Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Local inflammation evoked in Swiss albino mice by subcutaneous injection of Celite resulted in a rise of liver tyrosine aminotransferase activity and plasma level of fibrinogen and seromucoid, while liver alanine aminotransferase activity and plasma level of fibrinogen and seromucoid, while liver alanine aminotransferase activity and the plasma level of albumin and total protein remained unaltered. By measuring the incorporation of [14C] leucine, stimulation of liver and plasms protein synthesis by Celite injection was demonstrated. Administration of D-galactosamine (2-5 mg/10 g body weight) inhibited the enhanced synthesis of liver proteins, and especially of trauma-induced synthesis of plasma fibrinogen and seromucoid. The inhibitory effect of galactosamine was most pronounced when the amino sugar was injected simultaneously with Celite and then protein synthesis was measured 6 h later. The results obtained support the idea that high doses of galactosamine inhibit transcription of trauma-inducible mRNA in the liver and thus block the acute-phase response.
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PMID:Inhibition of the liver and plasma protein acute-phase response in mice by D-galactosamine. 1 81

The protective action of aspartic acid on isolated and perfused rat liver was studied. In case of D-galactosamine intoxication the GOT, GPT and SDH activity and the lactate and pyruvate concentration in the perfusion medium were less augmented and the glycogen level in hepatic tissue was less diminished in animals treated with aspartic acid, as compared to controls. The histochemical applied (PAS reaction for glycogen, nucleic acids, NADH2-diaphorase, glucose-6-phosphatase and membrane-ATP-ase), also stated a protecting effect in the treated animals. The protective action of aspartate is hypothetically considered to be exerted by its capacity to reestablish the cellular deficit of pyridine nucleotides and thus to improve the synthesis of nucleic acids, glycoprotein and glycolipids or/and by its participation in various metabolic pathways.
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PMID:Protecting action of aspartate on the hepatic changes induced by D-galactosamine. 18 87

The hepatotoxic effects of carbon tetrachloride (0.01 ml/kg i.p.), thioacetamide (50 mg/kg intraperitoneally), paracetamol (0.5 g/kg intraperitoneally), and allyl alcohol (0.05 ml/kg intraperitoneally) as estimated by determination of serum enzyme activities (GOT, GPT, SDH) were enhanced in mice treated with one oral dose of 4.8 g/kg ethanol 16 hrs. previously. Pretreatment of mice with ethanol did not increase the hepatotoxic actions of bromobenzene (0.25 ml/kg intraperitoneally), phalloidin (1.5 mg/kg intraperitoneally), alpha-amanitin (0.75 mg/kg intraperitoneally), and praseodymium (12 mg/kg intravenously) though there was a trend to higher enzyme activities in the case of bromobenzene. In guinea-pigs ethanol also aggravated CCl4-induced liver damage, but only strengthened the hepatotoxic activity of D-galactosamine (150 mg/kg intraperitoneally). Treatment with 4.8 g/kg ethanol did not influence liver glutathione levels in mice but increased aniline hydroxylation in the 9000 x g liver homogenate supernatant of mice and guinea-pigs. A dose of 2.4 g/kg ethanol, on the other hand, neither increased aniline hydroxylase activity nor enhanced carbon tetrachloride-induced hepatotoxicity in mice. It is assumed that the enhanced sensitivity to hepatotoxic agents after treatment with ethanol may be due to an enhanced microsomal activation of these substances.
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PMID:The influence of ethanol pretreatment on the effects of nine hepatotoxic agents. 56 75

The morphological and biochemical studies were performed on the injured livers of female rats produced by chronic administration of D-galactosamine (GALN) (250 mg/kg, i.p.) for 7 months. Light microscopically, cirrhotic changes were observed in most of the animals characterized by the proliferation of the connective tissues from portal triads into hepatic lobules. The electron microscopic study demonstrated mitochondrial proliferation and irregularities with crenated membranes, focal hypertrophy of the smooth endoplasmic reticulum, decrease of the rough endoplasmic reticulum with partial detouchment of ribosomes, slight loss of compactness of nucleoli and no remarkable accumulation of lipid droplets in the cytoplasm. The proliferation of collagen fibers was observed around the hepatocytes and acid mucopolysaccharides were seen in the space of Disse and partly in the sinusoids histochemically using electron microscope. Biochemically chronic GALN administration, which increased hepatic weight significantly, resulted in a significant decrease in microsomal protein concentration, whereas cytochrome P450 content significantly increased. There was no change in phospholipid contents. After GALN, plasma albumin concentration was significantly decreased and the value of zinc turbidity test was increased. However, there was no change in plasma GPT level and total cholesterol concentration.
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PMID:D-galactosamine induced hepatic cirrhosis: its ultrastructural and biochemical studies in rat. 65 50

