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)

While chickens infected with duck hepatitis virus showed no signs of clinical illness, their levels of hepatic cytochrome P-450 in response to phenobarbital induction and their microsomal aryl hydrocarbon hydroxylase activities in response to 3-methylcholanthrene induction were each found to correlate with the titer of virus recovered from the livers. These clear correlations indicate that avian hepatic drug metabolism is significantly modified during viral infection.
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PMID:Correlation of induced drug metabolism with titer of duck hepatitis virus in chickens. 19 18

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

1. Mitochondria and microsomal fractions have been isolated from liver biopsies from patients with alcoholic cirrhosis, cryptogenic cirrhosis or chronic aggressive hepatitis. 2. Cirrhotic livers yieled fewer mitochondria than normal liver. 3. The most significant change was a decrease in mitochondrial respiratory control. Cirrhotic microsomal fractions had a 50% diminution in cytochrome b5 and cytochrome P-450 content. 4. The two patients with chronic aggressive hepatitis showed similar mitochondrial and microsomal changes.
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PMID:Mitochondrial functions and content of microsomal and mitochondrial cytochromes in human cirrhosis. 88 31

Isaxonine phosphate or Nerfactor (2-isopropylaminopyrimidine) has been implicated in several cases of hepatitis which is reversible after withdrawal of the drug. In order to understand the cause of such hepatitis, the metabolic activation of isaxonine phosphate with different liver microsomes was investigated. The major metabolites were 5-hydroxyisopropylaminopyrimidine and 2-aminopyrimidine. Covalent binding to microsomal proteins was also detected. In vitro metabolic activation required intact microsomes, NADPH and O2 as cofactors and was cytochrome P-450 dependent. A sensitive fluorimetric assay of 5-hydroxyisaxonine was developed. The metabolism of isaxonine phosphate was compared in liver microsomes from rat, rabbit, dog, monkey and man and found to be qualitatively similar. Treatment of rats with phenobarbital increased the formation of 5-hydroxyisaxonine, while treatment with 3-methylcholanthrene increased the formation of 2-aminopyrimidine but decreased that of 5-hydroxyisaxonine. Inhibition and reconstitution experiments demonstrated that 5-hydroxylation of isaxonine was catalyzed by a cytochrome P-450. Metabolic oxidation of isaxonine phosphate using 5-[3H]isaxonine phosphate led to a total loss of tritium in 5-hydroxyisaxonine and partial loss of tritium in 2-aminopyrimidine and covalent binding to proteins.
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PMID:In vitro metabolism of isaxonine phosphate: formation of two metabolites, 5-hydroxyisaxonine and 2-aminopyrimidine, and covalent binding to microsomal proteins. 139 69

An autoantibody to liver cytosol was previously described in childhood autoimmune chronic active hepatitis type 2. The antigen, liver cytosol antigen type 1, was for the first time partially purified using gel filtration and ion exchange chromatography, and it was characterized using immunodiffusion, immunoblot and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the immunoprecipitate. Immunoblot detected a unique antigenic peptide at 62 kD from human cytosol and at 58 kD from rat cytosol. The same peptides were also detected when immunoprecipitates of liver cytosol antigen type 1 and autoantibodies to liver cytosol antigen were submitted to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A polymeric structure, probably a tetramer, is suggested for native liver cytosol antigen type 1 because in gel filtration chromatography liver cytosol antigen type 1 was eluted as a protein of a molecular weight between 240 and 290 kD when human liver cytosol was fractionated and between 220 and 270 kD from rat liver cytosol. Liver cytosol antigen type 1 is probably poor in carbohydrates because it was not stained by periodic acid-Schiff stain. The autoantibodies to liver cytosol were frequently found in association with antiliver kidney microsomal autoantibodies type 1, which are directed against the cytochrome P-450 of the IID6 subfamily. Antiliver kidney microsomal autoantibodies type 1 but not antiliver cytosol autoantibodies were found in association with antibodies to hepatitis C virus. Autoantibodies to liver cytosol antigen type 1 seem to be a more specific marker for autoimmune hepatitis type 2 than antiliver kidney microsomal antibodies type 1 autoantibodies.
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PMID:Characterization of the liver cytosol antigen type 1 reacting with autoantibodies in chronic active hepatitis. 139 95

Several hepatobiliary diseases appear to be mediated by the host immune response. They can be subdivided into those in which the immune reaction is against an infectious agent such as hepatitis viruses, those in which the immune reaction appears to be against an autoantigen expressed on hepatobiliary cells, and those due to alloimmunity. The existence of autoimmune liver diseases indicates a breakdown in the mechanisms responsible for self-tolerance. In HBV infection, the hepatocellular necrosis appears to be mediated by the host immune response against viral antigens expressed on the membranes of infected hepatocytes. Autoimmune chronic active hepatitis can be subdivided on the basis of differences in circulating autoantibodies. In classic type I autoimmune chronic hepatitis, autoantibodies are directed against non-organ- and non-species-specific antigens. Thus, they are unlikely to be involved in pathogenesis. In contrast, type II autoimmune chronic hepatitis is characterized by antibodies against specific cytochrome P-450 isoenzymes that appear to be expressed on the surface membrane of hepatocytes. Immunogenic cytochrome P-450 also can be induced by drug metabolism and haptenation. This indicates that environmental or medicinal xenobiotics may initiate autoimmune liver damage. Primary biliary cirrhosis is characterized by T-cell-mediated inflammation and destruction of interlobular and septal bile ducts and antibodies specific for epitopes of the 2-oxo-acid dehydrogenase multienzyme complex of mitochondria. The histopathologic lesion NSDC also is observed in alloimmune-mediated diseases such as CGVHD and rejection of liver allografts. PSC may be mediated by an immune response against endothelial cells of the peribiliary capillary plexus, with secondary reactions to bile duct epithelial cell antigens. The pathogenesis of alcoholic liver disease is multifactorial, but one component involves an immune response to acetaldehyde-protein adducts. Secondary sensitization of cell-mediated effector mechanisms, endothelial damage, and secretion of noxious cytokines appear to be involved in pathogenesis.
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PMID:Immune disorders of the liver and bile duct. 151 50

