Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.4.1.2 (glutamate dehydrogenase)
 4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isolated proximal tubular (PT) and distal tubular (DT) cells from rat kidney were cultured for up to 9 days under serum-free, hormonally-defined conditions on 35-mm polystyrene culture dishes. Several hormonal and growth factor supplements were assessed for their ability to promote growth (increased protein and DNA content) and stability of differentiated phenotype (high activities of gamma-glutamyltransferase and alkaline phosphatase as brush-border membrane markers in PT cells; maintenance of high activities of glutamate dehydrogenase as a mitochondrial marker in both PT and DT cells; maintenance of low and high activities of lactate dehydrogenase in PT and DT cells, respectively; expression of cytokeratins). Basal supplemented media (DMEM/F12, 1:1 v/v) contained insulin, hydrocortisone, epidermal growth factor, sodium selenite and transferrin as supplements. Additionally, triiodothyronine selectively promoted growth and stability of differentiated phenotype in PT cells and thyrocalcitonin selectively promoted growth and stability of differentiated phenotype in DT cells. On Day 3 of primary culture, PT and DT cells were incubated for up to 8 h with either tert-butyl hydroperoxide (tBH; 0.5-10 mM), methyl vinyl ketone (MVK; 1-10 mM), or p-aminophenol (PAP; 1-10 mM) and cellular injury, as assessed by cellular release of lactate dehydrogenase, was determined. DT cells were significantly more susceptible to injury from both tBH and MVK, but the two cell populations were equally susceptible to injury from PAP, which is the same susceptibility pattern seen in freshly isolated cells. These results suggest that primary cultures of rat renal PT and DT cells reflect similar biochemical properties as freshly isolated cells and are, therefore, useful models for study of chemically induced injury.
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PMID:Susceptibility of primary cultures of proximal tubular and distal tubular cells from rat kidney to chemically induced toxicity. 854 48

To date, no attempt has been made to study alterations occurring in the amino acid profile in chronic models of thioacetamide-induced liver cirrhosis. In this work, changes in serum amino acids and proteins in rats with thioacetamide-induced liver cirrhosis are reported, together with changes in enzyme activities in the liver and serum. Seventeen female Wistar rats were used. Eight rats were given 300 mg thioacetamide/l in drinking water for 4 months and nine rats were given water ad libitum during the same time-period. Significant increases in glycine, alanine, serine, methionine, glutamate, ornithine, phenylalanine, tyrosine, histidine and proline were observed in rats with the resulting experimental liver cirrhosis. Threonine, taurine, glutamine, lysine and citrulline tended to increase while isoleucine, leucine, aspartate, arginine and tryptophan tended to decrease. Total and nonessential amino acids increased significantly in cirrhotic animals. Total essential and aromatic amino acids tended to increase in the thioacetamide-treated group, whereas branched chain amino acids tended to decrease in the same group. Regarding serum proteins, a decrease in albumin concentration in the thioacetamide-treated animals was the only change detected. The liver enzyme activities under observation (aspartate and alanine aminotransferases, glutamate dehydrogenase and threonine deaminase) were lower in the thioacetamide group. Decreases were significant for both transaminases and threonine deaminase. Results for serum activities showed that transaminases did not change in thioacetamide-treated rats in comparison with controls. In contrast, alkaline phosphatase rose dramatically in cirrhotic rats. We conclude that the serum amino acid pattern in this chronic model of liver cirrhosis resembles in part that of the corresponding human disease.
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PMID:Serum amino acid changes in rats with thioacetamide-induced liver cirrhosis. 857 92

Alpha 1-Antitrypsin deficiency predisposes to pulmonary emphysema, liver cirrhosis and hepatocellular carcinoma. Anecdotal evidence and a large autopsy study suggest that severe lung and liver disease rarely coexist in the same subject, but this has not been studied in patients. Therefore we investigated 27 patients with severe alpha 1-deficiency (Pi ZZ) and pulmonary emphysema for signs of liver disease and impaired hepatic function. A subgroup of 7 patients underwent quantitative liver function tests. On physical examination or ultrasonography, cirrhosis or tumor was not suspected in any patient. Conventional liver function tests were completely normal in 17 patients. Elevated serum activities of gamma-glutamyltranspeptidase and/or aminotransferases were seen in 10 patients. In some, the elevation was only marginal and in none more than twice normal. The serum bilirubin concentration and activity of alkaline phosphatase were increased in 1 patient. Serum protein, albumin, fibrinogen, antithrombin III, alpha 1-fetoprotein concentrations, serum activities of cholinesterase and glutamate dehydrogenase, activated partial thromboplastin time and prothrombin time were normal in all patients. The indocyanine green half-life was abnormal only in 1 of 6 patients, suggesting that hepatic blood flow was not impaired in the study group. However, the lidocaine half-life and galactose elimination capacity, parameters of hepatic metabolization, were impaired in 4 and 6 of 7 patients, respectively. We conclude that liver disease or impaired liver function is not a clinically relevant problem in most patients with pulmonary emphysema due to alpha 1-antitrypsin deficiency. But results of quantitative liver function tests, although performed in only a small group of patients, suggest that hepatic metabolization might be impaired even in those patients who present with pulmonary disease.
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PMID:Liver function in patients with pulmonary emphysema due to severe alpha-1-antitrypsin deficiency (Pi ZZ). 873 89

