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 development of hepatitis, induced in 48 rats by the administration of galactosamine (GalN) in varying doses, was studied with the use of substrate and enzyme histochemical techniques. The so-called atypical glycogen, which is at first highly resistant to diastase, was shown to be digestible after deamination. The increasing accumulation of atypical glycogen during the course of GalN-hepatitis conceals the loss of normal glycogen when the PAS-reaction is used. Nevertheless glycogenolysis could also be demonstrated by the increasing activity of phosphorylase. The acid phosphatase activity was progressively diminished, which was interpreted as signifying early lysosomal damage. G6Pase activity remained nearly constant but SDH showed a decrease in activity after 12 h. These histochemical results are considered to provide deeper insight into the pathological mechanism of GalN-hepatitis.
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PMID:Histochemical studies on carbohydrate metabolism in rat liver after galactosamine administration. 3 60

We have induced acute hepatitis in rats with the amino sugar Galactosamine by i.p. injection. The development of the disease was controlled by measurements of several metabolites and enzymes in serum, and light and electronic microscopy. Tyrosine transaminase was induced by i.p. injection of Cortisol, that increases ten times enzyme activity in liver parenchyma of normal rats. This inductive phenomenon cannot be observed in animals with galactosamine hepatitis. We discuss the probable mechanism and their relationship with some forms of viral hepatitis in human beings.
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PMID:Induction of tyrosine aminotransferase in galactosamine hepatitis. 4 46

D-Galactosamine hepatitis cannot be induced in rapidly replicating liver tissue at various times after induction of proliferation. Proliferation was induced by administration of alpha-hexachlorocyclohexane. The morphological features of galactosamine hepatitis do not appear or are very mild. The onset of DNA synthesis is delayed to about 12 hrs as also shown in partially hepatectomized rats.
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PMID:Investigations on d-galactosamine hepatitis after pretreatment with alpha-hexachlorocyclohexane. 5 71

The serum concentrations of alpha-fetoprotein of rats following experimental galactosamine-induced liver-cell necrosis accurately reflect the severity of preceding liver-cell damage as determined by elevation of serum transaminases. There is a very close correlation between the highest SGOT or SGPT serum activity found 1-2 days after induction of necrosis and the subsequent elevation of alpha-fetoprotein at 2-6 days. Elevations of alpha-fetoprotein are associated in time with restitutive proliferation of the damaged liver. These experimental results clarify the temporal relationship between alpha-fetoprotein and repair of liver-cell damage, which has been suggested by similar observations in cases of patients who have acute or sub-acute viral hepatitis. The correlations support the concept that serum alpha-fetoprotein concentrations may be used as a prognostic indicator of the extent and course of fulminatn or subacute hepatitis.
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PMID:Serum alpha-fetoprotein. A prognostic indicator of liver-cell necrosis and regeneration following experimental injury by galactosamine in rats. 6 10

Enzyme deviations in injured livers were studied by analyzing isozyme patterns of phosphorylase using a newly developed electrophoretic method, which separates six molecular species of this enzyme, i.e. M,FM,F,L,L', and FL'. In hepatic injuries caused by CCl4 and galactosamine intoxications of rats, F appeared in early stages and L' (and FL') in later stages of the injuries with a concurrent decrease or loss of L, which is a sole isozyme component of adult liver. In injured livers of patients with hepatitis and cirrhosis of the liver, increases in FL' activity were also found. Appearance of F was found only in hepatocellular carcinoma. The results obtained with phosphorylase isozyme analysis support the idea that an undifferentiated gene expression takes place in the injured livers of non-malignant hepatic disorders.
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PMID:Studies of liver phosphorylase in hepatic injuries II. Alteration in isozyme pattern. 15 93

One of the most sensitive and specific signs of the galactosamine effect upon the rat liver cell is the appearance of PAS-positive and diastase-resistant granules within the cytoplasm of hepatocytes. Light-microscopic, histochemical, biochemical, and electron-microscopic findings reveal that the appearance of these ADB (= atypical dense bodies) depends upon a working glycogen metabolism at the time of GalN treatment. The ADB are composed of particles resembling, due to shape and size, ribosomes and beta particles of glycogen. Most of them are surrounded by the rER, but they are never enclosed by a limiting membrane. Due to sequential changes they can be generally classified into three types; the early, the intermediate, and the late type. In seven experiments it can be shown, that the appearance of the ADB depends upon the time and dosage after GalN treatment. They occur even if an additional treatment with galactose or uridine prevents the liver from the features of a hepatitis, as also shown in the livers of newborn animals up to 3 weeks of age. The histochemical response against various glucosidases, hexosaminidases, pronase, and RNAse as well as against various fixatives indicates that ADB are composed of, at least, two different constituents, the former RNAse-sensitive and visible with routine light-microscopic staining procedures, the latter RNA-resistant, PAS-positive, and invisible after staining with H & E or toluidine blue. The latter is diastase-resistant, suggesting that this portion of ADB does not represent the usual glycoproteins but some abnormal metabolite of glycogen. The ADB can be detected with maximal accumulation in the cytoplasm of hepatocytes at that time when the glycogen content determined in the liver homogenate by biochemical methods is greatly reduced.
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PMID:The appearance and degradation of specific hepatocellular cytoplasmic inclusion bodies in rat liver due to D-galactosamine. I. The relation between the amount of liver glycogen and the appearance of the atypical dense bodies in the liver cell. 18 85

