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 galactosamine plus endotoxin model has been used widely, but the acute effect of this fixed combination of two chemicals on hepatic and extrahepatic biotransformation has not been determined. Therefore, either 2 or 4 hr after a single intraperitoneal dose of 300 mg/kg galactosamine plus 30 micrograms/kg lipopolysaccharide was administered, serum, liver, kidney, intestine, and spleen were collected. Serum enzymes (alanine and aspartate aminotransferases, sorbitol dehydrogenase, and gamma-glutamyltranspeptidase) were elevated dramatically 2 and 4 hr after treatment. Cytochrome P450 monooxygenase activity toward benzo-[a]pyrene was increased in kidney 4 hr after treatment, whereas dealkylation of 7-methoxycoumarin or 7-ethoxyresorufin was unchanged in any tissue at either time point. An increase in UDP-glucuronosyltransferase activity toward 4-methylumbelliferone and 4-hydroxybiphenyl was noted in the intestine. Conjugation of 1-chloro-2,4-dinitrobenzene with glutathione was increased in intestine and spleen 2 hr after treatment. gamma-Glutamyltranspeptidase activity was unaltered in all tissues studied. Reduced glutathione concentrations were increased significantly by different amounts depending on which organs were studied 2 or 4 hr after treatment. These results indicate that galactosamine/lipopolysaccharide-induced liver injury is not accompanied by major effects on the examined biotransformation reactions.
Omar H el-D
Indiana University School of Medicine, Medical Sciences Program, Bloomington 47405-4201, USA.
Sanders
R A
RA
Watkins
J B
JB
D000818:Animals; D001711:Biotransformation; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005688:Galactosamine; D014453:Glucuronosyltransferase / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D007422:Intestines / Q000201:enzymology; D007668:Kidney / Q000201:enzymology; D008070:Lipopolysaccharides; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000201:enzymology; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D008070:Lipopolysaccharides; D005688:Galactosamine; D003577:Cytochrome P-450 Enzyme System; D005723:gamma-Glutamyltransferase; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase