Effect of anti-basic liver protein antibody-induced liver injury on hepatic drug-metabolizing enzymes in C57 BL/6J mice.
We attempted to produce a model mouse with a liver injury resulting from an immunological mechanism in C57BL/6J mice, and the effect of hepatitis on the hepatic microsomal mixed-function oxidase system was studied. An experimental immunological liver injury model was caused by the intravenous injection of an anti-basic liver protein (BLP) antibody in mice which had been previously immunized with normal rabbit IgG (RGG) and complete Freund's adjuvant. C57BL/6J strain mice showed the highest susceptibility to the immunological liver injury. Typical histopathological changes in the liver included submassive hepatocellular necrosis and infiltration of lymphocytes into the portal tract and sinusoid area in a necrotic lesion. The liver injury in this model was markedly inhibited by the administration of prednisolone (20 mg/kg, p.o.), cyclophosphamide (15 mg/kg, i.p.), levamisole (10 mg/kg, p.o.), glycyrrhizin (50 mg/kg, i.p.) and cepharanthine (10 mg/kg, i.p.), which act on the immune system. Twenty-four hours after the injection of anti-BLP antibody, the activities of aminopyrine N-demethylase, aniline hydroxylase and NADPH-cytochrome c reductase and the content of cytochrome P-450 were mostly reduced, whereas cytochrome b5 and NADH-ferricyanide reductase were not. These results suggest that the experimental liver injury model in C57BL/6J mice is useful as a model of liver injury model, and its hepatitis was shown to inhibit the cytochrome P-450-dependent biotransformation of drugs in the mouse.
Ishikawa
M
M
Department of Pharmacology and Toxicology, Tohoku College of Pharmacy, Sendai, Japan.
Takayanagi
Y
Y
Sasaki
K
K
D000818:Animals; D000906:Antibodies / Q000276:immunology; D006505:Hepatitis / Q000201:enzymology* / Q000473:pathology; D008099:Liver / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D011817:Rabbits; D013045:Species Specificity
D000906:Antibodies; D008565:Membrane Proteins; D006899:Mixed Function Oxygenases