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)

Treatment of rats with nifurtimox, a nitrofuran derivative widely used for the treatment of Chagas' disease, induced a time- and dose-dependent depletion of liver glutathione, maximal effects being obtained with 200 mg nifurtimox/kg body weight. Extra release of both oxidized (GSSG) and reduced (GSH) glutathione into bile contributed to this depletion. Glutathione excretion into bile accounted for only part of liver glutathione loss, thus indicating that, in addition to the GSH-peroxidase reaction (resulting in GSSG generation), other glutathione-related processes were involved in nifurtimox detoxification. Bile flow, bile salt excretion, liver lipid conjugated diene content, liver glutathione reductase and glutathione peroxidase activities, and serum alanine aminotransferase (ALAT) activity were not affected by the nifurtimox treatment, thus ruling out widespread damage of the liver cell by nifurtimox. Nevertheless, the extra GSH release in the nifurtimox-treated rats may indicate an alteration of the hepatocyte membrane.
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PMID:Increased biliary secretion and loss of hepatic glutathione in rat liver after nifurtimox treatment. 684 98

The activities of 13 liver and 6 brain enzymes were studied in 7-12 week old CD2F1 male mice that had been fed ad libitum and standardized either to 12 hours of light (0600-1800) alternating with 12 hours of darkness (1800-0600) (LD12:12); or to a reversed light-dark cycle (darkness 0600-1800; light 1800-0600) (DL12:12). Three separate studies were performed on two different days; in each experiment, subgroups of 14 animals were sacrificed at 3-hour intervals. Livers were assayed for: isocitrate dehydrogenase, glutamate dehydrogenase, lactate dehydrogenase, alcohol dehydrogenase, glutathione reductase, glyoxylate reductase, L-alanine aminotransferase, glutamate oxalacetate transaminase, pyruvate decarboxylase, fructose-1-phosphate aldolase, fructose diphosphate aldolase, fructose 1,6-diphosphatase, and fatty acid synthetase. Brains were assayed for phosphoglucose isomerase, adenosine triphosphatase, creatine phosphokinase, pyruvate kinase, adenylate kinase, and malate dehydrogenase. All 19 enzymes demonstrated a prominent circadian rhythm in at least one experiment. Moreover, each rhythmic variable showed a statistically significant fit to a 24-hour cosine (sine) curve by the method of least squares. In general, peak activities of the liver enzymes analyzed were associated with the beginning of the dark cycle and initiation of the animal's activity, while the group of brain enzymes had peak activities which occurred at the beginning of the animals' rest span and were near the beginning of the light cycle. The phasing of each of the rhythms could be reversed within a two-week span after reversing the environmental light-dark cycle 180 degrees.
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PMID:Circadian organization of thirteen liver and six brain enzymes of the mouse. 731 49

A study was conducted to assess the nutritional status of riboflavin and vitamin B6 of the elderly in Central Kentucky. Elderly subjects aged 60 to 95, including 42 men and 77 women, were randomly selected: 41 from six nursing homes and 78 from private residences. Blood and urine samples were collected for analysis. Riboflavin and vitamin B6 status were assessed by using glutathione reductase activation coefficient and glutamic-pyruvic transaminase activation coefficient, respectively. Glutathione reductase activation coefficients ranged from 0.88 to 1.89 with a mean +/- SD of 1.23 +/- 0.22, and were not significantly correlated with the urinary excretion of riboflavin. Glutamic-pyruvic transaminase activation coefficients ranged from 0.86 to 1.50 with a mean +/- SD of 1.16 +/- 0.14, and were negatively correlated with urinary excretion of 4-pyridoxic acid. Riboflavin deficiency was found in 34.2 percent of the institutionalized and 27.7 percent of the non-institutionalized subjects, while vitamin B6 deficiency was found in 56.6 percent of the institutionalized and 43.5 percent of the non-institutionalized subjects studied. The institutionalized elderly showed significantly poorer riboflavin status (P less than 0.01) and vitamin B6 status (P less than 0.05) than the non-institutionalized elderly. Aging was associated with a significant decline in both riboflavin (P less than 0.01) and vitamin B6 status (P less than 0.05).
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PMID:Biochemical evaluation of riboflavin and vitamin B6 status of institutionalized and non-institutionalized elderly in Central Kentucky. 731 23

