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:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hepatonecrogenic properties of chloroform (CHCl3) can be modified by the administration of various chemicals. The ability of methyl isobutyl ketone (MIBK) and its two major metabolites, 4-methyl-2-pentanol (4MPOL) and 4-hydroxymethyl isobutyl ketone (4-OHMIBK) to potentiate the liver injury induced by CHCl3 was assessed in rats. The parent compound and both metabolites significantly increased the liver damage induced by CHCl3, as demonstrated by the elevation of the plasma activity of two transferases alanine aminotransferase and ornithine carbamoyl transferase and by the severity of the morphological changes. Moreover, the minimally effective dosage needed to potentiate CHCl3-induced hepatotoxicity was approximately 5 mmol/kg for the three compounds. We also studied the inducing properties of MIBK (cytochrome P-450 liver content and the activity of aniline hydroxylase, 7-ethoxycoumarin O-deethylase, and aminopyrine N-demethylase). Cytochrome P-450 content and the oxidation of aniline and 7-ethoxycoumarin were significantly increased with either a single (7.5 mmol/kg or greater) or a multiple (5.0 and 7.5 mmol.kg-1.day-1 for 5 days) administration of MIBK. An increase in the activity of the aminopyrine demethylase was also elicited by the repetitive administration of MIBK. With gel electrophoresis, we found that MIBK significantly increased the 52.1- and 54.1-kDa proteins, corresponding most probably to P-450 isozymes.
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PMID:Potentiation of chloroform-induced hepatotoxicity by methyl isobutyl ketone and two metabolites. 239 Jul 35

Exposure to chlordecone (CD, Kepone) is known to increase the hepatotoxicity of chloroform (CHCl3) in rats. A time-course analysis was conducted relating several indices of biotransformation capacity with the ability of CD to potentiate CHCl3-induced hepatotoxicity. Male Sprague-Dawley rats were given a single administration of corn oil alone or CD (50 mg/kg, po) dissolved in corn oil. At 2, 4, 8, 16, 20, 24, or 32 days posttreatment, groups of rats were killed and their livers were analyzed for (i) cytochrome P-450, NADPH-dependent cytochrome c reductase, cytochrome b5 and glutathione content or (ii) in vitro irreversible binding of 14CHCl3-derived radiolabel to microsomal protein. Similarly treated rats were challenged (2-32 days posttreatment) with CHCl3 (0.5 mL/kg po); 24 h later, liver damage was assessed by plasma alanine aminotransferase (ALT), plasma ornithine carbamyl transferase (OCT), plasma bilirubin, and hepatic glucose-6-phosphatase. CD potentiation was maximal 2 days posttreatment; and enhanced susceptibility to CHCl3 persisted up to 20-24 days post-CD treatment. In a parallel study animals treated with chlordecone were killed 8, 16, 20, 24, or 32 days later. Blood, kidney, liver, and adipose tissue samples were taken and analyzed for chlordecone content. The results suggest that a general temporal correlation exists between biotransformation rate (microsomal 14C binding), chlordecone content, and the severity of liver injury; the other parameters monitored do not appear to relate directly to the potentiation.
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PMID:Temporal relationships between biotransformation, detoxication, and chlordecone potentiation of chloroform-induced hepatotoxicity. 242 14

Elevated levels of serum enzymes are frequently associated not only with alcohol-related organ damage but also with excessive alcohol consumption and alcoholism without significant tissue injury. However, both in the early detection of alcoholism as well as also in the diagnosis of alcohol-related diseases the sensitivities and specificities of these enzyme markers vary considerably. They may be influenced by nonalcohol-related diseases, enzyme-inducing drugs, nutritional factors, metabolic disorders, age, smoking, etc. Consequently, we have neither a single laboratory test--enzyme marker--nor a test combination that is reliable enough for the exact diagnosis between alcohol- and nonalcohol-related organ damage. In most cases it is possible to determine the tissue from which the elevated enzyme is derived, but only occasionally enzyme changes reflect the quantity of the tissue injury. Gamma-glutamyltransferase (GGT) is the most widely used laboratory marker of alcoholism and heavy drinking, detecting 34-85% of problem drinkers and alcoholics. However, the unspecificity of increased serum GGT limits its use for general screening purposes. Its value in the follow-up of various treatment programs, however, is well established. An elevated level of serum aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) in an alcoholic or a heavy consumer indicates alcohol-induced organ damage. The use of test combinations significantly improves the information received with single serum enzyme determinations. An ASAT/ALAT ratio greater than 1.5 can be considered as highly suggestive for the alcoholic etiology of the liver injury. Still better discrimination between alcoholic and nonalcoholic origin of the liver disease may be achieved by the determination of the ratio of GGT to alkaline phosphatase. If this ratio exceeds 1.4 the specificity of the finding in favor for alcoholic liver injury is 78%. The determination of the mitochondrial isoenzyme of ASAT also improves the diagnostic value of ASAT determination. The ratio of mitochondrial isoenzyme to total over 4 is highly suggestive for alcohol-related liver injury. In general, however, the determination of serum activities of other enzymes such as ornithine carbamyl transferase, lactate dehydrogenase, isocitrate dehydrogenase, sorbitol dehydrogenase, alcohol dehydrogenase, guanase, aldolase, alkaline phosphatase or glutathione S-transferase do not significantly improve the diagnostic information obtained with more conventional laboratory markers of liver injury.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Use of enzymes for the diagnosis of alcohol-related organ damage. 243 6

