Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heavy beef heart mitochondria were exposed to controlled concentrations of several volatile anesthetics including halothane, enflurane and chloroform. These anesthetics caused a concentration-dependent release of protein from mitochondria with maximal release occurring at 17.5% halothane and less release at lower and higher concentrations. The proteins released into the supernatants were analyzed by electrophoresis on slab gels containing a 6--20% gradient of acrylamide. The anesthetics caused the release of several polypeptides from mitochondria into the incubation medium; the major polypeptides released had molecular weights of 78 000; 48 000; 47 000; 43 000; 32 000 and 22 000. Two of these were identified by enzyme analysis and by co-electrophoresis with crystalline enzymes as the subunits of aspartate aminotransferase (43 000 daltons; EC 2.6.1.1) and malate dehydrogenase (32 000 daltons; EC 1.1.1.37). Mitochondria exposed to saturated halothane vapors were similar ultrastructurally to controls except that the halothane mitochondria appeared uncoupled. Similar results were obtained with O2 or N2 as carrier gas.
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PMID:Extraction of mitochondrial proteins by volatile anesthetics. 70 81

After a chloroform intraperitoneal injection, lactate dehydrogenase, alanine aminotransferase and particularly aspartate aminotransferase serum activities are much more raised in deficient animals. Liver ornithine decarboxylase (ODC) activity normally decreases in rats between the 4th. and the 7th. month after the weaning. In vitamin A deficient animals, basal values of the enzyme activity are lower and the decrease is deeper. But even at month 7, liver sustains a partial capacity of ODC recovery if retinol is fed during 15 days. Chloroform administration strongly enhances liver ODC activity in normal rats. In the deficiency, stimulation is lower in absolute value but relatively higher if referred to basal level. After retinol refeeding, chloroform stimulates enzyme activity to nearly normal values. Vitamin A deficiency impairs obviously liver ODC activity and its response to chloroform stimulation in rats, but the stroke is at least partially reversible in our conditions. Moreover, deficient animals maintain a non negligible capacity of ODC response under chloroform stimulation.
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PMID:[Toxicity of chloroform and vitamin A status in the rat]. 145 50

Various aliphatic alcohols potentiate the toxicity of a wide range of xenobiotics including several haloalkanes. The present series of experiments were designed to test: (i) whether a single subtoxic dose of alcohol can potentiate CCl4 and CHCl3 hepatoxicity, and (ii) whether this potentiation leads to greater animal lethality. Selected members of a homologous series of straight chain alcohols were chosen for this study. Methanol, ethanol, isopropanol, t-butanol, pentanol, hexanol, octanol, decanol, and eicosanol at equimolar doses (10 mmol/kg) were tested in the present investigation. Each alcohol was administered orally to male Sprague-Dawley rats (175-250 g) 18 hr prior to a single oral administration of CCl4 or CHCl3. Liver injury was assessed by plasma transaminases (alanine aminotransferase, ALT; aspartate aminotransferase, AST) and histopathological examination of liver sections 24 hr after the halomethane treatment. None of these alcohols alone increased plasma ALT or AST significantly, whereas CCl4 or CHCl3 administration to alcohol-treated animals resulted in significant elevation of plasma transaminases. Eicosanol (20-carbon alcohol) did not potentiate the toxicity of either halomethane. Methanol, ethanol, isopropanol, and decanol in combination with CCl4 caused massive liver damage but failed to augment CCl4 lethality. t-Butanol, pentanol, hexanol, and octanol significantly decreased the LD50 of CCl4. The hepatotoxic effects of CHCl3 were potentiated by all of the alcohols and the LD50s were also decreased significantly. On a comparative basis, alcohol-potentiated CHCl3 toxicity was greater than the toxicity of CCl4. These findings indicate that even though halomethane liver injury might be potentiated by alcohols, the underlying mechanisms differ among alcohols since not all alcohols potentiate the lethal effects of these halomethanes.
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PMID:Potentiation of CCl4 and CHCl3 hepatotoxicity and lethality by various alcohols. 225 8