This study was carried out on 33 patients who were sero-positive for liver-kidney microsomal antibodies (LKM) in order to examine clinical features and the presence of underlying hepatitis C virus infection. Twenty-four sera were positive for antibodies against HCV (anti-HCV) as detected by enzyme immunoassay and confirmed by recombinant immunoblot assay. These patients had chronic liver disease and the majority of those treated with interferon responded favourably. Three of the nine anti-HCV-negative patients had idiopathic chronic hepatitis and two responded favourably to steroids. Two patients were diagnosed as having toxic hepatitis and the other four had various extrahepatic disorders without evidence of liver involvement. The immunoblotting analysis showed reactivity with a 50 kDa microsomal protein which presumably corresponded to cytochrome P-450 db1 both in anti-HCV-positive and -negative sera. In addition a few anti-HCV-positive sera also reacted with a 35 kDa microsomal antigen. Autoimmune markers different from LKM were absent in both groups. The high prevalence of antibodies to the hepatitis C virus among LKM-positive sera confirms that this infection plays a role in forms of chronic hepatitis that had previously been labelled autoimmune. In patients with LKM the presence of anti-HCV may help to forecast a therapeutic response to interferon, while its absence may forecast response to steroid therapy.
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PMID:Hepatitis C virus-related chronic liver disease with autoantibodies to liver-kidney microsomes (LKM). Clinical characterization from idiopathic LKM-positive disorders. 165 68

The 5-methylcytosine (5-mCyt) content in hepatic DNA of LEC rats was measured in order to know the mechanism by which changes in the cytochrome P-450 content and gamma-glutamyl transpeptidase activity occur. At the age of 10 or 16 weeks, there was no difference in the extent of DNA methylation as compared with that of control strain (LEA) rats. However, in the hepatoma tissues that developed later in LEC animals, the percentage of 5-mCyt in the liver of LEC rats was markedly reduced. A single i.p. dose of 5-azacytidine brought about a significant reduction of 5-mCyt content with a concomitant decrease of cytochrome P-450 and an increase in gamma-glutamyl transpeptidase activity in LEC rats, whereas no such changes occurred in the control LEA rats. These results suggest that LEC rats are highly sensitive to 5-azacytidine and that a reduction in hepatic DNA methylation may play some role in the predisposition of the rats to hepatitis or hepatoma.
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PMID:High sensitivity to 5-azacytidine in LEC rats, a strain with a metabolic predisposition to hepatitis and hepatoma: possible involvement of DNA methylation in the expression of cytochrome P-450 and gamma-glutamyl transpeptidase. 171 64

By the use of electron spin resonance (ESR) spectroscopy and of spin-trapping technique, the effects of ascorbic acid on the formation of the free radical intermediates due to isoniazid (INAH) and its metabolites were investigated with a microsomal system. When alpha-(4-pyridyl 1-oxide)-N-tert butylnitrone (4-POBN) was used as a spin trapping agent, the ESR signal due to hydrazine (Hy) was formed to be most intensive among others. Therefore, it was presumed that Hy is a potent intermediate to cause an INAH-induced hepatic injury. In the presence of ascorbic acid (AA), the free radical formation of Hy, INAH and acetyl hydrazine was significantly inhibited, suggesting that AA may affect the INAH-hepatitis. By the addition of inhibitors of cytochrome P-450 like metyrapone and CO, the generation of the radical from Hy decreased, confirming that the radical is formed by the cytochrome P-450 dependent microsome systems. The 4-POBN-trapped radical species generated from Hy was presumed to be the hydrazyl radical by the results of mass spectrometry.
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PMID:[Effects of ascorbic acid on the free radical formations of isoniazid and its metabolites]. 181 80

Marked alterations of hepatic drug-metabolizing enzymes were observed in hepatitis- and hepatoma-predisposed rats (LEC rats) fed a choline-deficient diet. The diet enhanced the development of hepatitis with severe jaundice. The levels of two major classes of cytochrome P-450, P-450PB and P-450MC, were markedly decreased. GST-Yp was dramatically increased, whereas GST-Ya, Yb1 and Yb2 were decreased. LEA rats (the control rats to LEC) fed a choline-deficient diet mimicked LEC rats fed a normal diet in terms of the above enzyme alterations, indicating that hypomethylation is involved in the pathogenesis of hepatitis and hepatoma in LEC rats. Such hypomethylation may initiate the hepatocytes that spontaneously develop hepatitis and hepatoma.
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PMID:Enhancing effect of a choline-deficient diet on alterations of hepatic drug-metabolizing enzymes in hepatitis- and hepatoma-predisposed rats (LEC rats). 190 19


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