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)

The inclusion of rats aboard Spacelab 3 (SL-3) allowed analyses of liver lipids, glycogen, hepatic enzymes of cholesterol, glycerolipid and sphingolipid biosynthesis, and other enzyme activities. Glycogen content was markedly elevated in livers from the flight animals compared with controls. Cholesterol was 24% (P less than 0.04) lower in livers from the experimental groups, whereas blood cholesterol was 19% higher (P less than 0.05). The activity of 3-hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzyme of steroid biosynthesis, was 80% lower (P less than 0.01). Total phospholipids and sphingolipid levels did not differ significantly. The specific activity of fatty acyl-CoA synthetase, which is responsible for activation of fatty acids, was 37% (P less than 0.05) higher in microsomes from the rats on SL-3; however, since these animals had 25% less microsomal protein (P less than 0.02), there was no difference per gram of liver. The initial enzymes of sphingolipid and glycerolipid biosynthesis were assayed; serine palmitoyltransferase was 40% lower (P less than 0.01), and glycerol 3-phosphate acyltransferase did not differ. Hepatic cytochrome P-450 content decreased by 50% after spaceflight. Enzymes that did not differ significantly between the two groups include cytochrome b5, glutathione S-transferase, tyrosine aminotransferase, aspartate aminotransferase, and cystathionase. These findings suggest that spaceflight alters hepatic metabolism of several classes of compounds.
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PMID:Hepatic function in rats after spaceflight: effects on lipids, glycogen, and enzymes. 381 60

Two new methods are developed for synthesis of conjugated antigens of o-aminoazotoluene-bovine serum albumin (o-AAT--BSA): (1) from the microsomal fraction of the guinea pig liver which contains the cytochrome-P-450-dependent monooxygenase enzymic system and (2) from the m-chloroperbenzoic acid. A possible mechanism of the covalent binding of o-AAT with albumin under the effect of monooxigenases and of their chemical model is considered. Differences of antigenic determinants in conjugated antigens of o-AAT--BSA synthetized by the chemical and enzymic methods are detected.
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PMID:[Antibody formation to o-aminoazotoluene via the administration of conjugated antigens synthesized by enzymatic and chemical methods]. 391 Apr 3

Weanling, male Sprague-Dawley rats given 10% ethanol in the drinking water and food ad lib. for up to 8 weeks consumed 17% of their calories as ethanol. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), and liver histology by light microscopy were unaffected by this treatment. Similarly, hepatic microsomal NADPH-cytochrome c reductase, ethylmorphine N-demethylase and benzphetamine N-demethylase activities were also not affected by ethanol consumption. On the other hand, cytochrome P-450 content, aniline hydroxylase activity and acetaminophen metabolism as measured by both the cysteine conjugate and the [3H]acetaminophen covalently-bound to microsomal protein were increased significantly by ethanol consumption. The maximal effect was seen by 6 weeks. The 2- to 3-fold increase in aniline and acetaminophen metabolism, the absence of liver damage, and the similarity in weight gains and caloric intakes for controls and treated animals suggest that the rat on 10% ethanol in the drinking water is a reasonable model for studies of the effect of moderate alcohol consumption on specific biochemical pathways.
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PMID:Studies on the effect of chronic consumption of moderate amounts of ethanol on male rat hepatic microsomal drug-metabolizing activity. 393 44

Rats were injected sc with 0.5 mg Cd/kg, 6 days/week, for up to 26 weeks. Hepatic and renal function and tissue Cd and metallothionein (MT) content were determined in tissues and plasma at various times after Cd injection. Cd in liver and kidney increased linearly for the first 10 weeks of treatment, but thereafter hepatic concentrations of Cd decreased by 33% whereas the content of Cd in kidney remained constant. MT in liver and kidney increased linearly during the first 12 weeks of Cd treatment to 4400 and 2300 micrograms MT/g, respectively, but rose only slightly thereafter. Circulating concentrations of MT progressively increased beginning 2 weeks after Cd treatment and were approximately 10 times control values in rats dosed with Cd for 12 or more weeks. Plasma activities of alanine and aspartate aminotransferase exhibited a time course similar to that observed with MT, and were elevated as early as the sixth week of Cd exposure. Sharp increases in activities of these enzymes also occurred after 10 to 12 weeks of dosing. Hepatic microsomal metabolism of benzo[a]pyrene and ethylmorphine was severely attenuated beginning 4 weeks after Cd. Renal injury occurred after hepatic damage, as evidenced by decreased in vitro p-aminohippuric acid uptake beginning 8 weeks after exposure. Urine outflow increased threefold 11 weeks after Cd exposure began, while urinary protein and Cd excretion increased beginning at Week 9. These data indicate the liver is a major target organ of chronic Cd poisoning, and suggest that Cd-induced hepatic injury, via release of Cd-MT, may play an important role in the nephrotoxicity observed in response to long-term exposure to Cd.
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PMID:Cadmium-induced hepatic and renal injury in chronically exposed rats: likely role of hepatic cadmium-metallothionein in nephrotoxicity. 397 9

