Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concentration of cytochrome P-450 and activities of the microsomal enzymes aryl hydrocarbon hydroxylase and ethylmorphine demethylase were measured in hepatic tissue obtained at biopsy from 69 patients. Antipyrine half-life (AP t1/2) was measured simultaneously as an in vivo marker of drug metabolism. Values for each index of the drug-metabolizing system varied greatly, but the mean values in groups of patients with mild hepatitis or inactive cirrhosis did not differ significantly from those of controls. Hepatic cytochrome P-450 content and aryl hydrocarbon hydroxylase activity were lower in patients with severe hepatitis or active cirrhosis than in controls, but ethylmorphine demethylase activity was unchanged in the patients. Drug ingestion was associated with enhancement of drug-metabolizing enzymes in all patients but those with severe liver disease; ethylmorphine demethylase activity was enhanced proportionately more than aryl hydrocarbon hydroxylase activity or cytochrome P-450 concentration. The observation that aryl hydrocarbon hydroxylase and ethylmorphine demethylase activities are influenced to a different extent by liver disease and also by drug ingestion indicates functional heterogeneity of the hepatic microsomal drug-metabolizing system in man. Correlations between t1/2 and hepatic drug oxidases were weak, even when allowance was made for variation in liver size. Thus, the rate of drug metabolism in vivo assessed by measuring AP t1/2 does not appear to be closely related to the activity of some hepatic drug-metabolizing enzymes.
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PMID:Drug metabolism in liver disease: activity of hepatic microsomal metabolizing enzymes. 48 96

Anti-liver microsomes (anti-LM) autoantibodies in patients with dihydralazine-induced hepatitis were found to react specifically with cytochrome P4501A2 (P4501A2) but not with P4501A1 expressed in yeast and bacteria. These results were confirmed by immunoinhibition of methoxyresorufin-O-demethylase activity (supported by the P4501A subfamily); anti-LM antibodies more strongly inhibited this activity in yeast expressing P4501A2 than in yeast expressing P4501A1. Anti-LM were shown to be specific to the disease; in three cases, these autoantibodies were present at high titers during disease, whereas the titers decreased upon recovery and became undetectable a few months after recovery. Thus, there exists a time-dependent relationship between the disease and the autoantibodies, which does not prove that the autoantibodies are causative of the hepatitis; they might only be a marker. The inductive capacity of dihydralazine toward P450 was also studied. In rats treated in vivo and in human hepatocytes treated in vitro with dihydralazine, a 2-fold increase in P4501A2- and P4501A-supported monooxygenase activities was found. The levels of the other P450 isoforms tested were unchanged during treatment, both in vivo in rats and in vitro in cultures of human hepatocytes. In human hepatocytes, dihydralazine produced a dose-dependent increase in the level of P4501A up to 0.1 mM; induction of P4501A was less strong at 0.2 mM and disappeared at 0.5 mM. The same treatment did not change the level of P4503A4, taken as control. The strong heterogeneity in the expression of P4501A enzymes in human liver and the capacity of these enzymes for induction by dihydralazine and by other compounds might be predisposing factors in this autoimmune disease.
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PMID:Anti-liver microsomes autoantibodies and dihydralazine-induced hepatitis: specificity of autoantibodies and inductive capacity of the drug. 151 26

The hepatoprotective agents silybinin, essentiale and eplir (the complex of phospholipids and caratinoids from the mud) prevent in D-galactosamine-induced intoxication of rats the development of hepatitis, hepatocyte necrosis, a decrease in hepatocytes of the activity of the enzymes of mitochondria and endoplasmic reticulum, labilization of lysosomes. These drugs stimulate D-galactosamine-suppressed antitoxic function of the liver: they increase the contents of RNA, cytochromes P-450, b5, the activity of amidopyrine-D-demethylase, hydroxylases of hexobarbital and aniline, improve the activity of the respiratory chain of microsomes, counteract inactivation of cytochrome P-450 into cytochrome P-420. Essentiale and eplir activate conjugation of xenobiotics with reduced glutathione.
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PMID:[The correction with hepatic protectors of structural metabolic disorders in the liver in D-galactosamine poisoning]. 236 52

