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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The propensity of chlordecone (CD) to potentiate hepatotoxic and lethal effects of CCl4 is well established. Mirex (M), a close structural analogue of CD, or phenobarbital (PB), powerful inducers of hepatic microsomal drug metabolizing enzymes, are much weaker potentiators of CCl4 toxicity. The purpose of this study was to test the possibility that CD potentiates the toxicity of CCl4 by increasing the metabolism of CCl4 to a greater degree than either PB or M. We compared the in vivo metabolism of CCl4 in rats pretreated with CD, M, or PB, by measuring the hepatic content of 14CCl4, the expiration of 14CCl4, expiration of 14CCl4-derived 14CO2, and lipid peroxidation. Male Sprague-Dawley rats (250-270 g) were pretreated with a single oral dose of CD (10 mg/kg), M (10 mg/kg), or corn oil vehicle (1 ml/kg). PB pretreatment consisted of an ip injection of sodium PB (80 mg/kg) in saline (0.9%) for 2 successive days. Twenty-four hours later, 14CCl4 (0.1 ml/kg; sp act: 0.04 mCi/mmol) was administered ip in corn oil and the radioactivity present in the expired air was collected for 6 hr. Excretion of the parent compound as represented by the 14C label in the toluene trap was unchanged by any of the pretreatments. Expiration of 14CO2 measured during the 6 hr after CCl4 administration was increased in animals pretreated with PB or CD. In vivo lipid peroxidation measured as diene conjugation in lipids extracted from the livers was increased to a similar extent in animals pretreated with PB and CD, whereas the serum transaminases (ALT, AST) were significantly elevated only in animals pretreated with CD.M did not affect 14CO2 production and was without a significant effect on the lipid peroxidation. The radiolabel present in the liver at 6 hr showed no difference in hepatic content of free 14CCl4 among the groups, but the covalently bound label present in the lipid fractions of the livers pretreated with PB was elevated in comparison to CD and M treatments. These data indicate that a single oral administration of CD (10 mg/kg) 24 hr prior to CCl4 administration (100 microliter/kg) enhances the oxidative metabolism of CCl4 but to a lesser extent than PB (80 mg/kg, ip, twice), which is in inverse relationship to the potentiation of the hepatotoxic and lethal effects of CCl4 associated with these pretreatments.
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PMID:In vivo metabolism of CCl4 by rats pretreated with chlordecone, mirex, or phenobarbital. 245 66

In a cross-sectional study of 181 male workers of a rotogravure printing plant, most of whom were exposed to toluene levels well above the GDR threshold limit values, 55 subjects revealed pathological liver screening values (activities of serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase; liver size). The differential diagnostic examination showed in 51 out of these 55 subjects an association with competing factors such as alcohol abuse (78%) and overweight (40%), to a slight extent disorders of fat and carbohydrate metabolism and of the gallbladder. Drug intake did not play any role. The variance and regression analyses of the biochemical data have shown that alcohol significantly and considerably increases the activities of all three enzymes tested. Bodyweight had a similar, but less pronounced, significant effect. On the other hand, in subjects with a higher alcohol intake the activities of liver enzymes in highly toluene exposed subgroups were significantly and clearly lower than among slightly toluene exposed workers.
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PMID:Epidemiological study on the hepatotoxicity of occupational toluene exposure. 289 31

Abnormal result of liver function tests (elevated levels of AST, ALT activity) and/or abnormal haematological values (low platelet counts, leucocytosis, relative lymphocytosis) were observed in 49 of 200 workers exposed to toluene and/or xylene vapours for 5-20 years. Thirty of the affected workers were treated per os with Legalon (MADAUS, FRG) t.i.d. for 30 days. The remaining 19 were left without treatment. Under the influence of Legalon the liver function tests and the platelet counts significantly improved. The leukocytosis and relative lymphocytosis showed a nonsignificant tendency of improvement.
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PMID:Protective effect of Legalon in workers exposed to organic solvents. 307 56

An unresolved controversy is whether exposure to organic solvents in the workplace causes hepatotoxicity. From a medical surveillance study of 289 printing factory employees who were exposed primarily to toluene, we identified eight workers who had persistently abnormal serum transaminase and/or alkaline phosphatase values. The eight men were generally healthy and gave no history of taking medications or of drinking ethanol to excess. None was obese or diabetic. Six patients had hepatomegaly based on physical examination. All eight had mild elevations (less than 2 to 3 times the upper value of normal) of serum transaminases [alanine (ALT) and aspartate aminotransferase (AST)]. However, there was a marked increase in the ratio of ALT/AST (mean = 1.61). In each case, liver biopsy revealed mild, pericentral fatty change. Our results, consistent with those previously published by some others, suggest that pericentral fatty liver with mild "reactive hepatitis" is the most likely diagnosis in workers exposed to solvents for whom common causes of mild liver test abnormalities have been excluded. An increased ALT/AST ratio may represent a convenient, previously unrecognized indicator of this condition.
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PMID:Liver structure and function in print workers exposed to toluene. 261 34