Experiments were conducted to examine the role of zinc in the prevention of bromobenzene hepatoxicity in male rats. Bromobenzene (BB) (7.5 mmol/kg, ip) produced a marked hepatotoxicity as evidenced by increases in plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and a marked depression in hepatic glutathione (GSH) content 24 hr after administration. The administration of zinc (92 mumol Zn/kg, ip, at 48 and 24 hr prior to the bromobenzene) ameliorated the bromobenzene elevations in plasma AST (25%) and plasma ALT (50%) but did not alter the decreases in hepatic GSH. Following administration of [14C]BB, the radioactive label was distributed primarily in the cytosolic and lipid fractions derived from liver homogenates. Furthermore, the subcellular distribution of [14C]BB was not altered by zinc pretreatment. The extent of covalent binding of [14C]BB metabolites to hepatic tissue was significantly depressed in zinc-treated rats. Zinc induced the hepatic levels of metallothionein but [14C]BB did not bind to this sulfhydryl rich protein. Further experiments showed that zinc treatment depressed cytochrome P-450 content, the activity of NADPH cytochrome c reductase, and the metabolism of aniline, but not that of ethylmorphine. These studies suggest that the hepatoprotective effect of zinc against bromobenzene toxicity does not involve altered binding of the reactive toxic metabolite to glutathione or metallothionein, but it may be mediated by the inhibitory effect of zinc on the microsomal cytochrome P-450-dependent drug metabolizing system.
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PMID:Amelioration of bromobenzene hepatotoxicity in the male rat by zinc. 398

When male Sprague-Dawley rats were treated with sodium selenite (1 mg/kg, sc) 24 hr prior to or simultaneously with bromobenzene (2.5 mmol/kg, ip) and sacrificed 48 hr after the bromobenzene dose, increased levels of the activities of serum transaminases (serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) induced in the bromobenzene-treated rats were significantly reduced in the presence of selenium. However, no such reduction in the transaminases activities were observed when rats were either pretreated with selenite for 48 hr or pretreated with 0.1, 0.2, or 0.5 mg/kg of selenite. Although selenium alone had no effect on the hepatic microsomal drug metabolism, simultaneous treatment of selenite (1 mg/kg) with bromobenzene resulted only an increase in the activity of aniline hydroxylase after 48 hr as compared to that in the bromobenzene-treated group. When rats were given 2.5, 10, and 20 ppm of selenite in drinking water daily for 4 weeks prior to an ip injection of 2.5 mmol/kg of bromobenzene and were sacrificed 48 hr after bromobenzene administration, a reduction in the SGOT activities in all the pretreated groups and a reduction of SGPT activity in 20 ppm selenite-treated group were observed when compared with those in the bromobenzene-treated groups. A dose-dependent increase in hepatic GSH concentrations were observed due to such chronic selenium treatment. Treatment with selenite (1 mg/kg) 24 hr prior to bromobenzene injection (2.5 mmol/kg) increased initially both o and p-bromophenols in the rat urine at 0-7.5 hr without affecting urinary thioethers. On the contrary, the ratio of thioethers to p-bromophenol was significantly higher in both 2.5 and 10 ppm selenite-pretreated (4 weeks) rats as well as a significant increase in the ratio of thioethers to total phenolic metabolites in 10 ppm and an increase close to significant in 2.5 ppm selenite-treated rats were observed initially at 0-7.5 hr urine samples. These results indicate that acute selenium pretreatment under certain conditions, favors increased hydroxylation of the intermediate bromobenzene epoxides, whereas higher detoxification of the epoxides involving hepatic glutathione (GSH)/GSH transferases pathway is more favored due to increased biosynthesis of GSH in certain chronic selenium treated rats.
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PMID:Influence of selenium on the metabolism of bromobenzene and a possible relationship to its hepatotoxicity. 401 88

Seven patients with severe rosacea were treated with 1 mg/kg per day isotretinoin for 12 wk. There were significant increases in serum triglyceride (p less than 0.001) and cholesterol (p less than 0.001). Triglyceride associated with very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) increased (p less than 0.01), cholesterol in VLDL and LDL increased (p less than 0.01), and levels of HDL cholesterol decreased (p less than 0.01). There were changes in indices of liver function, with increased levels of gamma-glutamyltransferase (GGT) (p less than 0.01), alkaline phosphatase (ALP) (p less than 0.01) and aspartate aminotransferase (AST) (p less than 0.01), and decreased bilirubin levels (p less than 0.05). Although levels of thyroxine and triiodothyronine were lower after treatment (p less than 0.05), there were no changes in basal levels of thyroid-stimulating hormone (TSH), luteinizing hormone (LH) or follicle-stimulating hormone (FSH), and responses to thyrotrophin releasing hormone (TRH) and luteinizing hormone releasing hormone (LHRH) were unchanged. These changes may partially be explained by induction of hepatic microsomal enzymes by isotretinoin.
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PMID:Effects of isotretinoin on serum lipids and lipoproteins, liver and thyroid function. 623 29

