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)

Activity of alanine and aspartate aminotransferase, alkaline phosphatase, adenosine, desaminase and AMP-aminohydrolase was determined in rats in the process of the liver regeneration under acute and chronic lesion with CCl4. It is shown that under chronic lesion of the liver with CCl4, in contrast to the acute one, changes in the aminotransferase activity in blood serum are not expressed in the liver, the activity is essentially decreased. A steady increase was observed in the activity of adenosine desaminase, AMP-aminohydrolase and alkaline phosphatase in the liver and blood serum. It is concluded that the normal regenerative process is accompanied by short-term shifts of the enzymes activity in the liver and blood serum. The development of a chronic process results in a characteristic increase in the activity of adenosine desaminase, AMP-aminohydrolase and alkaline phosphatase in the liver and blood serum.
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PMID:[Enzyme activity during regeneration under acute and chronic liver lesion with CCL4]. 68 74

Rate of incorporation of 1-14C-glycine in total protein and subcellular fractions of rat liver tissue as well as the activity of alanine- and aspartate aminotransferases in blood serum were studied at various periods after treatment with CCl4. The protein synthesis was distinctly decreased in liver tissue and the alanine aminotransferase activity was markedly increased in blood serum with the first days after CCl4 administration. Dissimilar alterations were observed in the rate of the label incorporation into nuclear and mitochondrial fractions after prolonged administration of CCl4. Hepatocyte nuclei proved to be more sensitive to cytoplasmic alterations caused by tetrachlormethane. Incorporation of 1-14C-glycine into both nuclear and mitochondrial fractions was decreased only at later periods. In blood serum the alanine aminotransferase activity was drastically increased after prolonged administration of CCl4, whereas the aspartate aminotransferase activity was increased as compared with control less markedly.
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PMID:[Incorporation of 1-14C-glycine into total protein and subcellular fractions of rat liver at different periods following administration of tetrachlormethane]. 85 28

The influence of bovine somatotropin in acute CCl4 poisoning was studied in rabbits. Somatotropin was injected subcutaneously in doses of 2.5 mg/kg. Liver damage was assessed on the basis of alanine and aspartate aminotransferase and aldolase activities. STH injected during 10 experimental days or 5 days preceding experimental poisoning with CCl4 did not increase the degree of liver damage in comparison with the group of animals injected only with carbon tetrachloride.
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PMID:Influence of bovine somatotropin on the liver experimentally damaged with carbon tetrachloride. 116 53

Liver damage induced in rats by carbon tetrachloride (CCL4) was obvious macroscopically as well as microscopically in stained sections. Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transpeptidase (gamma-GT) were also significantly raised. Adenosine and inosine effectively countered the damage when these were given before and during the period during which CCl4 produces the typical damage. The beneficial effect was seen in biochemical as well as pathological studies.
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PMID:Effect of adenosine and inosine on carbon tetrachloride-induced liver damage in rats. 135 Jul 72

The possible aggravation of liver injury by impaired cellular antioxidant function was investigated. A vitamin E-deficient diet (0.5 mg/kg alpha-tocopherol; control 100 mg/kg) significantly reduced rat liver alpha-tocopherol concentrations after 4 weeks (1.8 +/- 1.7 micrograms/g; control 34.4 +/- 2.4 micrograms/g, p < 0.001). The effects of copper loading (Cu, 3 g/kg diet); galactosamine (GalN, 0.85 g/kg i.p.); or carbon tetrachloride (CCl4, 10 mmol/kg i.p.) were examined. Serum aspartate transaminase activity was elevated slightly by vitamin E deficiency but not by hepatic copper accumulation. In vitamin E-replete (E+) and vitamin E-deficient (E-) rats, GalN or CCl4 caused a large and comparable elevation in serum AST and OCT activity. This effect on AST was markedly reduced by copper loading in vitamin E replete (E+) rats, but in E(-) rats copper had significantly less protective effect. Copper also diminished the OCT response to GalN in E+, though not E-, rats. A significant rise in total hepatic alpha-tocopherol content followed administration of GalN or CCl4 in both normocupric and copper-laden E(-) rats. Thus alpha-tocopherol deficiency (a) was not hepatotoxic per se; (b) failed to potentiate the toxicity of copper, GalN or CCL4; but (c) partially abolished the protection by copper against toxin-induced liver injury. Retention of hepatic alpha-tocopherol after liver damage may partly explain low serum vitamin E levels seen in clinical liver disease.
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PMID:Alpha-tocopherol deficiency fails to aggravate toxic liver injury but liver injury causes alpha-tocopherol retention. 148 10

