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)

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 purpose of this study is to determine the effect of short-term social drinking on hepatitis B virus (HBV) replication as measured by serum levels of hepatitis B virus DNA (HBV-DNA). We studied five male carriers of hepatitis B e antigen who were social drinkers. Levels of HBV-DNA, blood alcohol, and aspartate aminotransferase (AST) were measured during abstinence from alcohol, before and during a test dose (29.8 g) of alcohol which followed one week of abstinence, and before and during the same test dose which followed social drinking for one week. We observed no significant changes in HBV-DNA or AST levels. These data suggest that a single one-week period of social drinking in patients with chronic HBV infection does not cause enhanced viral replication. The risks of repeated ingestion of moderate amounts of alcohol by such patients have not been established. Interpretation of our data is limited by the small number of subjects, and further studies are needed. Nevertheless, our results are consistent with published recommendations that social drinking by nonalcoholic HBV carriers should be restricted but need not be totally forbidden.
Alcohol Clin Exp Res 1987 Dec
PMID:A preliminary study of hepatitis B virus replication during short-term (7-day) social drinking. 332 8

The ability of trichloroethylene (TCE) and selected metabolites to induce single-strand breaks in hepatic DNA of male B6C3F1 mice and Sprague-Dawley rats in vivo was evaluated using an alkaline unwinding assay. Doses of TCE of 22-30 mmol/kg were required to produce strand breaks in DNA in rats, whereas a dose of 11.4 mmol/kg was sufficient to increase the rate of alkaline unwinding in mice. To assess the importance of TCE metabolism to this response, rats were subjected to pretreatments of ethanol, phenobarbital, TCE, or the appropriate vehicle for 4 days prior to challenge doses of TCE. Phenobarbital and TCE, but not ethanol pretreatments, reduced the dose of TCE required to produce significant increases in single-strand breaks. In another series of experiments, mice and rats were treated with metabolites of TCE. Trichloroacetate, dichloroacetate, and chloral hydrate induced strand breaks in hepatic DNA in a dose-dependent manner in both species. Strand breaks in DNA were observed at doses that produced no observable hepatotoxic effects as measured by serum aspartate aminotransferase and alanine aminotransferase levels. The slopes of the dose-response curves and the order of potency of these metabolites differed significantly between rats and mice, suggesting that different mechanisms of single-strand break induction may be involved in the two species. These data provide a potential explanation for the different sensitivity of mice and rats to the hepatocarcinogenic effects of TCE.
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PMID:Induction of strand breaks in DNA by trichloroethylene and metabolites in rat and mouse liver in vivo. 337 13

727 consecutive drunken drivers were studied for laboratory markers of excessive alcohol consumption. Serum gamma-glutamyltransferase and alanine aminotransferase showed no differences and aspartate aminotransferase and blood alcohol concentration only small differences between groups of first and repeating drunk driving offenders. The best laboratory test to differentiate the repeating offenders with probably more serious alcohol problems from the first offenders was in our material serum acetate, the mean serum acetate level of the repeating offenders being highly significantly (P less than 0.001) higher than that of the first offenders or nonalcoholic controls. Serum acetate also differentiated first offenders from nonalcoholic controls (P less than 0.001). Our results suggest that serum acetate could be used for the screening of problem drinking among drunken drivers.
Alcohol Alcohol 1988
PMID:Increased serum acetate as a marker of problem drinking among drunken drivers. 339 Feb 36

The EXPERT consultation system-building tool, a knowledge-based artificial intelligence program developed at Rutgers University, has been applied to the development of a laboratory consultation system facilitating sequential laboratory testing and interpretation. Depending on the results of a basic panel of laboratory tests, the system requests that specific secondary tests be performed. Input of these secondary findings can result in requests for tertiary testing, to complete the database necessary for interpretation. Interpretation of all results is based upon final inferences from the collected findings through a series of rules, a hierarchical network that yields an efficient production system not easily obtained through conventional programming. The rules included in this model are based upon initial results for total protein, calcium, glucose, total bilirubin, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase, thyroxin, hemoglobin, mean corpuscular volume, and the concentrations of four drugs. Pertinent clinical history items included are jaundice, diabetes, thyroid disease, medications, and ethanol. Implementing this system in a laboratory-based accelerated testing program involving outpatients maximized the effective use of laboratory resources, eliminated useless testing, and provided the patient with low-cost laboratory information.
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PMID:Application of the EXPERT consultation system to accelerated laboratory testing and interpretation. 352 78

