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)

Methanol, ethanol and isopropanol were tested for the ability to change effects of chlorinated hydrocarbons on the alanine aminotransferase (ALAT = GPT; EC 2.6.1.2.) activity in serum of rats. The alcohols were given once orally or repeatedly together with drinking water. After additional i.p. administration of chloroform we found a significant increase of ALAT activities in the order: isopropanol greater than or equal to methanol greater than ethanol, both after single and repeated application of the alcohols. Together with trichloroethene and 1.1.2.2-tetrachloroethane no such elevations were found. The results suggest that different mechanisms of action could be underlying.
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PMID:Influence of alcohol pretreatment on effects of chloroform in rats. 317 85

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

About 90 per cent of morbidly obese patients show histological abnormalities of the liver. One third of patients have fatty change involving more than 50 per cent of hepatocytes. Fatty liver disease can be divided into four histological groups: Fatty liver, fatty hepatitis, fatty liver with portal fibrosis, and cirrhosis. Most patients show only fatty change. Alcohol, drugs, diabetes, poor nutrition, and weight-reducing surgery contribute to progressive liver damage, but morbid obesity alone may lead to severe disease showing all the features of alcoholic hepatitis and may end in cirrhosis and liver failure. The accumulation of fat alone is unlikely to be the stimulus to inflammation and fibrosis. Only one fifth of patients have complaints that arise from the liver. The development of severe fatty liver disease may also be asymptomatic and rarely shows the florid picture associated with alcoholic hepatitis. There is poor correlation of liver function test results with morphology in obesity. ALT levels exceeding twice the normal limit have some predictive value for histological grades of severity, but they are present in few patients. Pericentral and pericellular fibrosis in prebypass liver biopsies may be an important prognostic lesion for the development of fatty hepatitis and cirrhosis. In contrast with the frequent progression to massive fatty change, inflammation and fibrosis after bypass surgery, weight loss by low-calorie dieting, or starvation is accompanied by improvement in fatty change and return of liver function tests to normal.
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PMID:Fatty liver disease in morbid obesity. 331 4

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

Male Wistar rats pretreated with ethanol (2.0 g in 80 ml liquid diet/day for 3 weeks) or phenobarbital (PB, 80 mg/kg/day ip for 4 days) were exposed by inhalation to 500, 1000, 2000, 4000, or 8000 ppm trichloroethylene (TRI) for 2 or 8 hr, and the blood concentration of TRI and the urinary concentration of TRI metabolites (trichloroethanol (TCE) and trichloroacetic acid (TCA] were determined at various times. Plasma glutamic-pyruvic transaminase (GPT) activity was measured 22 hr after the end of exposure as an indicator of hepatic damage. Both ethanol and PB enhanced TRI metabolism as evidenced by accelerated disappearance of TRI from the blood and increased excretion of total trichloro compounds (TCE + TCA) in the urine. However, the effects of ethanol and PB were different from each other: ethanol markedly enhanced the metabolism particularly at TRI concentration of 2000 ppm or lower, whereas PB enhanced it only at 4000 ppm or higher. This difference was also reflected in the effect of TRI on liver: ethanol potentiated TRI hepatotoxicity more markedly than did PB when TRI concentration remained 2000 ppm or lower, whereas PB potentiated the toxicity more markedly than ethanol when the concentration was 4000 ppm or higher. It is noteworthy that ethanol potentiated TRI hepatotoxicity at a TRI concentration as low as 500 ppm. The severity of hepatic damage expressed by plasma GPT activity essentially paralleled the urinary excretion rate of total trichloro compounds during and 4 hr after exposure (r = 0.87 to 0.93). Compared between the contribution of concentration and duration of exposure to the toxicity, a higher concentration of TRI tended to cause more severe liver damage to PB-treated rats than did a prolonged period of exposure, whereas the toxicity in ethanol-treated rats was generally more marked in rats exposed to TRI for a longer period than in rats exposed to a higher concentration.
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PMID:Ethanol-induced enhancement of trichloroethylene metabolism and hepatotoxicity: difference from the effect of phenobarbital. 338 20

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

(1) The acute effects of ethanol on protein synthesis by liver and skeletal muscle were investigated in young (95-100 g) rats. Rats were injected intraperitoneally with ethanol, 75 mmol/kg body wt; controls were injected with isovolumetric 0.15 M NaCl. After 140 min rates of protein synthesis were measured by injection of a large dose of L[4(3)H]phenylalanine and at 150 min rats were killed. (2) Fractional rates of protein synthesis in control animals were approximately four to five times greater in liver than muscle. Absolute rates were, however, comparable in liver and skeletal muscle. Ethanol reduced the fractional rate of liver protein synthesis by 5-20%; the response for muscle was relatively greater (25-30%). The decrease in the amount of protein synthesized by muscle was also greater than that by liver. (3) After 150 min, plasma gamma-glutamyl transferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase and creatine kinase activities were all decreased by 25-60%. Aspartate aminotransferase activity was increased by 42%, though this was not statistically significant. (4) Increased plasma glucose and triglycerides in ethanol-dosed rats indicated that limitations in substrate supply were not mediating factors in reducing protein synthesis. Ethanol was also able to exert its effects in the presence of elevated insulin levels. A direct effect of ethanol, or its metabolites, on protein synthesis, is therefore implied.
Alcohol Alcohol 1988
PMID:Comparison of the acute effects of ethanol on liver and skeletal muscle protein synthesis in the rat. 339 Feb 39