The hepatotoxic properties of concurrent chronic oral ethanol ingestion and acute toluene inhalation were evaluated. Male rats were maintained on ethanol-containing or control liquid diets for 29 days. Animals of each group were subjected to five 20-min exposures to 10 000 ppm toluene with 30 min of room air inhalation between exposures on days 22, 24, 26, and 28 of liquid diet feeding. Some of the ethanol-fed animals were withdrawn from ethanol 14 h before exposure. Ethanol-withdrawn animals displayed an increased sensitivity to the narcotic action of toluene. Animals were sacrificed and assays performed on day 29. Stress markers (plasma corticosterone, free fatty acid, and glucose) were not affected by treatments. A modest elevation in plasma aspartate aminotransferase occurred in non-withdrawn animals receiving both ethanol and toluene. Ethanol-toluene exposure increased both relative liver weight and liver triglycerides. Toluene antagonized the hypertriglyceridemia associated with chronic ethanol ingestion. This study indicates that combined ethanol and toluene exposure has minor potential to induce acute liver injury, but results in altered deposition of hepatic triglycerides.
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PMID:The hepatotoxic potential of combined toluene-chronic ethanol exposure. 374 Nov 43

Studies were made with male Wistar rats on the effects of 50% food restriction on the metabolism of eight organic solvents (chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethylene, trichloroethylene, benzene, toluene and styrene) and on the hepatotoxicity induced by carbon tetrachloride inhalation at 400 ppm for 4 h. The activities of liver drug-metabolizing enzymes for these solvents were enhanced almost equally without exception by one-day food restriction, although the restriction produced no significant increase in the microsomal protein and cytochrome P-450 contents. Carbon tetrachloride hepatotoxicity was enhanced by the food restriction, as evidenced by a marked increase of serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) activities in the food-restricted rats. Histological findings of the liver also supported this finding. Thus, food restriction enhances metabolism of organic solvents in the liver, and can modify toxicity of some chemicals such as carbon tetrachloride, which need metabolic activation to become cytotoxic.
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PMID:[Effects of one-day food restriction on the metabolism and toxicity of organic solvents in rats]. 376 20

The serum activities of liver enzymes of car painters (N = 102) exposed to a mixture of solvents [toluene, xylene, and other constituents; about half the threshold limit value recommended by the American Conference of Governmental Industrial Hygienists (ACGIH) in 1981] were compared with those of age-matched referents (N = 102). The activities of aspartate aminotransferase, alanine aminotransferase, ornithine carbamoyl transferase, and gamma glutamyl transferase did not differ between the exposed and the nonexposed groups. Simultaneous neurophysiological and ophthalmological examinations of the same car painters had distinguished subgroups of "solvent-affected" and "non-affected" car painters. The enzyme activities were not higher in the "affected" subgroups than in the "nonaffected" ones. The results suggest that car painters' exposure to organic solvents (at the overall level of half the threshold limit value of the ACGIH) does not increase liver enzyme activities in routine tests.
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PMID:Car painters' exposure to a mixture of organic solvents. Serum activities of liver enzymes. 612 9

Serum enzymes (aspartate transaminase, alanine transaminase, alkaline phosphatase (ALP), gamma-glutamyltransferase, and creatine kinase (CK] were measured in 296 young persons who admitted to recent inhalation of solvents, usually toluene based glues. In general, results fell within expected adult reference ranges except for ALP and CK. About 60% of subjects had CK activities above the upper reference limit and these activities were investigated in terms of their isoenzyme composition. CK B subunit activity was measured in 90 subjects with raised total CK activities. In five instances the CK B subunit activity was judged abnormal and in two subjects the presence of CK BB was confirmed. These two subjects were thought to have a circulating macro CK, type 1. It is concluded that the increased total CK activity found in this group of solvent abusers was due to physical activity, but a contribution from specific muscle toxicity by solvents cannot be excluded.
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PMID:Observed activities of serum creatine kinase: total and B subunit activity and other enzymes in young persons abusing solvents. 614 4

The Authors have studied AST and ALT enzymatic activities in the workers of two firms, the former of which (tannery) with a high and the latter (boot and shoe factory) with a low level of hepatic-toxic risk. The influence of various trouble factors such as age, sex and seniority was eliminated through appropriate statistical techniques. A significant difference was evidenced between AST and ALT levels in two firms, chiefly attributable to the quantity and quality of the substances utilized in the two technological cycles: trichloroethylene, chromium, sulphuric acid, mineral oils, ammonia, N-hexane, pentanes acetone, ciclo hexane, methanol, ethyl acetate, isopropyl acetate, toluene, methylene chloride.
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PMID:[Levels of aspartate aminotransferase and alanine aminotransferase in two factories with various hepato-toxic risks]. 734 21


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