Female Sprague-Dawley rats were fed diets containing 0, 0.01, 0.1, or 1.0 mg/kg 3,3',4,4',5,5'-hexabromobiphenyl (345-HBB) for 140 days after a 70% partial hepatectomy and diethylnitrosamine administration (10 mg/kg body weight) to determine if 345-HBB had tumor-promoting ability in a two-stage hepatocarcinogenesis assay. Tumor-promoting ability was assessed by measuring enzyme-altered foci exhibiting gamma-glutamyl transpeptidase activity. Enhancement of enzyme-altered foci occurred only at a dietary concentration of 345-HBB (1.0 mg/kg) that was toxic. The toxic effects were decreased body weight gain, involution of the thymus, increased liver weight, histologic and ultrastructural alterations of the liver, and elevated serum concentrations of aspartate aminotransferase. 345-HBB is a strict 3-methylcholanthrene (MC) type of hepatic microsomal drug metabolizing enzyme inducer and caused a dose-related increase of cytochrome P-450. 345-HBB, at a dietary concentration of 0.1 mg/kg, caused a physiologic response in rats as determined by induction of hepatic microsomal drug metabolizing enzymes, but there was minimal evidence of toxicity and no evidence of tumor-promoting ability. Results indicate that there can be induction of MC type of hepatic microsomal drug-metabolizing enzymes without toxicity or tumor-promoting ability and that the tumor-promoting ability of 345-HBB was most likely the result of hepatic degeneration and necrosis. This finding is in contrast to previous studies in which a closely related congener, 2,2',4,4',5,5'-hexabromobiphenyl, enhanced the development of enzyme-altered foci at dietary concentrations that were not hepatotoxic.
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PMID:Hepatic tumor-promoting ability of 3,3',4,4',5,5'-hexabromobiphenyl: the interrelationship between toxicity, induction of hepatic microsomal drug metabolizing enzymes, and tumor-promoting ability. 631 5

For 70 days two groups of 10-week gilts were given feed supplemented with PCB commercial mixture of Czechoslovak make (Delor 105), at the doses of 10 and 50 mg. .kg-1 of feed. Over the experimental period, animals were administered 1000 mg or 5000 mg of PCB mixture. During the experimental period the levels of glucose, cholesterol, urea, total protein, vitamin A, calcium, inorganic phosphorus and the activities of AF, ALT and AST enzymes were determined twice. At the end of this experiment the aniline hydroxylase activity in microsomal fractions of liver was determined and pronounced induction effect of PCB on the enzymatic system was observed. Out of the studied metabolic parameters of blood plasma, the decrease in vitamin A level was significant.
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PMID:[The effect of polychlorinated biphenyls (PCB) on liver aniline hydroxylase activity and on certain metabolic parameters in the blood of pigs]. 642 Sep 73

Health conditions were evaluated in 80 electrical workers exposed for many years to polychlorinated biphenyl (PCB) mixtures with a 42% mean chlorine content, who had blood PCB concentrations from 41 to 1319 micrograms/kg. The clinical study was based on personal history data, physical examination, and laboratory tests (red cell and leukocyte count; determination of haemoglobin, packed cell volume, bilirubin, serum protein electrophoretic fractions, pseudocholinesterase, AST, ALT, GGT, and OCT). Fifteen workers were found to have skin diseases--chloracne (4), folliculitis (4), oil dermatitis (1), juvenile acne (1), and dermatitis due to irritative or allergic agents (5). Sixteen workers showed more or less pronounced hepatic involvement, consisting most often of hepatomegaly with an increase in serum GGT, AST, ALT, and OCT values. In two workers bleeding cavernous haemangiomas were discovered, in one case associated with chronic myelocytic leukaemia. All the workers with chloracne were employed on electric capacitor impregnation with PCBs, and no definite association was found between chloracne and blood PCB concentrations. Conversely, a significant positive association was found between the abnormal liver findings and blood PCB concentrations, particularly trichlorobiphenyl blood concentrations. The abnormal hepatic findings observed are similar to those reported in experimental animals given PCBs, and in some workers such findings should probably be considered as clinical signs of hepatic microsomal enzyme induction.
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PMID:Occupational exposure to polychlorinated biphenyls in electrical workers. II. Health effects. 645 Dec 37


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