Ten scientific organizations formed a joint international committee to provide expert recommendations for clinical pathology testing of laboratory animal species used in regulated toxicity and safety studies. For repeated-dose studies in rodent species, clinical pathology testing is necessary at study termination. Interim study testing may not be necessary in long-duration studies provided that it has been done in short-duration studies using dose levels not substantially lower than those used in the long-duration studies. For repeated-dose studies in nonrodent species, clinical pathology testing is recommended at study termination and at least once at an earlier interval. For studies of 2 to 6 weeks in duration in nonrodent species, testing is also recommended within 7 days of initiation of dosing, unless it compromises the health of the animals. If a study contains recovery groups, clinical pathology testing at study termination is recommended. The core hematology tests recommended are total leukocyte (white blood cell) count, absolute differential leukocyte count, erythrocyte (red blood cell) count, evaluation of red blood cell morphology, platelet (thrombocyte) count, hemoglobin concentration, hematocrit (or packed cell volume), mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. In the absence of automated reticulocyte counting capabilities, blood smears from each animal should be prepared for reticulocyte counts. Bone marrow cytology slides should be prepared from each animal at termination. Prothrombin time and activated partial thromboplastin time (or appropriate alternatives) and platelet count are the minimum recommended laboratory tests of hemostasis. The core clinical chemistry tests recommended are glucose, urea nitrogen, creatinine, total protein, albumin, calculated globulin, calcium, sodium, potassium, total cholesterol, and appropriate hepatocellular and hepatobiliary tests. For hepatocellular evaluation, measurement of a minimum of two scientifically appropriate blood tests is recommended, e.g., alanine aminotransferase, aspartate aminotransferase, sorbitol dehydrogenase, glutamate dehydrogenase, or total bile acids. For hepatobiliary evaluation, measurement of a minimum of two scientifically appropriate blood tests is recommended, e.g., alkaline phosphatase, gamma glutamyltransferase, 5' -nucleotidase, total bilirubin, or total bile acids. Urinalysis should be conducted at least once during a study. For routine urinalysis, an overnight collection (approximately 16 hr) is recommended. It is recommended that the core tests should include an assessment of urine appearance (color and turbidity), volume, specific gravity or osmolality, pH, and either the quantitative or semiquantitative determination of total protein and glucose. For carcinogenicity studies, only blood smears should be made from unscheduled sacrifices (decedents) and at study termination to aid in the identification and differentiation of hematopoietic neoplasia.
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PMID:Harmonization of animal clinical pathology testing in toxicity and safety studies. The Joint Scientific Committee for International Harmonization of Clinical Pathology Testing. 874 16

Twenty-three male lambs were fed 2.5 ppm of aflatoxin for 21 days. Thirteen lambs constituted the control group. Twelve lambs given toxin and six from the control group were killed at 21 days. The remaining animals were killed 8 days later. To determine haematological and biochemical parameters, samples of blood were obtained at 0, 7, 14 and 21 days of exposure and at 1, 2, 4 and 8 days after exposure. The most sensitive indicator of intoxication was the reduction in body weight (17 +/- 2.2 kg-1 body wt. in intoxicated lambs and 19.2 +/- 1.8 kg-1 body wt. in the control group: P >> 0.01) and in the average daily weight gain (133 +/- 79 g day-1 in the intoxicated group and 254 +/- 105 g day-1 in the control group; P >> 0.001) from the 14th day onwards. Lambs fed with aflatoxins had relatively smaller liver weights and higher kidney and spleen weights than lambs from the control group. Feeding aflatoxins increased the erythrocyte count and the mean corpuscular haemoglobin concentration and decreased the mean corpuscular volume and mean corpuscular haemoglobin values. An elevation of the levels of globulins with an increase of the beta and gamma fractions and no variation in total protein and albumin was observed in lambs fed on aflatoxins. Urea levels and the alkaline phosphatase and glutamate dehydrogenase enzymatic activities decreased as a consequence of intoxication, whereas gamma-glutamyl transferase was increased. During the clearance period, haematological values regressed towards basal values, but biochemical parameters remained unchanged. These results suggest that lambs are sensitive to the toxic effects of the aflatoxins and that the determination of zootechnical parameters is a better aid to the diagnosis of intoxication than haematological or biochemical analyses.
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PMID:Alterations in the performance, haematology and clinical biochemistry of growing lambs fed with aflatoxin in the diet. 882 81