Serum activity of glutathione reductase (GR), glucose phosphate isomerase (GPI), aspartate aminotransferase (AST), alanine aminotransferase (ALT) phosphate alkaline (PAL), and gamma-glutamyl transferase (GGT) was studied in 142 patients, in all serum bilirubin was more than 2 mg/dl. Distribution was as follows; 68 cirrhosis of the liver; 27 acute hepatitis; 31 benign extra-hepatic biliary obstruction; and 16 neoplastic obstruction of the biliary tract without liver metastasis. Fifty-three healthy volunteer blood donors were used as the control group. Mean values for GR activity in our patients were significantly higher than those for the control group, although less so in benign obstruction (p less than 0.01) than in those with acute hepatitis (p less than 0.001), cirrhosis (p less than 0.01) and neoplasic biliary obstruction (p less than 0.001). The GPI values were higher than the control groups in patients with acute hepatitis (p less than 0.001) and obstructive neoplastic jaundice (p less than 0.02). In cases with cirrhosis, 87% presented slightly higher values of GR, while GPI was within normal levels in 93 % of all cases. In patients with acute hepatitis, 92% showed a definite increase in GPI and GR values. In 71% of those with benign biliary obstruction levels for both enzymes were normal, as they were in only 6% of those with obstructive neoplastic jaundice. These findings are statistically significant in all cases and of diagnostic value in establishing a differential enzymatic diagnosis in patients presenting with clinical and biological patterns of cholestasis.
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PMID:[Determination of serum activity of glucose phosphate isomerase and glutathione reductase in intra and extra hepatic cholestasis.(author's transl)]. 732 37

Cisplatin, a nephrotoxic chemotherapeutic agent, was injected into Sprague Dawley rats, alone or together with cysteine, vitamin E and clonidine. The effects on erythrocyte fragility, serum composition, and kidney and liver enzymes were studied. Cisplatin was administered as two i.p. injections (6 mg/kg body weight) at an interval of 120 hours. The animals were sacrificed 24 hours after the second injection. Erythrocytes were prepared from blood collection with anticoagulant. Serum was prepared from clotted blood, collected without anticoagulant. Kidneys and liver were removed and homogenized, and a supernatant prepared by high speed centrifugation. In cisplatin-treated rats, the serum activities of aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase and alkaline phosphatase were significantly decreased, whereas the activities of isocitric dehydrogenase and glutathione reductase were increased. Also, concentrations of blood urea nitrogen, creatinine, total lipids and magnesium increased while albumin and glucose decreased. Mean osmotic fragility of erythrocytes from cisplatin-treated rats was decreased, while the haematocrit was increased. In the liver, the only change seen was an increased activity of isocitric dehydrogenase. Much greater changes were found in the kidneys, with increased activity of glucose-6-phosphate dehydrogenase and decreased activities of aspartate and alanine aminotransferases, alkaline phosphatase, malic dehydrogenase, sorbitol dehydrogenase and gamma-glutamyltransferase, as well as a decreased phosphorylation to oxidation ratio in the mitochondria, indicating reduced adenosine triphosphate production. Administration of cysteine and vitamin E together with cisplatin partially reversed the uraemia and many of the biochemical changes induced by cisplatin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in serum, liver and kidneys of cisplatin-treated rats; effects of antioxidants. 788 81

Chloroform (CHCl3) is widely used in the manufacture of drugs, cosmetics, plastics and cleaning agents. It is also found in chlorinated drinking water. This study was designed to investigate the toxic effect of CHCl3 on isolated male rat hepatocytes using several toxicity parameters. The hepatocytes were isolated by a collagenase perfusion technique and the cell viability was determined by Trypan blue exclusion. The leakage of cytosolic enzymes such as aspartate transaminase (AST) and alanine transaminase (ALT) after treatment with CHCl3 was measured. Reduced glutathione content (GSH) and its related enzymes, glutathione reductase (GSH-Rx) and glutathione peroxidase (GSH-Px), were also evaluated to study the effect of CHCl3 on hepatocytes. Exposure to 100 and 1000 ppm CHCl3 results in a significant decrease in cell after 30 min incubation. However, the effect of 1 and 10 ppm concentrations was observed at 60 min incubation. AST leakage was significantly increased in all treatment groups, while ALT was significantly increased at 100 and 1000 ppm CHCl3 after 60 and 30 min, respectively. As early as 15 min, GSH was decreased significantly at 1000 ppm, but at 100 and 10 ppm CHCl3 the decrease in GSH began after 30 and 120 min, respectively. GSH-Px activity did not changed. However, the activity of GSH-Rx was significantly decreased at 1000 ppm CHCl3 and at the same time GSH content was decreased. The data indicate that the toxic effect of CHCl3 was dose- and time-dependent. The degree of GSH depletion correlated with increased cytotoxicity and decreased GSH-Rx activity due to CHCl3.
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PMID:The mechanism of chloroform toxicity in isolated rat hepatocytes. 835 69

