The enhancement of liver injury by lipopolysaccharide in an experimental drug-induced allergic hepatitis model.
When guinea pigs sensitized with trinitrophenylated (TNPed) liver protein 1 (LP1) were intravenously injected with TNPed isolated hepatocytes, remarkable hepatic cell injury was induced 24 hours later. In this experimental model, drug-induced allergic liver injury was induced by using trinitrobenzen sulfonic acid (TNBS) as the hapten and LP1 as the carrier. When these sensitized guinea pigs were intravenously injected with 10 micrograms of lipopolysaccharide (LPS) along with TNPed isolated hepatocytes, serum AST and ALT levels were remarkably higher than those of the guinea pigs not injected with LPS. Hepatic cell necrosis was also more extensive, and some bleeding was observed. Although none of the guinea pigs died even after 24 hours, when 50 micrograms of LPS was injected, many of the guinea pigs started to die and the survival rate was 5% at 24 hours. These results suggested that LPS enhanced liver injury in this experimental drug-induced allergic liver injury model.
Third Department of Internal Medicine, Osaka City University Medical School, Japan.
Y
Y
Mizoguchi
T
T
Shin
M
M
Mizuno
S
S
Seki
K
K
Kobayashi
S
S
Morisawa
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D004337:Drug Carriers; D006168:Guinea Pigs; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000276:immunology; D008297:Male; D008565:Membrane Proteins; D011506:Proteins; D014302:Trinitrobenzenesulfonic Acid
D004337:Drug Carriers; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011506:Proteins; D014302:Trinitrobenzenesulfonic Acid