The purpose of this study was to investigate whether the tissue distribution of chlordecone (CD) and mirex (M) might explain the difference in the potentiation of CHCl3 liver injury. Male Sprague-Dawley rats received either a single oral dose of CD or M (1, 2.5, 5, 10, 25, or 50 mg/kg) or three single daily doses of CD or M (0.5, 2, or 10 mg/kg). Eighteen hours following the last treatment, the animals were divided into two groups. The first group was killed and residues of CD or M in plasma, kidney, liver, and adipose tissue were measured by gas-liquid chromatography. The other group received CHCl3 (0.5 ml/kg, po) and was killed 24 hr later. Biochemical and histological indices of liver injury were evaluated. CD administered either singly or repetitively is more effective than M in potentiating the CHCl3-induced liver injury. This was exhibited by a higher increase in the plasma activities of the enzymes alanine aminotransferase and ornithine carbamoyl transferase and a greater alteration of the morphological pattern. There was a very good correlation between biochemical and histological indices. However, the severity of the liver injury did not parallel tissue concentrations. With M, a relatively poor potentiation of the liver damage was observed although adequate hepatic concentrations were present.
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PMID:Chloroform interaction with chlordecone and mirex: correlation between biochemical and histological indices of toxicity and quantitative tissue levels. 244 11

Serological tests may be of value in differentiating acute and chronic bile duct obstruction because the rate of alteration of hepatic cellular integrity and function will affect the rate of cellular product release. In a canine model the common bile duct was obstructed either suddenly (N = 7) or gradually (N = 5). A control group (N = 5) had the common bile duct dissected free from the surrounding tissues. Blood was taken before and 1, 2, 4, 7, 11, 14, 17, 21, and 28 days after initiating obstruction. Serum alkaline phosphatase, bilirubin, aspartate aminotransferase, alanine aminotransferase, ornithine carbamyl transferase, and gamma-glutamyl transferase levels were significantly greater with sudden compared to gradual occlusion, and the values were larger than those in the control. The range of values of alkaline phosphatase, bilirubin, and aspartate aminotransferase did not overlap in the acute and chronic groups at specific times. Serum albumin and total protein were normal in all groups. The magnitude of alkaline phosphatase, aspartate aminotransferase, and bilirubin elevation may help in the differentiation of acute and chronic biliary obstruction.
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PMID:Diagnostic value of liver function tests in bile duct obstruction. 256 54

This investigation was undertaken to assess the potential of ingested 1,2-dibromo-3-chloropropane (DBCP) to cause testicular and hepatorenal injury, in light of the paucity of data applicable to risk assessment of DBCP in drinking water. Adult male Sprague-Dawley rats were supplied ad libitum with water containing 0, 5, 50, 100, and 200 ppm DBCP for 64 days. A dose-related decrease in water consumption occurred during the study. The 200-ppm animals drank less than half as much water as controls, consumed less food, and subsequently exhibited significantly lower body weight gain. DBCP ingestion thus was not directly proportional to the level of chemical in the water, although daily and cumulative intake of DCP were concentration dependent. Average daily intake of DBCP for the 64-day exposure period was as follows: 5 ppm = 0.4 mg/kg/day; 50 ppm = 3.3 mg/kg/day; 100 ppm = 5.4 mg/kg/day; 200 ppm = 9.7 mg/kg/day. Blood samples were taken after 2, 4, and 6 weeks of exposure and at the terminal sacrifice and assayed for serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, sorbitol dehydrogenase, and ornithine-carbamyl transferase activities and BUN levels. No evidence of liver damage at any exposure level was indicated by either the clinical chemistry indices or histopathology. Histologic examination revealed an apparent increase in the number of nuclei per renal proximal tubule cross-section in the 200-ppm group, possibly indicative of an increased turnover of proximal tubular cells. A slight, but statistically significant, decrease in absolute testicular weight was manifest in the 200-ppm animals, although the decrease was not significant when testicular weight was calculated as g/100 g body wt. Epididymal sperm counts and serum luteinizing hormone, follicle stimulating hormone, and intratesticular testosterone levels were not altered by any dose of DBCP. A qualitative histopathological examination of the testicular seminiferous epithelium failed to reveal any abnormalities in the spermatogenic process.
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PMID:Assessment in rats of the gonadotoxic and hepatorenal toxic potential of dibromochloropropane (DBCP) in drinking water. 262 Jul 97