Since red cells transport and metabolize acetaldehyde in vivo, the effects of acetaldehyde on human red cell enzyme activities were studied. Incubation of intact red cells or undiluted red cell lysates at 37 degrees C for 4 h with 1-10 mmol/l acetaldehyde decreased only GOT, GPT and aldolase activities among the 26 enzymes tested. No inhibition occurred at 4 degrees C or when acetaldehyde was incubated with dilute hemolysates. Incubation of lysates with other reducing substrates or with acetate inhibited aldolase but not GOT or GPT. Preincubation of lysates with cyanate or fluoride markedly decreased acetaldehyde-mediated transaminase inhibition but not aldolase inhibition. Addition of pyridoxal phosphate, the vitamin B6 transaminase coenzyme, to GOT and GPT assay mixes did not reverse acetaldehyde-mediated transaminase inhibition. These findings suggest that acetaldehyde-mediated aldolase inhibition results from oxidation of acetaldehyde while transaminase inhibition results from nonoxidative acetaldehyde metabolism. When 100-200 mumol/l acetaldehyde is added to lysates at 2-h intervals and when lysates are incubated with ethanol, alcohol dehydrogenase and an NAD-regenerating system, enzyme inhibition occurs at acetaldehyde levels approaching those seen in vivo. Thus, the role of acetaldehyde-mediated enzyme inhibition in the toxicity of alcohol abuse warrants further study.
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PMID:Effects of acetaldehyde on human red cell metabolism: evidence for the formation of enzyme inhibitors. 341 86

A study was made on the possibility of synergistic effects of ethyl alcohol and lead on porphyrin metabolism in rabbits. Experimental rabbits were divided into 4 groups. Group A was the control group not given any treatment, and the other 3 groups (Groups B, C and D) were treated with ethyl alcohol, lead, and ethyl alcohol and lead respectively, for 2 months. Ethyl alcohol solution (5%) was administered to rabbits in Groups B and D as drinking water on every weekday. The average dose of alcohol was 6 ml/kg/day (18 ml/cap/day). Lead was injected intravenously to rabbits in Groups C and D at a dose of 0.5 mg Pb/kg on alternate days (3 times per week). Furthermore, a large dose of Pb was administered to other rabbits (Group C'). In rabbits treated with alcohol alone (Group B), no effect was observed in the biochemical indicators related to porphyrin metabolism. In the groups treated with lead (Groups C and C') and with lead and alcohol combined (Group D), some biochemical changes in porphyrin metabolism developed with increase of Pb-B, i.e. increase of ALA-S activity and total porphyrin content in the bone marrow, elevation of FEP level, increase of ALA-U and CP-U, and decrease of ALA-D activity in erythrocytes. Comparison of Groups C and D showed that CP-U and ALA-U increased significantly in Group D, but no significant difference was observed between both groups in FEP and in ALA-S activity in the bone marrow and liver. The other laboratory measurements, such as total porphyrin contents in the liver and plasma, and GOT or GPT level in serum, showed no significant change in all the groups. In the present study, the biochemical changes suggesting synergism of lead and ethyl alcohol were observed slightly in ALA-U and CP-U but not in ALA-S and FEP. These results suggest that these changes are essentially due to lead rather than mutual enhancement of the direct effects of these two toxins on porphyrin metabolism. However, it still remains to be determined whether or not ethyl alcohol affects the liver and kidney functions which may be related to ALA and CP excretion.
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PMID:[Effects of ethyl alcohol ingestion on the disturbance of porphyrin metabolism by lead]. 341 59

Hepatocytes from 12-day-old rats, pre and postnatally exposed to alcohol and pair-fed controls, were isolated and subfractionated in six cell subpopulations on Percoll density gradients. These cells were characterized using biochemical, stereological and cytofluorometric methods. Our results show that the low density cells (F2) are mainly perivenous cells, whereas the heavier cells (F6) were primarily periportal cells. These results were confirmed by alanine aminotransferase (ALAT), and glutamate dehydrogenase (GDH) activity levels and by stereological parameters. Alcohol seems to especially affect perivenous hepatocytes, with the damaged hepatocytes appearing in the perivenous and midzonal hepatocyte populations.
Alcohol Alcohol Suppl 1987
PMID:Effect of pre- and postnatal exposure to alcohol on perivenous and periportal neonatal rat hepatocytes. 342 91


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