Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of a nucleoside-nucleotide mixture on liver injury of rats induced by D-galactosamine was studied by examining changes in function and histopathology of the liver. Animals with liver damage received total parenteral nutrition with glucose and amino acids supplemented with a nucleoside-nucleotide mixture containing inosine, cytidine, GMP, uridine and thymidine, or with uridine which inhibits galactosamine injury, or with liver cell extract containing flavin adenine dinucleotide and nucleic acid derivatives. As control, animals with liver damage received total parenteral nutrition with glucose and amino acids only. The serum GOT and GPT concentrations were significantly lower in the group supplemented with nucleoside-nucleotide mixture than those in other groups. A large dose (1.2 g/kg) of uridine inhibited liver injury, but a lower dose (0.14 g/kg) did not have any effect, whereas nucleoside-nucleotide mixture containing the same amount of uridine inhibited the injury. Liver cell extract also did not improve liver function. Thus infusion of a physiological and balanced mixture of nucleosides or nucleotides may improve liver function in rats with liver injury.
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PMID:Effects of total parenteral nutrition with nucleoside and nucleotide mixture on D-galactosamine-induced liver injury in rats. 312 56

Tumor necrosis factor (TNF) has been shown to mediate lipopolysaccharide-induced neutrophil adhesion to liver sinusoidal endothelium in vivo. Female NMRI mice received either 5 micrograms lipopolysaccharide (R595) per animal alone (model A) or together with 116 mumol D-galactosamine (model B). One hour after injection, TNF activity in the serum was detectable to an equal extent in both models. Neutrophils in the liver, which had been identified by chloroacetate esterase staining of liver sections and quantitated by light microscopy, started to increase at 1 h and were elevated 10-fold above baseline at 6 h after application in (A) and (B). If 0.5 micrograms TNF instead of lipopolysaccharide was injected alone (model C) or together with D-galactosamine (model D), neutrophil influx into the liver was comparable to that observed in (A) or (B). Alanine aminotransferase activity in the serum was nearly normal in (A) and (C) 6 h after injection, while it reached levels up to 50-fold above baseline in models (B) and (D). This reflects the well-known D-galactosamine sensitization against lipopolysaccharide or TNF. Furthermore, degranulation of a large number of intrasinusoidal neutrophils could be observed 9 h after lipopolysaccharide-galactosamine injection. The administration of 116 mumol D-galactosamine per animal alone led neither to a measurable TNF activity in the serum nor to an increase in alanine aminotransferase activity or number of liver neutrophils. If the animals had received 50 microliter turpentine subcutaneously 24 h prior to lipopolysaccharide, TNF or D-galactosamine injection, the induced acute-phase reaction suppressed the increase of liver neutrophils in all models. Acute-phase reaction also prevented neutrophil degranulation and the rise of alanine aminotransferase in (B) to a great extent, while serum TNF activity was only minimally affected. It is concluded that TNF mediates neutrophil adhesion to the sinusoidal endothelium in vivo and that acute-phase reactants prevent lipopolysaccharide- or TNF-induced neutrophil influx into the liver.
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PMID:Involvement of tumor necrosis factor in endotoxin-triggered neutrophil adherence to sinusoidal endothelial cells of mouse liver and its modulation in acute phase. 319 26

Reductive metabolism of halothane was measured after acute liver injury induced by galactosamine (1.0 g/kg, IP) in rats. On the seventh day of liver injury, when previously elevated serum alanine aminotransferase levels had returned to near normal range, anaerobic release of fluoride from halothane by hepatic microsomes, which appears to reflect the reductive pathway of halothane metabolism, was still remarkably decreased (1.36 +/- 0.56 nmol/mg protein/h vs 5.88 +/- 0.58 in controls, P less than 0.001). In another set of experiments, rats (n = 8) given galactosamine 7 days earlier and saline-treated control rats were given halothane anesthesia (1.0%) under mildly hypoxic conditions (F1O2 0.14). In saline controls, halothane anesthesia resulted in a mild but statistically significant increase in serum alanine aminotransferase levels (32 +/- 4 vs 59 +/- 6 U/ml, P less than 0.001). In contrast, serum levels of this enzyme were not changed by halothane anesthesia in galactosamine-treated rats (45 +/- 3 vs 49 +/- 4 U/ml). Although care should be taken in extrapolating the importance of these animal data to humans, the results of this study suggest that halothane hepatotoxicity can be attenuated in the presence of minor liver injury as a result of decreased hepatic biotransformation of the anesthetic. The data support the view that halothane anesthesia is not necessarily contraindicated in subjects with impaired liver function.
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PMID:Halothane hepatotoxicity and reductive metabolism of halothane in acute experimental liver injury in rats. 336 63