We studied a consecutive series of 204 patients who were admitted to a hospital for addictive diseases during 40 months and who had a liver biopsy. Parenteral drug abusers (n = 34) were significantly younger than alcohol abusers (n = 23) or abusers of both (n = 147) and had lower levels of serum alkaline phosphatase, total bilirubin, and aspartate aminotransferase than the other two groups. Chronic active hepatitis and chronic persistent hepatitis were more frequent (p less than 0.001) in abusers of parenteral drugs alone, whereas cirrhosis was found most often (p less than 0.001) in abusers of both alcohol and parenteral drugs. Cirrhosis was present in 10 of 39 (26%) simultaneous abusers of alcohol and parenteral drugs compared with 58 of 96 (60%) alcohol-abusing former parenteral drug abusers (p less than 0.001). Methadone maintenance treatment was not associated with cirrhosis. Thus, methadone-maintained patients who abuse alcohol and develop cirrhosis should remain in methadone maintenance treatment and receive concomitant alcoholism treatment. Also, these data further support the hypothesis that abusers of both alcohol and parenteral drugs have an increased risk of developing cirrhosis.
Alcohol Clin Exp Res 1986 Oct
PMID:Chronic liver disease in abusers of alcohol and parenteral drugs: a report of 204 consecutive biopsy-proven cases. 354 73

Since ethanol consumption decreases hepatic aminotransferase activities in vivo, mechanisms of ethanol-mediated transaminase inhibition were explored in vitro using mitochondria-depleted rat liver homogenates. When homogenates were incubated at 37 degrees with 50 mM ethanol for 1 hr, alanine aminotransferase decreased by 20%, while aspartate aminotransferase was unchanged. After 2 hr, aspartate aminotransferase decreased by 20% and by 3 hr, alanine and aspartate aminotransferases were decreased by 31 and 23%, respectively. Levels of acetaldehyde generated during ethanol oxidation were 525 +/- 47 microM at 1 hr, 855 +/- 14 microM at 2 hr, and 1293 +/- 140 microM at 3 hr. Although inhibition of alcohol oxidation with methylpyrazole or cyanide markedly decreased ethanol-mediated transaminase inhibition, neither incubation with acetate nor generation of reducing equivalents by oxidation of lactate, malate, xylitol, or sorbitol altered the activity of either enzyme. However, semicarbazide, an aldehyde scavenger, prevented inhibition of both aminotransferases by ethanol. Moreover, incubation with 5 mM acetaldehyde for 1 hr inhibited alanine and aspartate aminotransferases by 36 and 26%, respectively. Cyanamide, an aldehyde dehydrogenase inhibitor, had little effect on ethanol-mediated transaminase inhibition. Thus, metabolism of ethanol by rat liver homogenates produces transaminase inhibition similar to that described in vivo and this effect requires acetaldehyde generation but not acetaldehyde oxidation. Since addition of pyridoxal 5'-phosphate to assay mixes did not reverse ethanol effects, aminotransferase inhibition does not result from displacement of vitamin B6 coenzymes.
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PMID:Evidence for the generation of transaminase inhibitor(s) during ethanol metabolism by rat liver homogenates: a potential mechanism for alcohol toxicity. 366 1

Protection against the toxic effects of chronic alcohol consumption was observed in male guinea pigs maintained on a high-ascorbic-acid diet (vitamin C-deficient chow plus 2.0 mg ascorbic acid/ml drinking water) as compared to animals on a low-ascorbic-acid diet (vitamin C-deficient chow and from 0.025 to 0.050 mg ascorbic acid/ml drinking water). Alcohol was orally administered to the guinea pigs at a dose of 2.5 g/kg for up to 14 weeks. Levels of serum aspartate aminotransferase and serum alanine aminotransferase were significantly elevated in animals on the low-ascorbic-acid diet that received alcohol, 120 and 250%, respectively. In contrast, in animals on the high-ascorbic-acid diet that received alcohol, levels of alanine aminotransferase were not significantly elevated and levels of aspartate aminotransferase were elevated 50%. In addition, some of the animals on the low-ascorbic-acid diet that received alcohol for 12 to 14 weeks developed hepatic steatosis and necrosis, whereas none of the animals on the high-ascorbic-acid diet that received alcohol for the same length of time manifested these changes.
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PMID:Ascorbic acid chronic alcohol consumption in the guinea pig. 371 80

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

The role of glucocorticoids in the increase by cold-exposure of the effect of alanine on the malate-aspartate shuttle was studied in perfused rat liver. The capacity of the shuttle was evaluated by measurement of changes in both the rate of glucose production from sorbitol and the ratio of lactate to pyruvate during ethanol oxidation (Biomed. Res. 6, Suppl., 1986). The effect of alanine on the shuttle capacity was decreased by adrenalectomy. When 1.5 mg/kg dexamethasone sulfate was administrated to adrenalectomized rats kept at 24 or 4 degrees C, once daily for 5 days, the effect of alanine on the shuttle increased its capacity to the level of sham-operated rats that had been exposed to 4 degrees C for 5 days. The effects of dexamethasone were blocked by the coadministration of tetracycline with the agent. Cold exposure and steroid replacement had little effect on the alanine-induced elevation of the levels of aspartate, glutamate, and alpha-ketoglutarate in liver cells. The increase of the effect of alanine could not be explained only by changes in the activity of NAD+ malate dehydrogenase and aspartate aminotransferase. The results suggest that cold exposure and replacement treatment with glucocorticoids modulate equally the effect of alanine on the capacity of the malate-aspartate shuttle.
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PMID:Effects of alanine on malate-aspartate shuttle in perfused livers from cold-exposed rats. 376 24


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