Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The possible aggravation of liver injury by impaired cellular antioxidant function was investigated. A vitamin E-deficient diet (0.5 mg/kg alpha-tocopherol; control 100 mg/kg) significantly reduced rat liver alpha-tocopherol concentrations after 4 weeks (1.8 +/- 1.7 micrograms/g; control 34.4 +/- 2.4 micrograms/g, p < 0.001). The effects of copper loading (Cu, 3 g/kg diet); galactosamine (GalN, 0.85 g/kg i.p.); or carbon tetrachloride (CCl4, 10 mmol/kg i.p.) were examined. Serum aspartate transaminase activity was elevated slightly by vitamin E deficiency but not by hepatic copper accumulation. In vitamin E-replete (E+) and vitamin E-deficient (E-) rats, GalN or CCl4 caused a large and comparable elevation in serum AST and OCT activity. This effect on AST was markedly reduced by copper loading in vitamin E replete (E+) rats, but in E(-) rats copper had significantly less protective effect. Copper also diminished the OCT response to GalN in E+, though not E-, rats. A significant rise in total hepatic alpha-tocopherol content followed administration of GalN or CCl4 in both normocupric and copper-laden E(-) rats. Thus alpha-tocopherol deficiency (a) was not hepatotoxic per se; (b) failed to potentiate the toxicity of copper, GalN or CCL4; but (c) partially abolished the protection by copper against toxin-induced liver injury. Retention of hepatic alpha-tocopherol after liver damage may partly explain low serum vitamin E levels seen in clinical liver disease.
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PMID:Alpha-tocopherol deficiency fails to aggravate toxic liver injury but liver injury causes alpha-tocopherol retention. 148 10

Two trials were conducted to determine the effect of monensin in broiler litter on sheep receiving the broiler litter in their diets. Broiler litter from chickens fed monensin as a coccidiostat, and from chickens receiving no coccidiostat, was included at a level of 30% in 2 sheep diets. In a further 2 treatments, monensin (15 mg kg-1) was added to each of the 2 diets to give a 2x2 factorial experimental design. In the first trial, copper (20 mg kg-1 feed) was added to the diets. These lambs were fed individually at a slightly restricted level of intake. No differences between treatments were observed in feed intake, average daily gain or efficiency of feed utilisation or in the concentrations of zinc, iron and manganese in the liver, glutathione peroxidase in erythrocytes and creatine kinase concentrations in the plasma. Hepatic copper content and copper retention in the livers of the sheep receiving the added monensin were significantly higher (P less than 0.05 and less than 0.01 respectively) than in those not receiving added monensin. The aspartate transaminase and alkaline phosphatase concentrations in the plasma of these sheep were also higher (P less than 0.05) than in those not consuming added monensin. In the second trial, the lambs were group-fed according to treatment and received the diets on an ad lib basis. The mean intakes of the groups receiving the diets with the added monensin, were lower than the intakes by the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of monensin and its metabolites in broiler litter on sheep consuming the broiler litter. 177 Apr 87

These studies were designed to determine if macular mutant mouse, which is a proposed animal model of Menkes' kinky-hair disease, is sensitive to the acute toxic effect of Cu as compared to normal and heterozygote mice. Single sc injection of Cu were administered to 6- to 8-day-old mice, and mortalities were recorded for 30 days. The copper treatment at high doses (12 to 25 mg Cu/kg) was very toxic to mutant mice as compared to normal mice, and almost all mutant mice died within 10 days after injection. The effect of Cu toxicity on heterozygote mice was intermediate. The LD50 values 3 days after injection of Cu were 29.5 mg Cu/kg for normal mice, 23.5 mg Cu/kg for heterozygote mice, and 15.5 mg Cu/kg for mutant mice. In Cu-injected mutant mice (11 and 18 mg Cu/kg), significant elevations in serum aspartate aminotransferase and lactate dehydrogenase activity occurred as compared to Cu-injected normal and heterozygote mice. However, no significant elevations in serum creatinine and urea nitrogen contents in Cu-injected mutant were observed as compared to normal and heterozygote mouse. No significant differences in hepatic metallothionein(MT) and MT-1 mRNA, and serum ceruloplasmin oxidase activity levels were observed between Cu-injected normal and mutant mouse. These results indicated that macular mutant mice was sensitive to the acute toxic or hepatotoxic effects of Cu as compared to normal and heterozygote mice.
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PMID:Copper-induced toxicity in macular mutant mouse: an animal model for Menkes' kinky-hair disease. 187 75

