Modification of Pathologic Changes in Toxicological Studies due to Endotoxin Derived from Intestinal Flora II. Effects on Galactosamine-induced Liver Injury with Lactulose, Cyclophosphamide, or Ricinoleic Acid in Rats

抄録

In order to examine the variation of pathologic modifications with endogenous endotoxin, galactosamine (GalN) 400 mg/kg was administered intraperitoneally to male rats combined with lactulose (LTS) 6,000 mg/kg/day × 7 days, po, cyclophosphamide (CPM) 100 mg/kg, ip, or ricinoleic acid (RA) 2,000 mg/body, po. LTS was used for alteration of intestinal flora, CPM for depression of local intestinal immune system, and RA for disruption of intestinal epithelial barrier. In the GalN alone group, hepatic changes such as morphologic activation of Kupffer cells, and degeneration and necrosis of hepatocytes in the liver were observed microscopically. However, there were no remarkable changes in the liver in the GalN/LTS group. In the GalN/CPM and GalN/RA groups, although damage of the liver parenchymal cells was milder than those of the GalN alone group, activation of Kupffer cells and mononuclear cell aggregation in the GalN/RA group were more prominent than the GalN alone group. From the results, as to occurrence of pathologic changes due to endogenous endotoxin, we suggest that the situation of the intestinal flora and the intestinal epithelial barrier, and the balance between quantity of endotoxin and the RES function are important. We concluded that, according to toxicity of a test compound, it is necessary to consider the influence of endogenous endotoxin for assessment and judgement of the toxicity study's results.