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)

Microsome, cytosol and serum malathion carboxylesterase (MaCEst) activity was assessed in rats after single i.p. administration of carbon tetrachloride (CCl4) in doses ranging from 0.05 to 1 ml kg-1. MaCEst activities were compared with those of glucose-6-phosphatase (G6-Pase) as an indicator of endoplasmic reticulum damage and serum glutamate dehydrogenase (GLDH) and sorbitol dehydrogenase (SHD) as indicators of liver cytolysis. The data showed a dose-dependent increase in GLDH and SDH serum activities (175% and 68%) from 0.05 ml kg-1; an increase in serum G6-Pase (31%) and a decrease in microsomal G6-Pase (38%) was apparent only after 0.5 or 1.0 ml kg-1 doses. MaCEst activity was unaffected. The results demonstrate that, under these experimental conditions, serum and subcellular measurements of MaCEst activity failed to reveal the liver toxicity of CCl4.
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PMID:Difference in liver and serum malathion carboxylesterase and glucose-6-phosphatase in detecting carbon tetrachloride-induced liver damage in rats. 166 44

Selected serum parameters (enzyme activities and triglycerides) and liver glutathione and vitamin C concentrations were measured in English sole (Parophrys vetulus) after i.p. injection of carbon tetrachloride (CCl4), a hepatotoxin in fish. Serum lactate dehydrogenase (LDH), alkaline phosphatase (AP) and glutamate dehydrogenase (GDH) activities and the concentration of triglycerides increased in a dose-dependent manner 24 hr post injection. Concentrations of glutathione (reduced and oxidized) and ascorbic acid (vitamin C) in liver did not change in response to CCl4 toxicity 24 hr post injection. These studies indicate that serum AP activity and triglyceride concentrations can be useful in assessing the effects of CCl4-induced liver toxicity in this species of marine fish. Serum LDH and GDH activity should be used with some caution in assessing liver damage in English sole, as other tissues represent more likely sources for serum activity. The levels of liver antioxidants do not appear to be significantly affected, 24 hr post injection, by this particular hepatotoxin.
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PMID:Hepatotoxic effects of CCl4 on English sole (Parophrys vetulus): possible indicators of liver dysfunction. 287 55

The ability of 14 serum biochemical assays to predict the presence of hepatic necrosis induced by carbon tetrachloride (CCl4) (centrilobular necrosis), allyl alcohol (periportal necrosis), and 1-napththylisothiocyanate (ANIT) (biliary duct necrosis) was evaluated in rats. Results of these assays were analyzed using multivariate discriminant analysis to determine: which assays have the highest predictive value for discriminating between control and treated rats, and which assays would discriminate between rats in the three treatment groups. Individual assays with the highest predictive value for CCl4-induced lesions versus controls were glutamate dehydrogenase (GDH), sorbitol dehydrogenase (SDH), and alanine aminotransferase (ALT). Assays with the highest predictive value for ANIT-induced lesions were GDH, 5'-nucleotidase (5'NT), and ALT. Assays the highest predictive value for ANIT-induced lesions were GDH, 5'-nucleotidase (5'NT), and ALT. Assays with the highest predictive value for allyl alcohol-induced lesions were an ALT/isocitrate dehydrogenase (ICD) ratio, GDH, and ALT. Canonical correlation coefficients for each assay ranged from 0.98 to 0.91 with 95-100% correct group membership predictions (treated versus control) provided by each assay. Individual assays were not highly predictive for determining group membership among all three treatment groups. A two assay combination of 5'NT and an ALT/ICD ratio provided 100% correct group membership predictions and had high canonical correlations (f1 = 0.95, f2 = 0.83).
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PMID:Evaluating toxin-induced hepatic injury in rats by laboratory results and discriminant analysis. 301 5

CCl4 is proposed to induce cellular injury through its metabolites that are generated by a cytochrome P-450 dependent step. These free radical products can interact with membrane structures, thereby generating lipid peroxides. The latter process has been implicated as a major mechanism of CCl4 hepatoxicity, although this relationship has been difficult to demonstrate when using isolated hepatocyte preparations. This report demonstrates that there are at least two mechanisms by which CCl4 induces injury in isolated hepatocytes. One occurs within minutes of exposure to CCl4 and is characterized by modest malondialdehyde formation and no decline in cellular-reduced glutathione. SKF 525A, metyrapone and promethazine did not protect against this early damage. A second phase of damage, evident particularly after 3 hr, is characterized by a marked increase in malondialdehyde formation, a fall in cellular glutathione and substantial further cellular damage. These changes could be moderated by the cytochrome P-450 inhibitors and promethazine, and antioxidant. Further examination of the initial phase of damage reveals an immediate dose-related inhibition of O2 consumption. This could not be prevented by SKF 525A or metyrapone and was associated with loss of ability to stimulate mitochondrial respiration with dinitrophenol. Rapid recovery to initial O2 consumption rates occurred with time as CCl4 evaporated from the incubation system. This was associated with a partial return of dinitrophenol stimulation of mitochondrial O2 consumption despite significant glutamate dehydrogenase release. A portion of this recovery could be inhibited by SKF 525A, suggesting that some O2 consumption was due to CCl4 metabolism and ensuing lipid peroxidation. These data suggest that early CCl4 toxicity is a direct consequence of its solvent properties and is partially reversible; subsequent damage may be mediated by lipid peroxidation. This solvent injury has not been previously recognized and may have relevance not only to a reversible toxicity as demonstrated with isolated hepatocytes but also in vivo as well.
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PMID:CCl4-induced toxicity in isolated hepatocytes: the importance of direct solvent injury. 394 88