Seeds of Apium graveolens L. (Apiaceae) and Hygrophila auriculata (K. Schum.) Heine (Syn. Astercantha auriculata Nees, Acanthaceae) are used in Indian systems of medicine for the treatment of liver ailments. The antihepatotoxic effect of methanolic extracts of the seeds of these two plants was studied on rat liver damage induced by a single dose of paracetamol (3 g/kg p.o.) or thioacetamide (100 mg/kg, s.c.) by monitoring several liver function tests, viz. serum transaminases (SGOT and SGPT), alkaline phosphatase, sorbitol dehydrogenase, glutamate dehydrogenase and bilirubin in serum. Furthermore, hepatic tissues were processed for assay of triglycerides and histopathological alterations simultaneously. A significant hepatoprotective activity of the methanolic extract of the seeds of both the plants was reported.
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PMID:Hepatoprotective activity of Apium graveolens and Hygrophila auriculata against paracetamol and thioacetamide intoxication in rats. 882 36

Experimental, subclinical acidosis was induced by oral administration of sacharose during the last 2 months of pregnancy in 15 cows. Seven cows and their newborn calves were used as a control group. The liver enzyme activities in the serum and the blood acid-base status were determined in the 15 calves from the cows in the experimental group. Mannitol was administered orally to 8 calves from the experimental group to induce osmotic diarrhoea. It was concluded that subclinical acidosis in pregnant cows alters the biochemical liver profile of their newborn calves, affecting the aspartate aminotransferase, alanine transaminase, beta glucuronidase, glutamate dehydrogenase and bilirubin activities in the serum, which are associated with oedematous changes to the hepatocytes. Diarrhoea was accompanied by an increase in the alkaline phosphatase and gammaglutamyl transferase activities and a decrease in the total protein concentration in the serum. These changes were apparently related to the numerous necrotic foci in the liver and the proliferation of the Kuppfer cells. It would appear from these results that the liver damage in the newborn calves was associated with the subclinical, metabolic acidosis in their dams and that osmotic diarrhoea occurring in the neonatal period additionally impaired the liver function.
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PMID:Changes in the profile of liver enzymes in newborn calves induced by experimental, subclinical acidosis in pregnant cows and osmotic diarrhoea. 886 78

The consumption of plants containing the diterpenoid atractyloside (ATR) causes selective proximal tubule injury, renal failure and death in humans. We have compared the effects of ATR in freshly isolated renal proximal tubules and glomeruli from rat and also in cell lines: NRK, derived from the proximal tubules, and MDBK and MDCK more closely representing the distal nephron. The effects of ATR (10-500 microM) on proximal tubules and glomeruli were assessed by changes in lipid peroxidation, de novo protein synthesis and the leakage of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glutamate dehydrogenase (GDH) and N-acetyl-beta-D-glucosaminidase (NAG). The susceptibility of NRK, MDBK and MDCK cell lines to ATR was assessed by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, measuring mitochondrial reduction. Enzyme leakage was the most sensitive of the markers of cell injury in fresh fragments and ranked LDH > GDH > ALP > NAG in proximal tubules. As little as 20 microM ATR caused significant enzyme leakage from proximal tubules, but there were no increases in enzyme leakage from glomeruli at concentrations < and = 500 microM ATR. De novo protein synthesis was only inhibited 50% at ATR concentration > 5 mM in the proximal tubules, but there were no effects in glomeruli. Malondialdehyde production was significantly elevated at 1 mM ATR for proximal tubules, and 500 microM for glomeruli. NRK cells were sensitive to ATR (IC50, 120 microM), but MDBK or MDCK cells were unaffected by < and = 1 mM of this diterpenoid. Both freshly isolated fragments and continuous cell lines representing the proximal tubules are more sensitive to ATR than either glomeruli or cells representing the distal nephron. These data also show that protein synthesis is a less specific and sensitive measure of ATR cytotoxicity than enzyme leakage in fragments. MTT reduction to formazan was the most sensitive in the NRK cell line. The low levels of lipid peroxidation products in proximal tubular fragments or sensitive renal cell lines at toxic levels of ATR suggest that oxidative injury is not a key mechanism.
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PMID:Selective cytotoxicity associated with in vitro exposure of fresh rat renal fragments and continuous cell lines to atractyloside. 901 May 90