Adult female B6C3F1 mice were gavaged with 4,4'-thiobis-(6-t-butyl-m-cresol) (TBBC) in corn oil at doses of 10, 100, or 200 mg/kg daily for 14 consecutive days. There was no overt toxicity, as manifested by grossly observable behavioral changes, decreased growth rate over the exposure period, or mortality. There were also no marked effects on serum chemistries or hematology, with the exception of a significant increase (41%) in the number of leukocytes at the highest dose. Absolute differential counts indicated that significant increases occurred in the number of lymphocytes (31%) and neutrophils (177%). Studies with bone marrow indicated a significant 30% increase in the number of cells/femur from animals treated with the highest dose of TBBC. The number of macrophage progenitors (CFU-M)/femur was significantly increased by 28%, while the number of granulocyte-monocyte progenitors (CFU-GM)/femur was nonsignificantly increased by 20% in the high dose animals. The weight of both the spleen and liver was increased in a dose-related fashion, although the histopathology of the spleen of TBBC-treated mice was not different from control. The livers of mice receiving the high dose showed mild focal hydropic degeneration, mild hepatitis, and a slight increase in the number of Kupffer cells. No other organs were affected. Liver microsomal protein and cytochrome P-450 levels were increased in a dose-related fashion. Enzyme activities of aminopyrine demethylase and aniline hydroxylase, but not arylhydrocarbon hydroxylase, were also increased in a dose-related fashion.
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PMID:An immunotoxicological evaluation of 4,4'-thiobis-(6-t-butyl-m-cresol) in female B6C3F1 mice. 1. Body and organ weights, hematology, serum chemistries, bone marrow cellularity, and hepatic microsomal parameters. 339 95

The authors have studied the action of fluorine, administered by inhalation, on the liver metabolism of a chemical carcinogen: dimethylnitrosamine (DMN). The results demonstrate a decrease in the level of cytochrome P450 and in the activity of benzo(a)pyrene hydroxylase in animals treated with DMN or DMN + HF. The greater inhibition in the presence of HF is paralleled by a decrease in the weight of the liver and in the synthesis of liver microsomal proteins. This reduction of activity (with the exception of dimethylnitrosamine demethylase which is unaffected) is supported by the result of the histological examinations showing two different types of lesion-necrotic toxic hepatitis and post-hepatitic cirrhosis - the frequency of which is much higher in the presence of fluorine.
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PMID:[Effect of HF on the hepatic metabolism of dimethylnitrosamine in the rat]. 667 13

Chenophalk (chenodeoxycholeic acid) was given to Wistar rats, including intact animals and those with chronic toxic hepatitis, in daily oral dose of 15 mg/kg body weight during 11 days. Chronic toxic hepatitis was induced by 7 subcutaneous injections of carbon tetrachloride (0.3 ml of 50% oil solution per kg body weight) each three days. Chenophalk was shown to impair bile crystallization. It enhanced demethylase activity, elevated the levels of cytochromes P-450 and b5 in the liver microsomal fraction, and decreased lipid peroxidation just after injection. The agent normalized oxygen tension in the liver tissue, which had been reduced by carbon tetrachloride. Chenophalk caused disturbances in the structure of the liver and in microcirculation early after injection, showing a tendency to normalize the histostructure of the liver.
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PMID:[The effect of chenophalk on the liver function of intact animals and in experimental hepatitis]. 814 61

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.
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PMID:Effect of anti-basic liver protein antibody-induced liver injury on hepatic drug-metabolizing enzymes in C57 BL/6J mice. 828 50

The aim of this study was to investigate prophylactic and curative effect of polyphenolic extract of Ichnocarpus frutescense against carbon tetrachloride and tamoxifen induced hepatotoxicity in rats. Carbon tetrachloride and tamoxifen caused liver damage in rats manifested by significant rise in serum enzymes levels. Models of carbon tetrachloride and tamoxifen intoxication elicited significant declines in the reduced glutathione concomitant with significant elevations in malondialdehyde levels. The oral administration of polyphenolic extract to carbon tetrachloride and tamoxifen intoxicated ats, produced significant increments in the reduced glutathione concomitant with significant decrements in malondialdehyde and liver transaminases levels. Prophylactic and curative treatments with the polyphenolic extract generally resulted in a relatively good protection against both carbon tetrachloride and tamoxifen intoxicated rats. The histopathological changes of liver sections showed an improved histological appearance. The extract inhibits CYP monoxygenases aminopyrine-N-demethylase and aniline hydroxylase, suggesting a plausible hepatoprotective mechanism. However prophylactic treatment with the polyphenolic extract exhibited a higher activity compared to curative treatment. The normalization of phenobarbitone induced sleeping time suggests the restoration of liver CYP enzymes. The study shows that hepatoprotective activity of polyphenol extract is by regulating the levels of hepatic microsomal drug metabolising enzymes. These results supported the use of this plant for the treatment of hepatitis in oriental traditional medicine.
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PMID:Protective and curative effects of polyphenolic extracts from Ichnocarpus frutescense leaves on experimental hepatotoxicity by carbon tretrachloride and tamoxifen. 2130 Oct 12