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

---

Query: EC:1.4.1.2 (glutamate dehydrogenase)
4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The two conjugates, S-[N-(2-hydroxyethyl)carbamoylmethyl]glutathione (GSAAE), and its corresponding mercapturic derivative N-acetyl-S-[N-(2-hydroxyethyl)carbamoylmethyl]cysteine (NCySAAE) were administered to fasted Sprague-Dawley rats as putative metabolites of vinylidene chloride (VDC). Methylthioacetylaminoethanol (MAAE) was identified in the urine of GSAAE- or NCySAAE-treated rats (0.5-2.0 mmol/kg, i.p.), as well as in the urine of VDC-treated rats (0.5-2.0 mmol/kg, p.o.). The effects of VDC, GSAAE and NCySAAE on the kidney and liver were also examined using aspartate aminotransferase (ASAT). N-acetyl-beta-D-glucosaminidase (NAG) and beta 2-microglobulin (beta 2-m) as urinary parameters of nephrotoxicity, and glutamate dehydrogenase (GLDH), sorbitol dehydrogenase (SDH) and alanine aminotransferase (ALAT) as serum parameters of hepatotoxicity. Unlike treatment with VDC, treatment with both GSAAE and NCySAAE failed to cause kidney and liver toxicity. The results support the hypothesis that MAAE originates from the formation of GSAAE and further metabolization to NCySAAE, and that MAAE excretion does not reveal a pathway of reactive intermediates.
...
PMID:Formation of GSH-derivatives as a pathway for inactive intermediates in vinylidene chloride-treated rats. 900 91

Healthy adult male desert sheep were experimentally infected with Fasciola gigantica, to investigate the influence of experimental fasciolasis on the pharmacokinetics of antipyrine and sulphadimidine. Each animal received 500 metacercariae orally. The experimental infection was confirmed histologically, by detection of Fasciola eggs in faeces and by measuring the activities of the enzymes sorbitol dehydrogenase (SD), glutamate dehydrogenase (GD) and aspartate aminotransferase (AST) in plasma during the course of the disease. Changes in the pharmacokinetics of antipyrine and sulphadimidine were reported in the experimentally infected animals. Significant prolongation of antipyrine half life was observed 16 weeks after infection. The half-life of sulphadimidine was also significantly prolonged 5, 9 and 16 weeks after infection. Clearance of the sulphonamide was decreased significantly 5 and 9 weeks after infection and it regained its pre-infection value 16 weeks after infection.
...
PMID:The effect of experimental fascioliasis on the pharmacokinetics of antipyrine and sulphadimidine in desert sheep. 918 81

Single doses of aflatoxin B1 (2 mg/kg, i.p.) caused significant increases in the activities of tau-glutamyl transpeptidase, 5'-nucleotidase, acid phosphatase and acid ribonuclease, and decreases in the activities of succinate dehydrogenase and glucose-6-phosphatase in liver, after 8 weeks. The level of lipid peroxides, DNA, RNA, and cholesterol increased while glycogen decreased. It also increased the serum level of transaminases, sorbitol dehydrogenase, glutamate dehydrogenase, lactate dehydrogenase, acid phosphatase, alkaline phosphatase, and bilirubin. Oral administration of picroliv (25 mg/kg/day for 15 days), a standardised iridoid glycoside fraction of Picrorhiza kurroa, 6 weeks after aflatoxin B1 toxication, significantly prevented the biochemical changes induced in liver and serum of aflatoxin B1 treated rats. The hepatocurative effect of picroliv and silymarin, a plant based standard hepatoprotective are comparable.
...
PMID:Hepatocurative effect of picroliv and silymarin against aflatoxin B1 induced hepatotoxicity in rats. 1119 26