To study the effect of an acute dose of ethanol on carbon tetrachloride (CCl4) concentration and hepatotoxicity, female rats received ethanol (2.5 ml/kg body wt.) either intragastrically or intraperitoneally following intragastric administration of CCl4 (1.5 ml/kg body wt.). Three hours after acute CCl4 intoxication there was a striking increase in CCl4 concentration in animals treated simultaneously with ethanol intragastrically compared to those receiving ethanol intraperitoneally. This increase was significant (P less than 0.05) and amounted to 211% for blood, 236% for liver and 405% for fat tissue, whereas animals treated with CCl4 alone showed CCl4 concentrations in the range between the two other experimental groups. Serum activities of glutamate oxalacetate transaminase, glutamate pyruvate transaminase and glutamate dehydrogenase were found to be considerably higher in animals treated with the combination of CCl4 and ethanol when compared to those receiving CCl4 alone, showing that ethanol given intraperitoneally or intragastrically enhances CCl4 hepatotoxicity. Since the intraperitoneal administration of ethanol led to a reduction rather than an increase in CCl4 concentration in the early phase of intoxication, additional mechanisms independent of actual levels of CCl4, such as direct effects of ethanol on the CCl4 metabolizing enzyme of the membrane of the endoplasmic reticulum, have to be implicated in the pathogenesis of the potentiation of CCl4 hepatotoxicity by ethanol.
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PMID:Effect of ethanol on carbon tetrachloride levels and hepatotoxicity after acute carbon tetrachloride poisoning. 653 81

Peak levels of carbon tetrachloride (CCl4) as determined by head-space gas chromatography were observed 3-6 h following an acute oral dose of CCl4 in the blood, liver and fat of rats. Subsequently, there was a rapid decline of CCl4 levels. Conversely, serum activities of enzymes originating from the liver such as glutamate oxalacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and glutamate dehydrogenase (GDH) increased considerably and showed activity peaks between 12-48 h following CCl4 administration, indicating a delayed response of CCl4 on the activity levels of enzymes in the blood.
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PMID:Carbon tetrachloride (CCl4) levels and serum activities of liver enzymes following acute CCl4 intoxication. 662 3

The effect of carrot extract on carbon tetrachloride (CCl4)-induced acute liver damage was evaluated. The increased serum enzyme levels (viz., glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, lactate dehydrogenase, alkaline phosphatase, sorbitol and glutamate dehydrogenase) by CCl4-induction were significantly lowered due to pretreatment with the extract. The extract also decreased the elevated serum bilirubin and urea content due to CCl4 administration. Increased activities of hepatic 5'-nucleotidase, acid phosphatase, acid ribonuclease and decreased levels of succinic dehydrogenase, glucose-6-phosphatase and cytochrome P-450 produced by CCl4 were reversed by the extract in a dose-responsive way. Results of this study revealed that carrot could afford a significant protective action in the alleviation of CCl4-induced hepatocellular injury.
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PMID:Hepatoprotective activity of carrot (Daucus carota L.) against carbon tetrachloride intoxication in mouse liver. 750 Jun 38