A hyperthermophilic, anaerobic archaeon was isolated from hydrothermal fluid samples obtained at the Okinawa Trough vents in the NE Pacific Ocean, at a depth of 1395m. The strain is obligately heterotrophic, and utilizes complex proteinaceous media (peptone, tryptone, or yeast extract), or a 21-amino-acid mixture supplemented with vitamins, as growth substrates. Sulfur greatly enhances growth. The cells are irregular cocci with a tuft of flagella, growing optimally at 98 degrees C (maximum growth temperature 102 degrees C), but capable of prolonged survival at 105 degrees C. Optimum growth was at pH 7 (range 5-8) and NaCl concentration 2.4% (range 1%-5%). Tryptophan was required for growth, in contrast to the closely related strains Pyrococcus furiosus and P. abyssi. Thin sections of the cell, viewed by transmission electron microscopy, revealed a periplasmic space similar in appearance to the envelope of P. furiosus. The predominant cell membrane component was tetraether lipid, with minor amounts of diether lipids. Treatment of the cells by mild osmotic shock released an extract that contained a Zn(2+)-dependent alkaline phosphatase. Phylogenetic analysis of the sequences encoding 16S rRNA and glutamate dehydrogenase places the isolate with certainty within the genus Pyrococcus although there is relatively low DNA-DNA hybridization (< 63%) with described species of this genus. Based on the reported results, we propose a new species, to be named Pyrococcus horikoshii sp.nov.
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PMID:Pyrococcus horikoshii sp. nov., a hyperthermophilic archaeon isolated from a hydrothermal vent at the Okinawa Trough. 967 87

Severe iron deficiency results in complex systemic disorders e.g., including metabolism of energy and minerals. To investigate whether also moderate iron depletion may alter the activities of citric cycle enzymes and the cytochrome oxidase, the trace element status, and serum enzymes indicative of cell damage, this experiment was carried out with rats supplied with sub-optimal iron (9, 13 and 18 mg iron per kg diet) over a total of 5 weeks. The study included 3 pair-fed groups and an ad libitum group, fed with 50 mg iron/kg diet. All iron-restricted rats were classified as iron-deficient on the basis of reduced iron concentrations in body and iron-depending blood parameters. Body weight gain and catalase activity in kidney were lowered in rats receiving the lowest dietary iron level, exclusively. Rats fed 9 and 13 mg iron per kg diet had nearly 6- and 3-fold, respectively higher platelet counts in blood than their corresponding pair-fed controls. The activities of transaminases ASAT and ALAT, alkaline phosphatase, glutamate dehydrogenase and lactate dehydrogenase in serum which are indicative of cell damage were also markedly influenced by moderate dietary iron restriction, in which the enzyme levels in serum increased with intensifying iron depletion. Although, moderate iron restriction to young male rats was associated with marked alterations in iron status and serum enzymes, the activities of tricarboxylic acid cycle enzymes including malic dehydrogenase, fumarase, and isocitric dehydrogenase as well as cytochrome oxidase in liver remained largely unaffected. Only hepatic aconitase showed a somewhat reduction with iron depletion. Moreover, iron restriction was also accompanied with an accumulation of copper in liver which was significant for rats fed 9 and 13 mg iron per kg diet, whereas zinc status remained completely unaffected by moderate iron deficiency. It can be concluded, that a short-term moderate iron deficiency with ranging hemoglobin concentrations from 66 and 121 g/L, was accompanied with altered platelet counts, serum enzyme activities indicative of cell damage, and hepatic copper concentrations, but the activities of the tricarboxylic acid cycle enzymes and cytochrome oxidase in liver remained largely unaffected.
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PMID:Effect of different degrees of moderate iron deficiency on the activities of tricarboxylic acid cycle enzymes, and the cytochrome oxidase, and the iron, copper, and zinc concentrations in rat tissues. 980 Mar 17


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