In order to evaluate the pathogenesis of galactosamine hepatitis, the action of galactosamine on mast cells, and alteration in the complement system suring the course of this experimental injury were studied. It has been previously demonstrated that rat livers after colectomy are refractory to galactosamine-induced liver cell necrosis and inflammation. For this reason colectomized animals were used to see whether the biochemical alterations produced by this aminosugar and thought to be responsible for cell death developed. Results showed: 1. galactosamine potently degranulates mast cells in vivo and in vitro, 2. the complement system is a) activated during the course of galactosamine hepatitis, probably by circulating endotoxins, and b) is essential for liver cell death in galactosamine hepatitis, and 3. colectomy does not prevent biochemical changes known to occur during galactosamine metabolism. It is concluded that death of galactosamine-injured liver cells is triggered by extrahepatocellular mechanisms, which lead ultimately to an activated complement system by endotoxins. It is postulated that related mechanism may also occur in viral hepatitis and in fulminant hepatic failure in man.
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PMID:On the pathogenesis of galactosamine hepatitis. Indications of extrahepatocellular mechanisms responsible for liver cell death. 41 92

Role of lipid peroxidation on lysosomal instability in liver tissue was investiaged in an experimental model of D-galactosamine hepatitis in rats fed on vitamin E (V.E) deficient diet. Administration of D-galactisamine to V.E deficient rats resulted in a sudden increase of serum glutamic oxaloacetic transaminase (sGOT), glutamic pyruvic transaminase (sGPT), lipid peroxide value, as well as beta-glucuronidase and acid phosphatase activity examined as markers of lysosomal enzymes, when compared with control rats fed on V.E supplemented diet. Lipid peroxide in the liver tissue also showed significant increase in V.E deficient rats. In contrast, beta-glucuronidase and acid phosphatase in the liver tissue were found to decrease in V.E deficient rats by the administration of D-galactosamine, indicating that the enzymes in the lysosome were entirely released outside the liver cells as a result of cell destruction. It is concluded that the increase of lipid peroxide causes the instability of lysosomal membranes and releases various kinds of hydrolytic enzymes to lead further to cell damage. V.E might act on inhibiting lipid peroxidation to stabilize lysosomal membranes.
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PMID:Lipid peroxidation and lysosomal enzymes in D-galactosamine hepatitis and its protection by vitamin E. 44 84

There are many reports showing a close relation between polyamine metabolism and tissue growth or recovery of damaged tissues, such as regenerating liver. Thus, changes in polyamine metabolism in the livers from rats treated with D-galactosamine, an inducer of experimental hepatitis, were studied. The activity of ornithine decarboxylase started to increase 14 hr after administration of galactosamine and reached 30 times the normal activity at about 25 hr, the time of maximum severity of hepatitis. The content of putrescine increased to about 10 times the control value. After increases in the putrescine content and ornithine decarboxylase activity, the hepatitis started to diminish. Increases in the activity of S-adenosylmethionine decarboxylase and the content of spermidine were observed 33-37 hr after administration of galactosamine. The maximum values of these parameters, which were significantly higher than the control values, were observed after the healing process had started.
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PMID:Changes in polyamine metabolism of rat liver after administration of D-galactosamine. Favorable effects of putrescine administration on galactosamine-induced hepatic injury. 44 9

Six to 12 hr after IP injection of 400 mg/kg of D-galactosamine in rats a 5-fold increase in plasma insulin was observed. In addition, impaired glucose assimilation was present after an IV Load in spite of unchanged fasting glucose levels. In streptozotocin-diabetic rats (100 mg/kg IV) plasma insulin remained diminished 12 h after induction of D-galactosamine hepatitis. Under identical conditions of preparation and incubation, the liver plasma membranes of D-galactosamine-treated rats, in both normal and diabetic states, bound only 40--60% as much insulin per mg of membrane protein as those of the control rats. Scatchard analysis suggested that this was due to a decrease in the number of receptor sites in the membranes of the D-galactosamine-injected rats. No difference in the insulin degrading capacity and in insulin-receptor dissociation of the plasma membranes between control and D-galactosamine-treated groups was found. These data suggest that a reduction in the number of hepatic insulin receptors in galactosamine hepatitis can lead to insulin resistance and hyperinsulinaemia.
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PMID:Reduced insulin binding to hepatic plasma membranes in D-galactosamine-treated rats. 48 65


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