A number of amide derivatives of maleopimaric acid were synthesised and preliminary results on their protective activity against galactosamine-induced liver damage in the rat are described. The compounds (2, 6, 9 and 15) were found to display the highest level of protective activity producing significant lowering of serum GOT and GPT levels at a daily dose of 250-300 mg/kg. The LD50 of these compounds was typically in excess of 2000 mg/kg.
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PMID:New hepato-protective agents. I. Maleopimaric acid-4alpha-carboxamides. 103 71

An experimental hepatitis was induced in rabbits by intravenous infusion of 1 g galactosamine per kilogram of body weight. Galactosamine administration caused microclot formation in kidneys, liver, lungs, and spleen in a low percentage. If, however, animals were infused with the fibrinolysis inhibitor epsilon-aminocaproic acid in addition to galactosamine, microclots were generated in a high percentage. The microclots exhibited typical staining characteristics like those observed in the generalized Shwartzman reaction. Some animals developed bilateral renal cortical necrosis. Heparin treatment prevented the occurrence of microclot fromation after galactosamine administration, but it neither prolonged the survival time of the animals nor prevented or reduced liver cell damage. Increases in serum GPT and bilirubin levels were similar in heparin-treated and untreated rabbits. The experiments indicate that disseminated intravascular coagulation is involved in galactosamine-induced hepatitis but does not contribute to the severity of the liver injury.
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PMID:Experimental galactosamine-induced hepatitis. Effect of anticoagulant and antifibrinolytic agents on microclot formation. 125 92

In previous studies, we reported that the age-dependent hepatotoxicity of galactosamine (GalN) was evident in hepatocytes maintained in primary cultures. Cellular proliferation and tissue repair are not manifested in response to injury in this in vitro system. Neonatal (5-day) rats have ongoing hepatocellular proliferation in contrast to adult (5-month) rats, and should be therefore resilient to GalN toxicity. Liver injury was assessed by serum transaminases (ALT, AST), 3H-thymidine (3H-T) incorporation into nuclear DNA, and content of hepatocellular nuclear DNA. While the dose of 400 mg/kg did not cause any significant liver injury in the neonates, it did produce significant liver injury in adult rats. At a dose of 800 mg/kg, GalN produced significant injury in the neonates. Because 400 mg/kg causes clearly demonstrable liver injury in the adult and no injury in the neonates, this dose was used for further studies. In addition to the above measures of injury, uracil nucleotides (UTP, UDP, and UMP), glycogen, histopathology, and autoradiographic examination of liver sections were used to assess the liver injury in neonatal and adult rats. In a time-course study, all of the above were measured at 0, 12, 24, 36, 48 and 72 h after GalN administration. Serum enzyme elevations as well as the appearance of necrotic and swollen hepatocytes were maximal at 24 h in the adults rats. In contrast to these observations in the adult rats, none of these measurements indicated significant liver injury in the neonates. 3H-T incorporation into nuclear DNA was much higher in the neonatal liver in comparison to the adults reflecting the difference in regeneration. Hepatocellular nuclear DNA was also higher in the neonate and was significantly decreased due to GalN treatment. In the adult rats, the quiescent normal level of 3H-T incorporation and nuclear DNA content were further decreased at 12 h, increased at 48 h and returned to normal low, quiescent levels at 72 h. In the neonates mitotic activity of hepatocytes was higher than in the adult rats. In the adult rats, mitotic activity was increased at 48 h after GalN administration and returned to normal at 72 h. In the neonates GalN did not alter the mitotic activity significantly. These findings demonstrate that in the presence of hepatocellular regeneration, galactosamine toxicity is minimal while in the absence of it, clear toxicity is manifested. In conclusion, while perturbation in uracil nucleotides and related biochemical events may explain the infliction of liver injury by GalN in an age-dependent fashion, the extent of tissue repair impacts decisively on the final outcome of injury.
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PMID:Ongoing hepatocellular regeneration and resiliency toward galactosamine hepatotoxicity. 129 Apr 5

