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

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper reports a study of changes in red blood cell enzymes and some serum parameters during and after treatment of protein-calorie malnutrition. The red cell GSH levels were low during the crisis, together with the levels of GSSG:NADPH reductase, GSH:H2O2 peroxidase, aspartate aminotransferase and alanine aminotransferase. After treatment the levels of all these enzymes increased significantly to normal values. Of the serum parameters investigated, significant reduction in the activity of the enzymes cholinesterase, catecholamine oxidase, total proteins, albumin, urea and electrolytes were obvious, and returned to normal values after treatment. Ceruloplasmin activity remained low even after three weeks' treatment and could not be related to copper levels. The results are discussed in relation to anemia and liver damage that may accompany the syndrome.
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PMID:Protein-calorie malnutrition: a study of red blood cell and serum enzymes during and after crisis. 82 Apr 94

This study was designed to clarify the effects of changes in liver tissue glutathione (GSH) concentration on postischemic liver injury together with the effects of gamma-glutamylcysteine ethyl ester (GCE), a prodrug of GSH, and GSH. Rats were pretreated with GSH (50 mg/kg, i.v.), or GCE (50 mg/kg, i.v.), or untreated. In each rat, liver was isolated, and liver mitochondria were prepared after 2 h of ischemia or 1 h of reperfusion following 2 h of ischemia. Mitochondrial function was measured polarographically. Liver adenine nucleotide concentrations were also determined using high-performance liquid chromatography. Liver tissue GSH, an oxidized form of glutathione (GSSG) concentrations, and activities of GSH peroxidase and GSSG reductase were determined enzymatically. Liver hypoxanthine and xanthine concentrations were determined by HPLC. Liver tissue concentration of lipid peroxide was measured. Leakages of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and adenine nucleotides into the hepatic vein after reperfusion were also measured. Administration of GCE improved the recovery of mitochondrial function and maintained tissue GSH concentration concomitantly. Increases in liver lipid peroxide concentration after reperfusion, and leakage of liver cell enzymes and adenine nucleotides were mitigated by administration of GCE. Administration of GSH itself failed to maintain tissue GSH concentration and had no protective effects. From these results, it is concluded that in the postischemic process, free radical formation might be enhanced, and the radical scavenging system deteriorated. To enhance the radical scavenging system is a possible maneuver to prevent radical-related cell damage associated with reperfusion, because pharmacological reduction of breakdown of ATP to hypoxanthine and xanthine seems to be difficult. GCE maintained liver GSH concentrations and mitigated postischemic liver injury, concomitantly. Clinical use of GCE might be recommended.
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PMID:The effects of gamma-glutamylcysteine ethyl ester, a prodrug of glutathione, on ischemia-reperfusion-induced liver injury in rats. 833 63

To investigate the role of neutrophils (PMNs) and PMN-dependent adhesion molecules in the pathogenesis of liver injury in a model of endotoxin shock, male ICR mice received a dose of 700 mg/kg galactosamine and 100 micrograms/kg Salmonella abortus equi endotoxin. PMNs accumulated continuously in the liver, reaching values of 446 +/- 71 PMNs/50 high-power fields at 9 h (basal value 18 +/- 7). Plasma alanine aminotransferase activities as index of parenchymal cell injury did not change up to 5 h posttreatment (basal value 35 +/- 5 U/l) but increased to 1,950 +/- 460 U/l at 9 h. The formation of glutathione disulfide (GSSG) in plasma as an index of an extracellular oxidant stress also increased only at 9 h. Pretreatment of animals with monoclonal antibodies against the CD11b and CD18 subunits of the CD11/CD18 integrin family on the surface of the PMN reduced the number of PMNs in the liver by 50% and significantly attenuated liver injury and GSSG formation. An anti-CD11a and a nonbinding control antibody were ineffective. It is concluded that PMNs are actively involved in the pathogenesis of galactosamine and endotoxin shock and that at least in part the accumulation of PMNs, the subsequent oxidant stress, and the tissue injury in this model of experimental hepatitis are CD11b/CD18 (Mac-1) dependent.
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PMID:Neutrophil-induced liver cell injury in endotoxin shock is a CD11b/CD18-dependent mechanism. 176 46