Male Swiss Webster mice (25-30 g) maintained on powdered control diet, or on diets containing chlordecone (CD, 10 ppm), mirex (M, 10 ppm), or phenobarbital (PB, 225 ppm) were used in this study. At these low levels, chlorinated hydrocarbon pesticides are not toxic, they neither affect food or water consumption, nor the body weight of mice. After a 15-day dietary protocol, a single challenge dose of CHCl3 (0.1 ml/kg) was administered intraperitoneally in corn oil vehicle. Liver damage was assessed 24 hours later using serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, histopathology, and lethality. For comparison, serum enzymes were measured in a separate group of mice receiving a high dose of CHCl3 (1.0 ml/kg) alone. None of the dietary treatments alone affected any of the serum transaminases. The serum enzymes were remarkably elevated in the mice treated with CD and CHCl3. A high dose of CHCl3 (1.0 ml/kg) elevated the serum enzymes more than 10-fold over those in the mice fed normal diet receiving only the corn oil vehicle. The histopathology of the liver indicated midzonal necrosis typical of liver injury from CHCl3 and depletion of PAS positive glycogen deposits. These effects were not evident in mice treated with 0.1 ml/kg CHCl3 alone. Additional histological alterations in the livers of the CD + CHCl3 group include the degenerated cells, loss of basophilic staining characteristics, and an increased degree of cytoplasmic vacuolation. The amplification of CHCl3 hepatotoxicity by CD was also reflected by a 4.2-fold increase in lethality determined by 48-hour LD50.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Amplification of chloroform hepatotoxicity and lethality by dietary chlordecone (kepone) in mice. 245 13

The toxicity of several halogenated and non-halogenated hydrocarbons (CH2Cl2, CHCl3, CCl4, C6H14, C8H10) in isolated rat hepatocytes were compared. Release of aspartate aminotransferase (AST) activity was rapid and concentration-dependent. Fractional AST release plateaued at 10-60 min following hydrocarbon exposure. Enzyme leakage at 60 min correlated with the oil/water partition coefficient (pi) of the compounds. All compounds, except n-hexane, also caused an immediate inhibition of the rate of cellular respiration. Inhibition of cell respiration also correlated with pi and was reversible. The recovery of cellular oxygen consumption was examined in detail for CCl4 and correlated with evaporation of the compound. These data suggest that acute hydrocarbon-induced injury in isolated hepatocytes is mediated by concentration-dependent direct solvent effects. Since halogenated hydrocarbons are widely used to induce general anesthesia, the clinical implications of possible direct effects by halocarbons on liver function in vivo and the potential relationship to liver injury are discussed.
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PMID:Rapid halogenated hydrocarbon toxicity in isolated hepatocytes is mediated by direct solvent effects. 362 14

The suitability of isolated rat hepatocytes for the investigation of the toxicity of chemical mixtures has been studied. Cadmium chloride and chloroform were used because both had been previously investigated in hepatocytes and both produce hepatotoxicity after in vivo administration. The addition of the two chemicals caused an increase in cytotoxicity as assessed by loss of intracellular potassium ion and aspartate aminotransferase. There was even a toxic response form the mixture at concentrations where the chemicals alone yielded no such response. The metabolic parameter, lactate to pyruvate ratio, was less consistently affected. The nature of the interaction could, under the varying conditions employed, be described as one of synergism, potentiation, or addition. The data support the proposed role of isolated hepatocytes in screening chemical mixtures for toxic effects.
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PMID:Assessment of the toxicity of chemical mixtures with isolated rat hepatocytes: cadmium and chloroform. 369 18

Carbon tetrachloride (CCl4) added to isolated rat hepatocytes produces toxic effects which were assessed by monitoring the release of aspartate aminotransferase (ASAT). CBrCl3 was equitoxic with CCl4, while CHCl3 was inactive, suggesting solvent properties not to be involved. The CCl4-mediated toxicity was markedly decreased by carbon monoxide, indicating possible activation by cytochrome P 450. 55 flavonoid compounds were tested for their ability to interfere with CCl4-induced release of ASAT. The compounds are cianidanol, 3-ethers and 3-esters thereof, flavanones, flavanolols, flavones and flavanols. The more hydrophilic compounds inhibit the CCl4-induced toxicity, while the lipophilic derivatives are potentiators. No other structure-activity relationships are apparent. The results are discussed in terms of the mechanisms of action of the compounds and of the validity of the technique as a screening test for hepatotropic agents.
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PMID:Inhibiting or potentiating effects of flavonoids on carbon tetrachloride-induced toxicity in isolated rat hepatocytes. 377 62