The main pathway for the hepatic oxidation of ethanol to acetaldehyde proceeds via ADH and is associated with the reduction of NAD to NADH; the latter produces a striking redox change with various associated metabolic disorders. NADH also inhibits xanthine dehydrogenase activity, resulting in a shift of purine oxidation to xanthine oxidase, thereby promoting the generation of oxygen-free radical species. NADH also supports microsomal oxidations, including that of ethanol, in part via transhydrogenation to NADPH. In addition to the classic alcohol dehydrogenase pathway, ethanol can also be reduced by an accessory but inducible microsomal ethanoloxidizing system. This induction is associated with proliferation of the endoplasmic reticulum, both in experimental animals and in humans, and is accompanied by increased oxidation of NADPH with resulting H2O2 generation. There is also a concomitant 4- to 10-fold induction of cytochrome P4502E1 (2E1) both in rats and in humans, with hepatic perivenular preponderance. This 2E1 induction contributes to the well-known lipid peroxidation associated with alcoholic liver injury, as demonstrated by increased rates of superoxide radical production and lipid peroxidation correlating with the amount of 2E1 in liver microsomal preparations and the inhibition of lipid peroxidation in liver microsomes by antibodies against 2E1 in control and ethanol-fed rats. Indeed, 2E1 is rather "leaky" and its operation results in a significant release of free radicals. In addition, induction of this microsomal system results in enhanced acetaldehyde production, which in turn impairs defense systems against oxidative stress. For instance, it decreases GSH by various mechanisms, including binding to cysteine or by provoking its leakage out of the mitochondria and of the cell. Hepatic GSH depletion after chronic alcohol consumption was shown both in experimental animals and in humans. Alcohol-induced increased GSH turnover was demonstrated indirectly by a rise in alpha-amino-n-butyric acid in rats and baboons and in volunteers given alcohol. The ultimate precursor of cysteine (one of the three amino acids of GSH) is methionine. Methionine, however, must be first activated to S-adenosylmethionine by an enzyme which is depressed by alcoholic liver disease. This block can be bypassed by SAMe administration which restores hepatic SAMe levels and attenuates parameters of ethanol-induced liver injury significantly such as the increase in circulating transaminases, mitochondrial lesions, and leakage of mitochondrial enzymes (e.g., glutamic dehydrogenase) into the bloodstream. SAMe also contributes to the methylation of phosphatidylethanolamine to phosphatidylcholine. The methyltransferase involved is strikingly depressed by alcohol consumption, but this can be corrected, and hepatic phosphatidylcholine levels restored, by the administration of a mixture of polyunsaturated phospholipids (polyenylphosphatidylcholine). In addition, PPC provided total protection against alcohol-induced septal fibrosis and cirrhosis in the baboon and it abolished an associated twofold rise in hepatic F2-isoprostanes, a product of lipid peroxidation. A similar effect was observed in rats given CCl4. Thus, PPC prevented CCl4- and alcohol-induced lipid peroxidation in rats and baboons, respectively, while it attenuated the associated liver injury. Similar studies are ongoing in humans.
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PMID:Role of oxidative stress and antioxidant therapy in alcoholic and nonalcoholic liver diseases. 889 26

CCl4-induced cirrhosis of rats was used for studying the influence of L-ornithine-L-aspartate (OA) on hyperammonemia. OA given to cirrhotic rats (2 g/kg daily) for 2 wk slightly increased net body weight and led to a significant increase in plasma urea levels and a decrease in plasma ammonia levels. Serum concentrations of glutamate, glutamine and arginine decreased significantly. In the livers of the OA-treated rats the activities of carbamoylphosphate synthetase I and arginase increased by 30 and 40%, respectively, approaching normal levels. No change in the activities of the other urea cycle enzymes as well as of glutamate dehydrogenase, glutaminase and glutamine synthetase was found. The negative correlation between glutamine synthetase activity and plasma ammonia levels reported previously for cirrhotic rats (Gebhardt and Reichen, Hepatology 20:684-691, 1994) was corroborated for cirrhotic animals not treated with OA, but was no longer apparent in OA-treated cirrhotic rats. Despite this improvement, plasma ammonia levels still varied considerably reflecting the variable accessibility and activities of glutamine synthetase in cirrhotics. Cultured hepatocytes from the two groups of rats showed a similar stimulation of urea production by addition of ammoniumacetate and/or OA to Hanks' buffered salt solution. In Williams medium E, however, the hepatocytes from the OA group produced significantly more urea than those from controls. These results suggest that treatment of cirrhotic rats with OA considerably improves urea production favoring the detoxification of ammonia that, however, is still limited by the severe alterations in liver architecture that are not influenced by OA in a 2-wk period.
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PMID:Treatment of cirrhotic rats with L-ornithine-L-aspartate enhances urea synthesis and lowers serum ammonia levels. 933 1

In experiments on 182 white male rats hepatitis was modelled by percutaneous injection of 0.1 ml/500 g of tetrachloromethane (TCM) dissolved in olive oil. TCM was injected every other day for 65 days. After development of hepatitis (in 65 days) synthesis of glutamine and urea, partial oxygen pressure in the liver were studied. It is shown that modelling of chronic hepatitis leads to impairment of glutamine and urea synthesis, reduction of tissue blood flow and oxygen partial pressure. It is suggested that the reason of these changes is inhibition activity of glutamate dehydrogenase, arginase and short-term depression activity of phosphate-dependent glutaminase. The changes in the enzymatic activity lead to lowering tissue level of glutamine, urea, accumulation of ammonia ions. These changes persist for 14 days after the last injection of tetrachloromethane.
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PMID:[The ammonia neutralization function of the liver in chronic active hepatitis]. 1505 75


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