The diagnostic utility of alpha-glutathione S-transferase (alphaGST) in the assessment of acute hepatotoxicity was compared with a range of markers including alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Rats were given a single oral dose of either alpha-naphthylisothiocynate (AN IT), bromobenzene (BrB). or thioacetamide (TAM) at concentrations previously shown to induce marked hepatotoxicity. The progression of each hepatic lesion was monitored by the measurement of a battery of markers, including alphaGST, in plasma collected at time points ranging from 3 h to 7 days after dosing. alphaGST was seen to increase significantly at 24 h (ANIT/BrB) and 3 h (TAM) postdosing, corresponding with histopathological findings. For each compound, when the degree of insult was most severe, fold increases in alphaGST were greater than those seen with ALT and AST, yet lower than those seen with glutamate dehydrogenase (BrB and ANIT). sorbitol dehydrogenase (TAM), or total bilirubin and bile acids (ANIT). Elevations in alphaGST were also detected no earlier than any other marker. AlphaGST in the rat was shown to be a valid marker of hepatotoxicity; however, its measurement offered no additional information in detecting either the time of onset/recovery or the severity of each type of hepatic injury induced.
...
PMID:Alpha-glutathione S-transferase in the assessment of hepatotoxicity--its diagnostic utility in comparison with other recognized markers in the Wistar Han rat. 1205 54

In a recent study in rats, alanine aminotransferase (ALT), the preferred plasma biomarker of hepatocellular injury in rats, was ineffective at detecting marked hepatic necrosis produced by acetaminophen (Human and Experimental Toxicology 19, 277-83, 2000). In contrast, glutamate dehydrogenase (GLDH) was markedly elevated. Accordingly, these enzymes were comprehensively evaluated as plasma biomarkers of hepatocellular injury in rats using several other models of hepatic injury, including partial hepatectomy and exposure to methapyrilene, dexamethasone, cyproterone, isoniazid, lead nitrate, and Wyeth-14643. Other enzymes also evaluated were aspartate aminotransferase (AST), sorbitol dehydrogenase (SDH), and the hepatobiliary marker alkaline phosphatase (ALP). Compared to plasma ALT increases, plasma GLDH increases were up to 10-fold greater, up to 3-fold more persistent, and occurred at times following hepatocellular injury when plasma ALT was not increased. Plasma GLDH activity was not inhibited by the test compounds, whereas ALT was substantially inhibited by both isoniazid and lead nitrate. While plasma GLDH activity was unaffected by induction, ALT was induced by cyproterone and dexamethasone, and ALP was induced by Wyeth-14643 and partial hepatectomy. GLDH was concluded to be a more effective biomarker of acute hepatic injury than ALT, AST, SDH or ALP in the rat, based primarily on the large increase following hepatocellular injury, prolonged persistence in the blood following injury, high sensitivity for detection of injury (including pre-necrotic injury), high tissue specificity, and lower susceptibility to inhibition or induction.
...
PMID:Advantages of glutamate dehydrogenase as a blood biomarker of acute hepatic injury in rats. 1214 42

Plasma bile acids, plasma amino acids, and the total hepatic pools of aspartate aminotransferase, gamma glutamyltransferase, glutamate dehydrogenase, and sorbitol dehydrogenase were compared in control sheep (Group 1), sheep with subclinical pyrrolizidine alkaloid toxicosis (Group 2), and in sheep with acute hepatocellular necrosis associated with the hemolytic phase of chronic copper poisoning (Group 3). Subclinical pyrrolizidine alkaloid toxicosis was not associated with any changes in bile acid or amino acid status but was associated with a significant decline in the hepatic pools of sorbitol dehydrogenase and aspartate aminotransferase. This observation could not be explained in terms of enzyme leakage from damaged hepatocytes and suggested that pyrrolizidine alkaloids might specifically inhibit hepatocellular enzyme synthesis. Group 3 sheep also had reduced hepatic enzyme pools which were at least partly referable to enzyme leakage from damaged hepatocytes. In these sheep, increases in plasma bile acids were a more sensitive index of hepatic function than were either increased aromatic amino acid concentration or the ratio between branched chain and aromatic amino acids.
...
PMID:Changes in plasma bile acids, plasma amino acids, and hepatic enzyme pools as indices of functional impairment in liver-damaged sheep. 1267 2

