MINIMAL EFFECT OF ACUTE EXPERIMENTAL HEPATITIS INDUCED BY LIPOPOLYSACCHARIDE D-GALACTOSAMINE ON BIOTRANSFORMATION IN RATS

When administered with D-galactosamine, lipopolysaccharide endotoxins produce a good experimental animal model of hepatitis. This galactosam ine plus endotoxin model has been used widely, but the acute effect of this fixed combination of two chemicals on hepatic and extrahepatic b iotransformation has not been determined. Therefore, either 2 or 4 hr after a single intraperitoneal dose of 300 mg/kg galactosamine plus 30 mu g/kg lipopolysaccharide was administered, serum, liver, kidney, in testine, and spleen were collected. Serum enzymes (alanine and asparta te aminotransferases, sorbitol dehydrogenase, and gamma-glutamyltransp eptidase) were elevated dramatically 2 and 4 hr after treatment. Cytoc hrome P450 monooxygenase activity toward benzo [a]pyrene was increased in kidney 4 hr after treatment, whereas dealkylation of 7-methoxycoum arin or 7-ethoxyresorufin was unchanged in any tissue at either time p oint. An increase in UDP-glucuranosyltransferase activity toward 4-met hylumbelliferone and 4-hydroxybiphenyl was noted in the intestine. Con jugation of 1-chloro-2,4-dinitrobenzene with glutathione was increased in intestine and spleen 2 hr after treatment. gamma-Glutamyltranspept idase activity was unaltered in all tissues studied. Reduced glutathio ne concentrations were increased significantly by different amounts de pending on which organs were studied 2 or 4 hr after treatment. These results indicate that galactosamine/lipopolysaccharide-induced liver i njury is not accompanied by major effects on the examined biotransform ation reactions. Copyright (C) 1996 Elsevier Science Inc.