Mercury is the major component of dental amalgam restorative material, which typically has 50% pure elemental mercury. It is also used in some skin creams, and in the manufacturing of plastic, drugs and fungicides. The present study was designed to investigate the toxicity of methyl mercury (MeHg+) on isolated rat hepatocytes using several toxicity parameters. The hepatocytes were isolated by a collagenase perfusion technique and were incubated with different concentrations of MeHg+ (0.1-100 ppm) for 2 h. Through the incubation period the viability was determined by Trypan blue exclusion. Reduced glutathione (GSH) content and its enzymes, glutathione peroxidase (GSH-PX) and glutathione reductase (GSH-RX) were measured. Leakage of enzymes such as aspartate transaminase (AST), and alanine transaminase (ALT) were determined. The cell viability was reduced significantly after 1 h incubation when 0.1 and 1 ppm MeHg+ were applied. The decrease in the cell viability was dose- and time-dependent. A depletion of GSH content was observed with 100 ppm MeHg+ after 30 min of incubation. A significant decrease in GSH-RX was observed with 100 ppm during 15 and 30 min of incubation, while 10 ppm of MeHg+ significantly increased ALT leakage after 60 min. However, there was a significant increase in AST leakage with 100 ppm only. The present investigation indicates that the toxic effect of MeHg+ is most likely cytosolic enzyme related.
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PMID:The mechanism of methyl mercury toxicity in isolated rat hepatocytes. 835 70

Chronic liver damage induced by thioacetamide (TAM) was accompanied by changes in the expression of genes related to growth (beta-actin) and function (albumin and haptoglobin) of the liver. Their messenger RNA (mRNA) levels increased during the first days after TAM administration, but 4 to 7 days after prolonged treatment with this drug, liver gene expression was considerable decreased. TAM-induced changes in albumin and beta-actin mRNA levels were prevented by cotreatment with S-adenosyl-L-methionine (SAM). We have investigated the possible involvement of glutathione in the protective mechanism of SAM. Firstly, we found that TAM treatment in the rat induced changes in liver glutathione disulfide (GSSG) levels, with a concomitant increase in the glutathione reductase enzymatic activity, these changes being abolished when animals were cotreated with TAM and SAM. Secondly, when rats were pretreated with buthionine sulfoximine (BSO), a glutathione synthesis inhibitor, before thioacetamide administration, the beneficial effect of SAM on liver gene expression was completely abolished. These results were confirmed by assaying the alanine transaminase serum activity, a parameter of liver injury. TAM-treated animals had increases in this serum enzyme, this effect being partially blocked by SAM. However, in BSO-pretreated rats, the protective effect of SAM was impaired. Taking together all these results, we propose a glutathione-dependent mechanism in the SAM protection against TAM hepatotoxicity in the rat.
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PMID:Changes in rat liver gene expression induced by thioacetamide: protective role of S-adenosyl-L-methionine by a glutathione-dependent mechanism. 861 42

The influence of r-HuEPO on the activity of erythrocyte transketolase (ETKA), glutathione reductase (GSH) and glutamic-pyruvic transaminase (EGPT) was determined by spectrophotometry. 150 IU/kg BW/week of r-HuEPO was given i.v. during 2 months to 12 predialyzed uremics (PDU). Twenty healthy volunteers (HV) served as controls. GSH and EGPT activity were expressed as a coefficient. ETKA in HV = 2.39 +/- 0.10 and PDU = 1.53 +/- 0.10 mumol/ml/min differed significantly (p < 0.001). GSH in HV = 1.20 +/- 0.09 and PDU = 1.25 +/- 0.07, EGPT in HV = 1.20 +/- 0.10 and PDU = 1.38 +/- 0.11 differed significantly (p < 0.01 and p < 0.001, respectively). After 2 months of r-HuEPO treatment, ETKA, GSH and EGPT rose significantly (p < 0.01). Thus, r-HuEPO increases the activity of enzymes related with the content of vitamins B1, B2 and B6 in uremics.
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PMID:Recombinant human erythropoietin improves enzyme activity in erythrocytes of predialysis uremics. 867 97

The role of oxidative stress as a mechanism of hepatic injury caused by isoniazid (INH) was investigated in young growing rats. The interaction of moderate and severe degree of protein-energy malnutrition (PEM) was also investigated. Hepatic injury was produced by giving 50 mg/kg/day of INH for 2 weeks. Liver showed kupffer cell hyperplasia along with patchy sinusoidal congestion in hematoxylin (H) and eosin (E) staining. However, diffuse microglobules of oil red O' positive fat globules could be demonstrated in frozen sections stained with oil red O'. The concomitant elevation of serum ALT/AST added support to the histopathologic injury. Electronmicroscopic analysis revealed the proliferation of rough endoplasmic reticulum in INH-treated groups. The glutathione and related thiols were decreased significantly by INH both in blood and liver tissues, indicating a decrease in protective mechanism. Glutathione reductase activity was elevated concomitantly in both the tissues. A significant decrease in the activity of glutathione peroxidase and catalase is again indicative of diminished capacity to handle the disposal of hydrogen peroxide (H2O2) and lipid peroxides. All these alterations indicated that the damage to the liver cell could well be operating through the inefficient disposal of superoxides (O-2) and H2O2. A profound decrease in the protective mechanism further aggravated the picture in moderate and severe PEM, which was observed with INH alone.
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PMID:Study of oxidative stress in isoniazid-induced hepatic injury in young rats with and without protein-energy malnutrition. 902 73


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