The effect of bucillamine (BA) on glutathione (GSH) and GSH-related enzymes was investigated in C57 mouse. Administration of high doses of BA (150-400 mg/kg) produced a dose-dependent depletion (20-44%) of hepatic GSH, which was similar in magnitude to that produced by equimolar doses of other sulphydryl drugs studied previously. GSH depletion after acute BA administration correlated well with the elevation of serum glutamic-pyruvic transaminase (SGPT) (6-9-fold increase above control). The increase in SGPT after chronic administration (7 days), although significantly higher than the controls, was however much less than after acute administration. The hepatic GSH concentrations of mice given 7 days of BA were similar to the controls, again correlating well with SGPT activity. Administration of BA (150-400 mg/kg) caused also a significant dose-dependent increase in the oxidized glutathione (GSSG) in blood by 2-7-fold, as well as a dose-dependent increase in blood glutathione S-transferase (GST) activity (2-13-fold). In an in vitro experiment, hepatic GST activity was activated by various concentrations of BA (1 microM-1mM). There was little or no effect on GSSG reductase and on glutathione peroxidase (GSH-Px) after acute administration of BA. Chronic administration of BA had no effect on hepatic GSSG reductase and GSH-Px, but GSSG reductase activity in blood was increased significantly by 4-fold. It is possible that BA may affect the redox status through auto-oxidation and oxidation with endogenous thiols such as glutathione, affecting GSH concentrations and the GSH/GSSG ratio in tissues and, thus, having both metabolic and toxicological consequences. Whether or not the induction of GST activity in vivo in blood and in vitro in liver enzyme preparations shared the same underlying mechanism(s) requires further investigation.
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PMID:The effects of bucillamine on glutathione and glutathione-related enzymes in the mouse. 186 40

Lipid peroxidation (LPO) and alterations in cellular systems protecting against oxidative damage were determined in the liver, kidney and skeletal muscle of male F344/NCr rats, 1 h to 3 days after a single intraperitoneal (i.p.) injection of 107 mumol nickel(II)acetate per kg body weight. At 3 h, when tissue nickel concentrations were highest, the following significant (at least, P less than 0.05) effects were observed: in kidney, increased LPO (by 43%), increased renal iron (by 24%), decreased catalase (CAT) and glutathione peroxidase (GSH-Px) activities (both by 15%), decreased glutathione (GSH) concentration (by 20%), decreased glutathione reductase (GSSG-R) activity (by 10%), and increased glutathione-S-transferase (GST) activity (by 44%); the activity of superoxide dismutase (SOD) and gamma-glutamyl transferase (GGT), as well as copper concentration, were not affected. In the liver, nickel effects included increased LPO (by 30%), decreased CAT and GSH-Px activities (both by 15%), decreased GSH level (by 33%), decreased GSSG-R activity (by 10%) and decreased GST activity (by 35%); SOD, GGT, copper, and iron remained unchanged. In muscle, nickel treatment decreased copper content (by 43%) and the SOD activity (by 30%) with no effects on other parameters. In blood, nickel had no effect on CAT and GSH-Px, but increased the activities of alanine-(ALT) and aspartate-(AST) transaminases to 330% and 240% of the background level, respectively. In conclusion, nickel treatment caused profound cell damage as indicated by increased LPO in liver and kidney and leakage of intracellular enzymes, ALT and AST to the blood. The time pattern of the resulting renal and hepatic LPO indicated a possible contribution to its magnitude from an increased concentration of nickel and concurrent inhibition of CAT, GSH-Px and GSSG-R, but not from increased iron or copper levels. The oxidative damage expressed as LPO was highest in the kidney and lowest in the muscle, which concurs with the corresponding ranking of nickel uptake by these tissues.
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PMID:Nickel induced lipid peroxidation in the rat: correlation with nickel effect on antioxidant defense systems. 197 9

The objective of this study was to test the hypothesis that the extracellular oxidation of glutathione (GSH) may represent an important mechanism to limit hepatic ischemia/reperfusion injury in male Fischer rats in vivo. Basal plasma levels of glutathione disulfide (GSSG: 1.5 +/- 0.2 microM GSH-equivalents), glutathione (GSH: 6.2 +/- 0.4 microM) and alanine aminotransferase activities (ALT: 12 +/- 2 U/l) were significantly increased during the 1 h reperfusion period following 1 h of partial hepatic no-flow ischemia (GSSG: 19.7 +/- 2.2 microM; GSH 36.9 +/- 7.4 microM; ALT: 2260 +/- 355 U/l). Pretreatment with 1,3-bis-(2-chloroethyl)-1-nitrosourea (40 mg BCNU/kg), which inhibited glutathione reductase activity in the liver by 60%, did not affect any of these parameters. Biliary GSSG and GSH efflux rates were reduced and the GSSG-to-GSH ratio was not altered in controls and BCNU-treated rats at any time during ischemia and reperfusion. A 90% depletion of the hepatic glutathione content by phorone treatment (300 mg/kg) reduced the increase of plasma GSSG levels by 54%, totally suppressed the rise of plasma GSH concentrations and increased plasma ALT to 4290 +/- 755 U/l during reperfusion. The data suggest that hepatic glutathione serves to limit ischemia/reperfusion injury as a source of extracellular glutathione, not as a cofactor for the intracellular enzymatic detoxification of reactive oxygen species.
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PMID:Vascular oxidant stress and hepatic ischemia/reperfusion injury. 206 Aug 45

