotoxin were significantly higher after intravenous injection of endotoxin in the D-galactosamine–induced liver failure group (p<0.05) and decreased much more slowly (p<0.05). Endotoxin concentrations were also significantly higher after in vitro incubation with plasma from rats with liver failure (p<0.05). After intravenous injection of endotoxin (1 mg/kg), endothelial and Kupffer cells in the liver sinusoids were positively stained for endotoxin in the control group, but not stained or faintly stained in the liver failure group. Endotoxemia in liver failure thus results from reduced inactivation of endotoxin in plasma and from impaired hepatic clearance. (HEPATOLOGY 1994;19:1251–1256.)