The effects of d-catechin (d-CTC) on carbon tetrachloride- and d-galactosamine (d-Ga1N)-induced cytotoxicity in primary cultured rat hepatocytes were examined. After 1.5 h preincubation, d-CTC was added at doses of 0.1-5.0 mg/ml to culture medium together with 10 mmol/L CCl4 or 5 mmol/L d-GalN, respectively. GOT, GPT and LDH levels were measured 1.5 h after treatment. The results showed that d-CTC at doses of 0.6 to 5.0 mg/ml could protect the hepatocytes against the toxic effects of CCl4 and d-GalN. At the higher doses (2.5-5.0 mg/ml), d-CTC showed weak inhibition of LDH and GPT activities, but these did not influence its anti-hepatotoxic activity.
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PMID:[Effect of d-catechin on carbon tetrachloride- and d-galactosamine-induced cytotoxicity in primary cultured rat hepatocytes]. 139 38

The saponins (ASI, SK) used in this study was extracted from the root of Astragalus membranaceous Bge and Astragalus sieversianus Pull. ASI and SK were found to protect liver from chemical injury induced by CCl4, D-galactosamine and acetaminophen in mice. The two saponins were shown to impede the elevation of SGPT level, decrease the MDA content and increase the GSH concentration in mouse liver. Obvious improvement of histological changes were also observed. The protective action of ASI and SK against the hepatotoxicity was also shown in experiments using primary cultured rat hepatocytes. The average value of GPT in the medium treated with different concentration of ASI and SK (0.00075-0.18 mmol/L) was lower than that in control. Analyzing through multiple linear correlation, we showed that the lowering of SGPT was negatively related to the increase of GSH, positively related to the decrease of MDA in mice given CCl4 or acetaminophen in combination with ASI or SK. These results indicate that the hepato-protective effects of ASI and SK may be due to their anti-oxidation activities, since the content of liver protein in mice given ASI or SK was more than that in the controls. Moreover, the level of hepatic microsomal cytochrome P-450 in all mice given the two saponins were significantly increased, the liver metabolism and immunoregulating action produced by ASI and SK may be also involved in their hepato-protective effects.
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PMID:[Effects of astragalus (ASI, SK) on experimental liver injury]. 144 65

The effects of the epimeric glycyrrhizic acids (GA), 18 alpha-form and 18 beta-form, on D-galactosamine (Gal)-induced acute liver injury and fulminating hepatic failure (FHF) in rats were studied. In rats of acute liver injury, extensive liver parenchymal cell damage was observed by the elevation of alanine aminotransferase (ALT) activity and confirmed by significant histopathological changes 24 and 48 h after ip Gal 450 mg.kg-1. Moreover, marked elevation in the liver putrescine levels occurred along with that of serum ALT. The spermidine and spermine levels did not alter significantly. GA 18 alpha-form 300 mg.kg-1 ip suppressed the elevation of serum ALT and liver putrescine levels, and improved all the histopathologic features. On the other hand, GA 18 beta-form 300 mg.kg-1, which exhibited inhibitory effects 24 h after ip Gal, showed no action 48 h after ip Gal. The ALT levels in the serum from GA 18 alpha-form, 18 beta-form, vs control groups after 24 h were 70 +/- 24 (P < 0.01) and 78 +/- 42 (P < 0.01) vs 155 +/- 57, and after 48 h were 74 +/- 25 (P < 0.01) and 258 +/- 99 (P > 0.05) vs 293 +/- 110. The putrescine contents (nmol.g-1) in the liver from GA 18 alpha-form, 18 beta-form, vs control after 24 h were 34 +/- 9 (P < 0.01) and 51 +/- 12 (P < 0.01) vs 139 +/- 29, and after 48 h were 16 +/- 3 (P < 0.01) and 150 +/- 11 (P > 0.05) vs 156 +/- 23.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Therapeutic effects of epimeric glycyrrhizic acids on hepatic injury in rats]. 145 65


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