Establishing a diagnosis of fulminant Wilson's disease can be difficult because Kayser-Fleischer rings may not be present and parameters of copper metabolism, including serum and urinary copper, and serum ceruloplasmin levels are neither specific nor diagnostic. In this study, ratios of both the serum alkaline phosphatase to total bilirubin and aspartate transaminase to alanine transaminase were constructed to evaluate their usefulness in differentiating fulminant hepatic failure caused by Wilson's disease (n = 6) from other etiologies (n = 43). An analysis of the data showed that cutoff values of less than 2.0 for the alkaline phosphatase-total bilirubin ratio and greater than 4.0 for the aspartate transaminase ratio were associated with a diagnosis of fulminant hepatic failure caused by Wilson's disease only (P less than 0.001). The alkaline phosphatase-total bilirubin ratio of less than 2.0 provided 100% sensitivity and specificity in identifying fulminant hepatic failure caused by Wilson's disease from other types of fulminant hepatic failure.
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PMID:Clinical differentiation of fulminant Wilsonian hepatitis from other causes of hepatic failure. 200 14

To examine the role of oxidant damage to subcellular membranes in the pathogenesis of copper hepatotoxicity, the effects of dietary copper overload and varying states of vitamin E on biochemical, histological, and ultrastructural features of rat liver were investigated. Weanling male rats were pair-fed for 8 weeks on diets containing normal or high levels of copper in combination with either deficient, sufficient, or excessive vitamin E. Hepatic microsomes and mitochondria, isolated by differential centrifugation, showed similar enrichment and recovery among all experimental groups. Evidence of in vivo peroxidation of membrane lipids (generation of conjugated dienes and thiobarbituric acid reacting substances) was present in mitochondrial but not microsomal preparations from copper-overloaded rats. Serum aspartate aminotransferase, alanine aminotransferase, and cholylglycine (which were increased in all copper-overloaded rats), as well as mitochondrial thiobarbituric acid-reacting substances, were more elevated in vitamin E-deficient rats. In copper-overloaded rats, liver histology showed changes of acute and chronic hepatocyte injury with mild periportal fibrosis; electron microscopy showed abundant copper-containing lysosomes and dilated cristae of hepatocyte mitochondria, findings similar to those in the liver of humans with copper-overload disorders. These findings suggest that an oxidant injury to hepatocyte mitochondria may be one of the initiating factors in hepatocellular damage that leads to hepatic lesions in copper-overload states in humans.
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PMID:Oxidant injury to hepatic mitochondrial lipids in rats with dietary copper overload. Modification by vitamin E deficiency. 239 27

Three hundred and seventy-three female and 213 male nonalcoholic subjects, aged 60-100 y, who had participated in a nutritional status survey of elderly people in the Boston area were grouped according to usual alcohol intake: 0-4, 5-14, or 15+ g/d. The age- and sex-adjusted mean intake of calories, fat, protein, carbohydrate, and 10 micronutrients and the mean levels of 14 nutrient and 22 nonnutrient biochemical indices were compared for the three categories of alcohol intake. The mean micronutrient intakes were also adjusted for total caloric intake and the mean nutrient biochemical concentrations were also adjusted for the corresponding nutrient intakes. The results suggest that caloric intake and blood concentrations of retinol, iron, ferritin, HDL cholesterol, AST, and ALT increased with increasing alcohol intake whereas folate and phosphorus intakes and blood measures of riboflavin, copper, zinc, urea nitrogen, and creatinine decreased with increasing alcohol intake.
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PMID:Moderate alcohol intake and nutritional status in nonalcoholic elderly subjects. 280 94