Female Wistar rats were pretreated with I ml of carbon tetrachloride/kg of body weight or with olive oil. All the rats were given this dose of CCl4 20 or 40 days later. Liver regeneration as evaluated by 3H-thymidine incorporation into liver DNA and by the number of mitotic hepatocytes was markedly impaired in CCl4-pretreated rats when compared with olive oil-pretreated controls. DNA labelling reached only 83 and 59% and mitotic index 35 and 58% of control values, respectively, at 20-day and 40-day time intervals. The variables characteristic of liver damage did not parallel the changes in cell division. About 20% of hepatocytes were necrotic both in the CCl4-pretreated and in the control rats. The activity of serum alanine aminotransferase was higher in the CCl4-pretreated rats. Only serum aspartate aminotransferase activities were somewhat lower when compared to controls. Similarly, serum aminotransferases were much less affected by the pretreatment than the markers of regeneration when two low doses of CCl4 (0.125 ml/kg) were given to rats 20 days apart. The activities of microsomal enzymes aniline hydroxylase and pethidine demethylase were equal in control and in experimental rats 20 days after CCl4 pretreatment which indicated that the effects of CCl4 were not mediated by an overall decrease in cytochrome P-450 enzymes. In summary, a single pretreatment of rats with CCl4 induced changes in liver that lasted for 40 days and impaired liver regeneration when another dose of CCl4 was applied.
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PMID:Prolonged reduction of hepatocyte proliferative ability in rats after a single treatment with carbon tetrachloride. 157 74

Gerbils are much more sensitive to the hepatotoxic and lethal effects of CCl4 than rats as indicated by 48-hr LD50 values (0.08 vs 2.8 ml/kg). On the other hand, gerbils are refractory to chlordecone (CD) potentiation of CCl4 toxicity. To investigate the possible mechanism underlying the high sensitivity of gerbils to CCl4 lethality, the metabolism of CCl4 was studied in gerbils pretreated with dietary CD, phenobarbital (PB), or mirex (M) at 10, 225, and 10 ppm, respectively. The hepatic content of 14CCl4, the expiration of 14CCl4 and 14CCl4-derived 14CO2, and lipid peroxidation were measured and the results were compared with the previous data for rats. After the 15-day dietary pretreatment, male gerbils (60-80 g) received 14CCl4 (0.08 ml/kg; sp act 0.04 mCi/mmol) ip in corn oil and the radioactivity present in the expired air was collected for 6 hr. More than 80% of the parent compound as represented by the 14C-label in the toluene trap was expired in 6 hr regardless of the pretreatments. Expiration of 14CO2 measured during the 6 hr after 14CCl4 administration in control gerbils was 3.5-fold more than that in rats and was significantly increased in pretreated groups (M greater than PB greater than CD). PB and M pretreatments resulted in a significant increase of 14C-label bound to the nonlipid fraction of the liver as compared with CD-treated or control gerbils. The radiolabel present in the livers of control gerbils was 5-fold higher than that of rats. In vivo lipid peroxidation measured as diene conjugation in lipid extracts from the livers was lower in gerbils than in rats, and none of the pretreatments significantly affected lipid peroxidation. The serum alanine aminotransferase and aspartate aminotransferase were significantly elevated at 6 hr after CCl4 injection in all groups of gerbils. These data indicate that the more extensive metabolism of CCl4, as represented by 14CO2 formation and 14C-label bound to hepatic tissue, in gerbils as compared with rats, may partially explain the high sensitivity of gerbils to CCl4 toxicity. However, the enhanced metabolism of CCl4 found in CD-, PB-, or M-pretreated gerbils did not lead to amplified hepatotoxic and lethal effects of CCl4. The reason gerbils may be refractory to CD amplification of CCl4 injury might be associated with other factors yet to be investigated.
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PMID:Lethal effects of CCl4 and its metabolism by Mongolian gerbils pretreated with chlordecone, phenobarbital, or mirex. 169 56

Chlordecone (CD) pretreatment is well known to greatly potentiate CCl4 toxicity. Previous work has shown that suppression of hepatocellular regeneration permits an ordinarily limited liver injury to progress in an irreversible manner. Insufficient hepatocellular energy has been proposed as a mechanism for suppressed hepatocellular regeneration. Since cyanidanol reportedly increases cellular ATP, this compound was employed to test the above hypothesis. The present study was designed to investigate the sequential biochemical and histological changes over a time course of 120 hr after CCl4 administration. Male Sprague-Dawley rats (125-150 g) were maintained on 10 ppm CD diet for 15 days and were challenged with either a standard protocol dose (100 microliters/kg) or a low (50 microliters/kg, L) dose of CCl4. Cyanidanol pretreatment at 48, 24, and 2 hr before CCl4 administration to rats maintained on CD diet resulted in 100 or 70% animal survival, for CCl4 (L) or the standard dose of CCl4, respectively. Preliminary studies indicated that neither simultaneous nor subsequent administration of cyanidanol with CCl4 challenge affords such protection. Prior treatment with cyanidanol and a latency period were found necessary for protection. Without cyanidanol, CD + CCl4 combination caused 50 and 100% lethality after CCl4 (L) and the standard dose, respectively, while the same doses of CCl4 alone did not cause lethal effects. Plasma enzymes (alanine aminotransferase, aspartate aminotransferase, sorbitol dehydrogenase) in control rats showed only moderate and transient increases after CCl4 challenge. The combination of CD + standard dose of CCl4 resulted in progressive and marked elevations of all three serum enzymes at all time intervals until the death of animals. Cyanidanol pretreatment resulted in significant decline in the plasma enzyme elevations at later time points. Cyanidanol pretreatment increased hepatic ATP synthesis in control or CD rats. CCl4 administration to control rats did not alter hepatic ATP levels, while in CD-fed rats hepatic ATP levels were significantly decreased. Cyanidanol pretreatment to CD + CCl4 combination-treated rats did not significantly prevent the decline in hepatic ATP and glycogen levels. However, in the surviving rats a recovery in these parameters was observed. Light microscopic examination of livers from animals that received CCl4 alone revealed only marginal cellular injury, at early time points only. However, CCl4 challenge to rats maintained on CD resulted in progressive injury, characterized by the appearance of ballooned cells, necrotic cells, and cells with lipid droplets in the liver. Cyanidanol pretreatment to these rats caused decreased vacuolation and significantly reduced the progression of liver necrosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Protection from chlordecone-amplified carbon tetrachloride toxicity by cyanidanol: biochemical and histological studies. 170 39