Serum proteolytic activity was determined in galactosamine-treated rats and in controls. Injection of the hepatotoxin at a dose of 400 mg/kg resulted in a 3.4-fold elevation in the serum proteolytic activity, while AST (aspartate aminotransferase), ALT (alanine aminotransferase) and bilirubin were increased by factors of 3.9, 8.8 and 4.5, respectively. Studies with proteinase inhibitors revealed that the serum proteolytic activity was partially metal-dependent as well as puromycin and antipain sensitive. Differences in susceptibility to a combination of N-ethylmaleimide and antipain indicated presence of different proteolytic systems in the sera of liver damaged and control rats. Separation of serum proteinases by gel filtration showed that the galactosamine-intoxicated rat serum contained activity which did not appear in the control serum. This activity was partially metal dependent, antipain and N-ethylmaleimide sensitive, and was more susceptible to dithiothreitol than the control activity. These findings demonstrate that hepatocellular damage induced by galactosamine caused not only an increase in serum proteinases, but was also associated with the appearance of enzymes not normally released by the liver of untreated animals.
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PMID:Quantitative and qualitative changes of serum proteolytic activity in rats with liver damage induced by galactosamine. 353 Jan 92

Tritoqualine (TRQ) was previously reported to suppress enzyme leakage and lipid peroxidation induced by carbon tetrachloride in isolated hepatocytes. In the present study, we investigated the effect of TRQ on enzyme leakage from rat primary-cultured hepatocytes using D-galactosamine (GalN) which causes hepatic injury without lipid peroxidation. Leakage of GPT and GPT was significantly increased at 18 hr after GalN addition, being saturated at 42-50 hr. This enzyme leakage was suppressed dose-dependently by TRQ at 42 hr, but not by vitamin E. These results suggest that TRQ shows a suppressive effect on enzyme leakage from hepatocytes independently of its inhibitory action on lipid peroxidation.
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PMID:Suppressive effect of tritoqualine on enzyme leakage induced by D-galactosamine in rat primary-cultured hepatocytes. 358 15

Although copper is believed to be hepatotoxic in Wilson's disease and Indian Childhood Cirrhosis (ICC), the rat shows only minimal hepatic damage on copper-loading. To investigate the possibility that copper deposition may potentiate the effects of a superimposed hepatitis, D-galactosamine (GalN) was given to copper-loaded and control rats. In the non-copper-dosed rats, GalN 0.85 g/kg i.p. produced elevated serum AST (3731 +/- 545 IU/l; normal 64.8 +/- 2.1), ALT (2090 +/- 190 IU/l; normal 18.0 +/- 0.7), and OCT (16.7 +/- 2.6 mmol/min/ml; normal 0.12 +/- 0), and liver cell necrosis with portal infiltration. In rats whose liver copper was elevated to 1298 +/- 169 micrograms/g (control 18.7 +/- 1.7) by oral copper supplementation, GalN produced much smaller increases in AST (825 +/- 122 IU/l), ALT (103 +/- 15 IU/l) and OCT (0.27 +/- 0.02 mmol/min/ml) and minimal histological damage. Viable bacterial cell counts from faecal homogenates showed that the anaerobically cultured bacteria were reduced on copper-dosing of rats. Therefore the protective effect of copper may be due to a decrease in gut-derived endotoxin acting on the liver, or to an impaired prostaglandin synthesis or perhaps to synthesis of acute phase reactants.
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PMID:Copper protects against galactosamine-induced hepatitis. 365 8