Metabolic and hormonal responses of eight adult male collared peccaries (Tayassu tajacu) to an ad libitum diet intake, or 25% of an ad libitum intake, were examined. Blood samples for hematological, serum-biochemical and hormonal profiles were collected at three week intervals during the nine week experiment starting 4 August 1983. Males fed on the restricted diet lost an average of 26% of their body weight during the trial, compared to a slight weight gain for those fed ad libitum. Characteristics of the red and white blood cell populations were not influenced by diet intake, with the exception of mean corpuscular volume, which was consistently lower amongst males fed on the restricted diet. Restricted food intake resulted in significantly elevated serum values for urea nitrogen, urea nitrogen:creatinine, urea index, alpha globulin:beta globulin, gamma globulin:albumin, nonesterified fatty acids, alkaline phosphatase and lactate dehydrogenase isozymes (LD1 and LD2). Restricted food intake resulted in significantly lowered serum values for total alpha globulin, alpha-1 globulin, total beta globulin, beta-1 globulin, beta-2 globulin, glucose, triglycerides, calcium, magnesium, sodium, chloride, copper and triiodothyronine. Serum levels of creatinine, total protein, albumin, alpha-2 globulin, uric acid, total bilirubin, cholesterol, aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase, lactate dehydrogenase, phosphorus, calcium:phosphorus, potassium, iron, zinc and thyroxine were unaffected by diet intake level. Semen evaluation indicated spermatogenesis was not affected by dietary restriction despite reductions in scrotal circumference and ejaculate gel volume. Serum testosterone levels were significantly lower among males fed on the restricted diet after nine weeks. These data suggest male libido might be depressed during poor range conditions, while maintenance of spermatogenesis might permit them to take immediate advantage of improved range conditions. Blood analysis of metabolic and hormonal function can provide useful information for predicting the adult male's nutritional and reproductive condition.
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PMID:Physiological responses of the adult male collared peccary, Tayassu tajacu (Tayassuidae), to severe dietary restriction. 286 11

The prognostic value of the aminoterminal propeptide of type III procollagen (P3NP) was investigated in 63 patients with primary biliary cirrhosis (PBC) followed for up to 87 months. No patient with an initially normal serum P3NP level died during the study; survival was significantly worse with increasing serum P3NP levels. Cox multivariate analysis confirmed that serum P3NP was an independent prognostic variable. Positive correlations were found between serum P3NP and histological stage, pericellular fibrosis, piecemeal necrosis, and serum concentrations of alanine aminotransferase and aspartate aminotransferase. Raised P3NP levels also correlated with the degree of cholestasis as evaluated by serum bilirubin, serum alkaline phosphatase, and copper binding protein deposition in the liver. Serum P3NP is of prognostic value because it reflects the major pathophysiological features of PBC.
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PMID:Type III procollagen peptide: a marker of disease activity and prognosis in primary biliary cirrhosis. 289 70

Copper is believed to be hepatotoxic in Indian Childhood Cirrhosis and Wilson's disease. However, copper-loading causes only minimal hepatic damage in animal models. The hypothesis was therefore proposed that a second hepatic insult may precipitate or perpetuate liver injury in a copper-laden liver. In non-copper-dosed rats CCl4 (10 mmol/kg, i.p.) produced elevated serum AST (809 +/- 298 IU/l, normal 20 +/- 5) and ALT (295 +/- 157 IU/l, normal 6 +/- 1) and extensive liver cell necrosis, portal tract inflammation, fat deposition, and perilobular hepatocyte ballooning. In rats whose liver copper was elevated from 75 +/- 13 to 461 +/- 13 micrograms/g by oral copper supplementation, CCl4 produced much smaller increases in AST (492 +/- 80 IU/l) and ALT (172 +/- 57 IU/l) and mild focal liver cell necrosis. Fat deposition and perilobular vacuolation were not reduced. Prior copper-loading of rats unequivocally protected against the CCl4-induced liver injury. Triglyceride accumulation, however, was apparently unaffected. The possible interactions of copper with prostaglandin-mediated inflammation and with free-radical-induced liver damage are discussed.
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PMID:The effect of carbon tetrachloride on the copper-laden rat liver. 292 91

A prospective, controlled study was undertaken in parturients with normal pregnancy and in parturients with intrahepatic cholestasis of pregnancy (IHC) to assess changes in maternal serum copper and zinc concentrations. Cord serum levels of these trace metals were measured, as well. Copper and zinc were measured by particle-induced X-ray emission (PIXE) analysis on two occasions during pregnancy; and immediately, 5 days and 5 weeks after delivery. Maternal serum copper was significantly higher in the IHC group as compared to the control group at 36-40 weeks of pregnancy and immediately and 5 days after delivery. There were no statistically significant differences between the control and study groups for maternal and cord serum zinc and cord copper concentrations. A positive correlation between maternal serum copper and serum aspartate aminotransferase was observed.
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PMID:Serum copper and zinc concentrations in intrahepatic cholestasis of pregnancy: a controlled study. 301 31


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