A number of toxic chemicals affect the biliary excretory function of liver. Organochlorines and halomethanes are known to enhance bile flow. Despite the demonstration that a diversity of agents modify biliary function, the mechanism by which these chemicals manifest this effect is not fully understood. This study was designed to assess the effect of colchicine (0.1, 1.0, or 2.5 mg/kg, i.p., in saline) administration on biliary excretory function 6 and 24 hr later. Additionally, the effect of colchicine (1 mg/kg, i.p. in saline) pretreatment in rats 2 hr prior to the administration of a single low dose of CCl4 (100 microL/kg, i.p., in corn oil) or corn oil alone (1 mL/kg, i.p.) on hepatic biliary excretory function was also assessed at 6 and 24 hr after the last treatment. The hepatotoxicity was evaluated by serum enzymes, alanine and aspartate aminotransferases, and histopathological alterations of the liver. Biliary excretion of intravenously administered phenolphthalein glucuronide (PG) was assessed in bile duct cannulated anesthetized rats. Only the highest dose of colchicine (2.5 mg/kg) resulted in detectable liver injury as revealed by elevations of serum transaminases. While the lowest dose of colchicine (0.1 mg/kg) did not influence bile secretion, the two higher doses caused a slight choleretic effect at 24 hr. The highest dose caused a transient inhibition of bile flow, but this effect was no longer evident at 6 hr. Biliary excretion of PG was inhibited significantly by colchicine within 6 hr after administration, an effect that was also persistent at 24 hr. Colchicine at a 1 mg/kg dose did not cause any adverse effect on hepatobiliary function. Therefore, for the interactive toxicity study with CCl4, 1 mg colchicine/kg was chosen as a moderate dose which did not cause any significant adverse effect on hepatobiliary function. Biliary excretion of PG was significantly lower in rats at 6 and 24 hr after the combination treatment with colchicine + CCl4 than in rats receiving either CCl4 or colchicine alone. In contrast, rats receiving CCl4 alone or colchicine + CCl4 showed a significant increase in cumulative bile flow at 6 hr, whereas, at 24 hr, the bile flow was increased significantly in rats receiving colchicine regardless of CCl4 treatment. The data suggest that colchicine pretreatment leads to significant inhibition of hepatobiliary excretion in CCl4 treated rats. Serum alanine transaminase and aspartate transaminase levels were elevated significantly after the colchicine + CCl4 combination, indicating hepatic injury.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of colchicine on hepatobiliary function in CCl4 treated rats. 176 17

The immunotoxicity, hepatotoxicity, and nephrotoxicity of subacute exposure to carbon tetrachloride (CCl4) were evaluated in young adult (8-9 weeks old) male Fischer 344 rats dosed by gavage with CCl4 for 10 consecutive days at 0, 5, 10, 20 or 40 mg/kg/day. Two days following the last treatment rats were evaluated for alterations in immune function by monitoring the following: body and lymphoid organ weights; mitogen and mixed leukocyte reaction lymphoproliferative responses; natural killer cell activity; and cytotoxic T lymphocyte responses. A separate group of similarly dosed rats was immunized with sheep red blood cells (SRBC) on Day 9 of dosing, and the primary antibody response was assessed 4 days later. Hepatic and renal toxicity were assessed 2 days after the last treatment by monitoring organ weights, serum indicators of hepatic and renal damage, and hepatic cytochrome P450 levels, as well as by histological evaluation. Significant increases in relative liver weights were observed in rats dosed at 40 mg/kg/day. Histologically, these livers displayed mild to moderate vacuolar degeneration and minimal to mild hepatocellular necrosis. In addition, serum levels of aspartate aminotransferase and alanine aminotransferase were elevated at this dosage, as well as at 20 mg/kg/day. There were no renal effects observed at these dosages of CCl4. In addition, no consistent alterations were observed in the immune parameters examined in these same animals nor in the rats immunized with SRBC. Furthermore, there was no difference in the antibody response to SRBC in another set of rats dosed at 40, 80 or 160 mg/kg/day CCl4. These results indicate that CCl4 is not immunotoxic in the rat at dosages that produce overt hepatotoxicity.
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PMID:Immunotoxicologic assessment of subacute exposure of rats to carbon tetrachloride with comparison to hepatotoxicity and nephrotoxicity. 183 55


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