The serum activities of the liver enzymes alanine aminotransferase, aspartate aminotransferase, ornithine carbamyl transferase, and gamma-glutamyl transferase were examined in 47 paint industry workers and unexposed age matched referents. The workers were exposed to a mixture of industrial solvents, of which xylene was the main component in most cases. The median total exposure was about 50% of Swedish 1981 threshold limit values according to measurements of individual solvent exposure performed at the same time. No differences in enzyme activities were shown either when the whole exposed and referent groups were compared or when the five workers with outstanding solvent exposures of five times the TLV or more were compared with their referents. It is concluded that in most workers the liver seems to remain largely undamaged from inhalation exposure to a commonly used mixture of non-chlorinated solvents. In many workers this seems to hold true even for high exposures for limited periods.
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PMID:Normal serum activities of liver enzymes in Swedish paint industry workers with heavy exposure to organic solvents. 286 77

A survey of aminotransferase activities present in a cell-free extract of the anaerobic protozoan, Trichomonas vaginalis was performed. 2-Oxoglutarate, oxaloacetate or phenylpyruvate acted as effective amino acceptors with tyrosine, phenylalanine, tryptophan, leucine, valine, isoleucine, aspartate, alanine, ornithine or lysine. Arginine, serine, glutamine, glycine, beta-alanine and gamma-aminobutyrate were not active as amino donors. With pyruvate as acceptor, significant, yet low, activity was seen only with glutamate, lysine or phenylalanine. Partial purification of enzymes catalysing transamination of leucine, valine, isoleucine, alanine, ornithine and lysine were carried out. A single enzyme catalysed the transamination of ornithine and lysine. The substrate specificity of this enzyme is novel. A separate enzyme catalysed the transamination of all three branched chain amino acids. A third enzyme catalysed the alanine aminotransferase reaction. A fourth enzyme catalysing the transamination both of aromatic amino acids and aspartate has previously been purified [Lowe, P.N. and Rowe, A.F. (1985) Biochem. J. 232, 689-695].
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PMID:Aminotransferase activities in Trichomonas vaginalis. 309 39

This study demonstrates that the exposure of phenobarbitone-treated rats to halothane at an oxygen concentration of either 10% or 14% results in marked decreases in cytochrome P-450 content and aminopyrine demethylase activity in animals sacrificed from 1 to 48 hr post-exposure. The alterations observed in the hepatic mixed function oxidase system were accompanied by increases in serum alanine aminotransferase (ALT), ornithine carbamyl transferase (OCT) and changes in liver pathology. However, the minor changes in cytochrome P-450 content and aminopyrine demethylase activity observed following exposure of enzyme-induced rats to halothane under normoxic conditions (i.e. 21% oxygen) were not of a sufficient magnitude to lead to hepatic cell necrosis. Halothane administration in the absence of phenobarbitone pretreatment (i.e. 21% oxygen) or during hypoxia alone (i.e. either 10% or 14% oxygen) did not result in any systematic changes in the parameters assayed. The results suggest that cytochrome P-450 may catalyse its own inactivation by virtue of greater free radical production under conditions which favour the non-oxygen dependent metabolism of halothane. The impairment in microsomal function as evidenced by decreases in cytochrome P-450 and aminopyrine demethylase activity are considered to occur as a primary consequence of the reductive metabolism of halothane. Data are presented which support the concept of the initiation of hepatic damage occurring during the period of anaesthesia with halothane.
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PMID:Changes in rat hepatic microsomal mixed function oxidase activity following exposure to halothane under various oxygen concentrations. 310 40

Male F344 rats were exposed by gavage to samples of complex mixtures and evaluated 24 hr later. Seven of the 10 samples caused death at doses ranging from 1 to 5 ml/kg body wt. Eight of the 10 samples were hepatotoxic based on histopathologic evaluation; 6 were centrilobular and 2 were periportal hepatotoxicants. The waste samples exerted toxicity through different mechanisms, as indicated by differences in the severity and lobular location of the tissue damage. Nine of the 10 samples caused an increase in the ratio of liver weight to body weight (relative liver weight). With histopathological evaluation as the criterion, relative liver weight was the single best indicator of hepatotoxicity. Exposure to several of the waste samples increased serum total bilirubin and serum enzyme activities of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, and ornithine carbamyl transferase. As a battery, but not individually, the serum indicators separated the 8 hepatotoxic samples from the 2 nonhepatotoxic samples. In general, the hepatotoxicity of the waste samples did not appear to be readily predicted from (partial) chemical characterization data. An approach that includes both chemical characterization and biological testing should provide valuable information regarding the hazardous nature of complex wastes.
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PMID:Lethality and hepatotoxicity of complex waste mixtures. 337 Dec 93


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