Two strains of mice (C57BL/10ScN and C3H/HeJ) that carry the same mutant lipopolysaccharide gene (Lpsd) which makes them resistant to the toxic effects of endotoxin (LPS) are also partially resistant to the hepatotoxic effects of D-galactosamine. As measured by serum alanine aminotransferase, the degree of liver injury induced by D-galactosamine in the LPS-resistant strains is only 10%-30% that of closely related strains of LPS-sensitive mice. Similarly, histopathologic changes are less pronounced in the endotoxin-resistant strains than in LPS-susceptible mice. By transferring spleen cells from LPS-susceptible strains to lethally irradiated, LPS-resistant mice, we established that susceptibility to D-galactosamine is mediated by lymphoreticular cells. Radiation-resistant spleen cells transferred D-galactosamine sensitivity, suggesting a role for macrophages. We did not exclude the possibility that lymphocytes can also transfer the response to D-galactosamine. These results establish that in mice, D-galactosamine sensitivity is associated with endotoxin sensitivity and that the former is mediated by lymphoreticular cells, not by hepatocytes.
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PMID:D-Galactosamine hepatotoxicity is associated with endotoxin sensitivity and mediated by lymphoreticular cells in mice. 388 May 54

The effect of D-galactosamine on the structure of the glycan moiety of alpha 1-acid glycoprotein was studied throughout a nine days experiment. It was shown that: D-galactosamine led to an alteration of the Concanavalin A crossed immunoelectrophoresis pattern and to a decreased sialic acid content of alpha 1-acid glycoprotein. The undersialylation of alpha 1-acid glycoprotein was not linked to a change in the relative ratio of various Concanavalin A forms. At the end of the experiment (9 days after galactosamine injection), the Concanavalin A non-reactive forms of alpha 1-acid glycoprotein remained elevated whereas alanine transaminase activity, total protein and alpha-acid glycoprotein had returned to a control level. D-galactosamine-treated rats seem to be a suitable model for the study of the very fast cyclic modulations of the synthesis of the glycan moiety of glycoproteins.
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PMID:D-galactosamine-induced liver injury: a rat model to study the heterogeneity of the oligosaccharide chains of alpha 1-acid glycoprotein. 400 35

The antihepatotoxic effects of tannin analogues were examined utilizing carbon tetrachloride- and galactosamine-induced cytotoxicity in primary cultured rat hepatocytes. Most tannins showed significant antihepatotoxic effects in these two assay systems. Hydrolyzable tannins generally exhibited an intense enzyme inhibitory action on glutamic-pyruvic transaminase while condensed tannins exerted a much less inhibitory action, although variations were observed depending on structure. Structure-activity relationships are discussed.
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PMID:Antihepatotoxic actions of tannins. 408 19

1. In confirmation of previous work, administration of d(+)-galactosamine (0.5-0.75g/kg body wt.) to rats caused a hepatitis with histological evidence of liver damage and a 9-fold rise in aspartate aminotransferase activity in serum. 2. There was a significant elevation of blood lactate and pyruvate concentrations in 24h-starved rats treated with galactosamine but no change in the [lactate]/[pyruvate] ratio. 3-Hydroxybutyrate and acetoacetate concentrations in blood were decreased. 3. The changes in the concentrations of lactate, pyruvate and ketone bodies in the freeze-clamped liver were parallel to those observed in the blood. 4. In the livers of 24h-starved galactosamine-treated rats there were large increases in the concentrations of alanine (3-fold), citrate (5-fold), 2-oxoglutarate (4-fold), with smaller increases in malate, glutamate and aspartate. There was a 4-fold rise in the value of the mass-action ratio of the alanine aminotransferase system in the livers of galactosamine-treated rats when compared to controls. 5. There was a significant decrease in the activities of aspartate and alanine aminotransferases in the cytoplasm and the soluble fraction of sonicated homogenates of the livers of rats treated with galactosamine. The activity of phosphoenolpyruvate carboxylase was decreased by 75% of the control value. 6. Glucose synthesis from lactate in perfused livers from galactosamine-treated rats was inhibited 39% when compared with controls. 7. The results indicate that the conversion of lactate into glucose is decreased in the livers of galactosamine-treated rats and that this decrease may be due to the loss of phosphoenolpyruvate carboxylase from damaged hepatocytes.
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PMID:Metabolic studies in experimental liver disease resulting from D(+)-galactosamine administration. 465 44


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