Serum enzyme activities of sorbitol dehydrogenase, glutamate dehydrogenase, gamma glutamyltransferase, alkaline phosphatase, aspartic aminotransferase, and creatine kinase, were measured in five clinically normal mixed-breed goats. Tissue activities of these enzymes were also measured in two goats. These basal serum values were then used to determine the response to treatment with carbon tetrachloride (CCl4). The basal value for serum and hepatic tissue sorbitol dehydrogenase were appreciably greater for goats than previously reported for sheep and cattle. The change in the above serum enzymes after CCl4 treatment resembled that in sheep, but the amount of sorbitol dehydrogenase increase was less than that in sheep. This study established basal tissue and serum enzyme activity values and demonstrated the efficacy of the use of changes in serum S.D.H. and G.D.H. activity as indicators of acute hepatopathy in goats.
...
PMID:Serum and tissue enzyme profiles of goats. 1603 Nov 71

The goals of the present study were to determine whether the infusion of a glucose solution into the portal vein is tolerated in cows and whether the glucose concentration differs after administration of glucose into the jugular vein and portal vein. Fifteen healthy Swiss Braunvieh cows were used. An indwelling catheter was placed in both jugular veins and a balloon-tipped indwelling catheter with a diameter of 2 mm was placed in the portal vein under the guidance of ultrasonography. Three cows received 500 ml of 20% glucose solution over 60 min via the left jugular vein. Three other cows received the same solution over 60 min via the portal vein. Blood samples were collected from the right jugular vein before and for 24 h after the infusion of glucose for the determination of the concentrations of glucose and bilirubin and the activities of glutamate dehydrogenase, sorbitol dehydrogenase and gamma-glutamyl transferase. Infusion via the portal vein did not result in abnormalities in the general condition of the cows or increases in the concentration of bilirubin or the activities of liver enzymes. The blood glucose concentration increased to the same extent after both intraportal and intrajugular infusion. Over a 12-h period, three cows received 10 l of 20% glucose solution via the left jugular vein and three others received the same solution over a 12-h period via the portal vein. Blood samples were collected from the right jugular vein before and for 30 h after the start of infusion. Infusion via the portal vein did not affect the general condition of the cows or the activities of the liver enzymes. There was no significant difference in the blood glucose concentration between the two groups throughout the study.
...
PMID:Comparison of blood glucose concentrations after administration of a glucose solution via the jugular vein and portal vein in cows. 1787 78

Significant disorders of liver metabolic pathways enzymes after high-cholesterol diet could give information on liver steatosis development. This process could probably also be inhibited by some compounds, as examined in rabbits. Forty-two male rabbits were served a high-cholesterol diet (2 g%) (0.67 g/kg b.m./24 h) with addition of d,l-methionine (70 mg/kg b.m./24 h) or seleno-d,l-methionine (12.5 microg/kg b.m./24 h) or alpha-tocopherol (10 mg/kg b.m./24 h) for 3 months to compare the protection effect of used compounds on liver metabolism and steatosis. At the beginning and every month, blood was taken. After the experiment was completed, livers were dissected for histological examinations. The concentration of total cholesterol (t-CH), triacylglycerol (TG), and the activities of aldolase (ALD), sorbitol dehydrogenase (SDH), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were determined. Plasma t-CH and TG concentrations were significantly higher in all experimental groups vs control group. Blood serum AST and ALT activities did not undergo change but there were observed not significant increase in the CH group vs control group. Activities of SDH, GLDH, and LDH increased in blood serum and decreased in the liver in all experimental groups. Activities of LDH and SDH increased in the liver in the CH+Met group vs CH group. ALD activity decreased in the liver only in the CH and CH+Se groups. This data support a lipotoxic model of cholesterol-mediated hepatic steatosis. Prolonged administration of high-cholesterol diet not only disturbs the structure of cell membranes, which is expressed by decreased activity of enzymes in the liver and the migration of those enzymes to plasma but as well leads to steatosis of the liver, which has been confirmed by histological examinations. The applied compounds appear to have a varying influence upon the activity of enzymes determined in serum and liver. Obtained results showed a beneficial influence of methionine and vitamin E supplementation on liver steatosis development.
...
PMID:The influence of methionine, selenomethionine, and vitamin E on liver metabolic pathways and steatosis in high-cholesterol fed rabbits. 1791 70

The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTalpha) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in early clinical trials.
...
PMID:The current state of serum biomarkers of hepatotoxicity. 1829 70


<< Previous 1 2 3 4 5 6 7 Next >>

---