A pilot study addressed potential effects of long-term exposure to chlorination products in swimming pools. The indicator compound chloroform was detectable in blood from competitive swimmers in an indoor pool (mean = 0.89 +/- 0.34 microgram/l; n = 10), but not in outdoor pool swimmers. No hepatotoxic effect was indicated by serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) or gamma-glutamyl transpeptidase (gamma-GT) enzyme levels. beta-2-microglobulin, an indicator of renal damage, was significantly elevated in urine samples of the slightly, but significantly, younger indoor swimmers. The precise ratio between these 2 possible causes, age and chloroform exposure, as well as the mechanism of the former, remain to be elucidated.
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PMID:Swimming pool chlorination: a health hazard? 791 Dec 64

Chloroform (CHCl3) is widely used in the manufacture of drugs, cosmetics, plastics and cleaning agents. It is also found in chlorinated drinking water. This study was designed to investigate the toxic effect of CHCl3 on isolated male rat hepatocytes using several toxicity parameters. The hepatocytes were isolated by a collagenase perfusion technique and the cell viability was determined by Trypan blue exclusion. The leakage of cytosolic enzymes such as aspartate transaminase (AST) and alanine transaminase (ALT) after treatment with CHCl3 was measured. Reduced glutathione content (GSH) and its related enzymes, glutathione reductase (GSH-Rx) and glutathione peroxidase (GSH-Px), were also evaluated to study the effect of CHCl3 on hepatocytes. Exposure to 100 and 1000 ppm CHCl3 results in a significant decrease in cell after 30 min incubation. However, the effect of 1 and 10 ppm concentrations was observed at 60 min incubation. AST leakage was significantly increased in all treatment groups, while ALT was significantly increased at 100 and 1000 ppm CHCl3 after 60 and 30 min, respectively. As early as 15 min, GSH was decreased significantly at 1000 ppm, but at 100 and 10 ppm CHCl3 the decrease in GSH began after 30 and 120 min, respectively. GSH-Px activity did not changed. However, the activity of GSH-Rx was significantly decreased at 1000 ppm CHCl3 and at the same time GSH content was decreased. The data indicate that the toxic effect of CHCl3 was dose- and time-dependent. The degree of GSH depletion correlated with increased cytotoxicity and decreased GSH-Rx activity due to CHCl3.
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PMID:The mechanism of chloroform toxicity in isolated rat hepatocytes. 835 69

The hepatoprotective effect of various fractions (n-hexane, CHCl3, EtOAc, n-BuOH, and H2O) of Ban-zhi-lian derived from Scutellaria rivularis Benth was studied against carbon tetrachloride (CCl4), D-galactosamine (D-GalN) and acetaminophen (APAP)-induced acute hepatotoxicity in rats. Liver damage was assessed by quantifying serum activities of glutamate oxaloacetate transaminase (sGOT) and glutamate pyruvate transaminase (sGPT), as well as by histopathological examination. The results indicated that the CHCl3 fraction and EtOAc fractions exhibited the greatest hepatoprotective effects on CCl4-induced liver injuries, the CHCl3 fraction and n-hexane fraction are most potent against D-GalN-induced intoxication, and the CHCl3 fraction represented the most liver-protective effect on APAP-induced hepatotoxicity. The pathological changes of hepatic lesions caused by these three hepatotoxicants were improved by treatment with the fractions mentioned above, which were compared to Glycyrrhizin (GLZ) and Silymarin as standard reference medicines.
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PMID:Hepatoprotective effect of the fractions of Ban-zhi-lian on experimental liver injuries in rats. 920 8


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