In isolated, hemoglobin-free perfused livers of fasted rats, formaldehyde at an initial concentration of 10 mmol/l produced toxicity as evidenced by a release of enzymes (GPT, SDH) and of glutathione (mainly GSSG) into the perfusate, an accumulation of calcium in the liver, and a depletion of hepatic glutathione. Formaldehyde also led to an enhanced release of malondialdehyde into the perfusate, indicating peroxidative processes and decreased hepatic oxygen consumption by about 50-70%. The electron microscopic investigation of formaldehyde-exposed livers showed a destruction of the mitochondria (ruptured membranes, loss of the cristae) and some damage of the rough endoplasmic reticulum. Feeding the rats prior to surgery attenuated the hepatotoxic effects of 10 mmol/l formaldehyde. At an initial concentration of 3 mmol/l, formaldehyde did not release enzymes from livers of fed or fasted rats but only from those whose glutathione content had been depleted by treatment with phorone (250 mg/kg ip 2 h earlier). Formaldehyde liberated glucose and lactate from the livers of fed but not from those of fasted rats, indicating anaerobic energy supply in the fed state. The hepatotoxic action of formaldehyde is not due to its metabolism to formate or to the 10% methanol added as a stabilizing agent to the commercially available 37% solution named formalin. In conclusion, by destruction of mitochondria, formaldehyde inhibits aerobic energy supply and thereby presumably produces hepatocellular damage.
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PMID:Mechanistic study on formaldehyde-induced hepatotoxicity. 275 59

Male Wistar rats received methyl methacrylate monomer (MMA) i.p. in olive oil 1.0 g/kg body weight on 3 successive days. The weight of the livers and kidneys, and the body weights did not differ from their controls. On the fifth day after treatment, hepatic NADPH-cytochrome c reductase, 7-ethoxycoumarin 0-deethylase and the 2,5-diphenyloxazole hydroxylase exhibited maximal decreases in activity (25%, 58%, 36%, respectively) without any coincident effect on the total amount of cytochrome P-450 hemoprotein itself. One week later these activities had returned to control levels. The enzymatic changes in the kidneys were smaller in magnitude, and they were also reversed sooner. A single i.p. dose of MMA (2 g/kg body weight) caused elevation of serum alanine aminotransferase activity. A tenfold increase of the excretion rate of urinary thioethers was also discovered. The hepatic reduced glutathione (GSH) was depleted in 3 h to 20% and the GSSG to half of the value in controls. In kidneys, the GSH was decreased to 48% in 3 h before an apparent phase of overrecovery. At the end of the 24 h observation period, cytochrome P-450 concentrations were somewhat decreased in the liver. The GSH contents showed dose and time-dependent reversible decreases in isolated hepatocytes when incubated for 2 h in a medium containing MMA at the nominal concentrations of 0, 2, 5, or 10 mM. None of the treatments affected either the content of cytochrome P-450 or the viability of the liver cells.
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PMID:Effects of methyl methacrylate on non-protein thiols and drug metabolizing enzymes in rat liver and kidneys. 640 23

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

We investigated whether intraportal injection of 150 mg/kg N-acetylcysteine (NAC) into rats reduced hepatic ischemia-reperfusion injury after 48 hours of cold storage and 2 hours of reperfusion. The organ was isolated and perfused to evaluate liver function. The control group received an intraportal injection of 5% dextrose. NAC increased L-cysteine concentrations 15 minutes after injection (1.29 +/- 0.11 mumol/g vs. 2.68 +/- 0.4 mumol/g, P < .05). However, neither treatment modified glutathione liver concentrations relative to preinjection values. After 48 hours of cold storage and 2 hours of reperfusion, livers from NAC-treated rats produced larger amounts of bile than those in the control group (5.04 +/- 1.92 vs. 0.72 +/- 0.37 microL/g liver; P < .05), and showed a significant reduction in liver injury, as indicated by reduced release of lactate dehydrogenase (679.4 +/- 174.4 vs. 1891.3 +/- 268.3 IU/L/g; P < .01), aspartate transaminase (AST) (13.94 +/- 3.5 vs. 38.75 IU/L/g; P < .01), alanine transaminase ALT) (14.92 +/- 4.09 vs. 45.91 +/- 10.58 IU/L/g; P < .05), and acid phosphatase, a marker of Kupffer cell injury (344.4 +/- 89.6 vs. 927.3 +/- 150.8 IU/L/g; P < .01) in the perfusate. Reduced glutathione concentrations in the perfusate were similar in the two groups (805 +/- 69 vs. 798 +/- 252 nmol/L/g), whereas oxidized glutathione (GSSG) concentrations were higher in the control group (967 +/- 137 vs. 525 +/- 126 nmol/L/g; P < .05). Reduced glutathione (GSH) concentrations in liver tissue collected at the end of perfusion were significantly higher in the NAC group (7.3 +/- 0.9 vs. 4.1 +/- 1.0 mumol/g; P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effects of N-acetylcysteine on hypothermic ischemia-reperfusion injury of rat liver. 763 22


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