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)

The ability of morphine and other opioid analgesic drugs to diminish hepatocellular glutathione (GSH) concentrations was examined in ICR mice. When administered intraperitoneally, morphine, hydromorphone, ethylmorphine, l-alpha-acetylmethadol (LAAM), and meperidine all caused a significant decrease in hepatic GSH concentrations in male mice while codeine, methadone, butorphanol, nalbuphine, and pentazocine were without effect even at doses up to those approaching acute lethality. Depression of hepatic GSH equivalent to that observed after ip administration could be elicited by icv administration of small doses of morphine, ethylmorphine, and hydromorphone. LAAM and meperidine were ineffective following icv administration in these experiments. The discrepancy between results following ip versus icv administration of LAAM and meperidine suggests that hepatic metabolism of some opioids may be important for their activity in the CNS, as both norLAAM and normeperidine diminished hepatic GSH when administered by the icv route. The opioid-induced lowering of hepatic GSH does not appear to be sex-dependent since morphine and LAAM produced qualitatively and quantitatively similar effects on hepatic GSH in female mice. Morphine administered icv produced a substantial increase in the hepatotoxicity of two compounds dependent upon GSH for detoxification, acetaminophen and cocaine, as measured by serum alanine aminotransferase activities. These observations indicate that a number of opioid analgesic drugs have the potential to diminish hepatic GSH. Further, these results support earlier studies which indicate that central opioid effects on hepatic GSH are mediated through mu-opioid receptor stimulation. Last, these studies suggest that a centrally initiated opioid action on hepatic GSH may significantly influence the susceptibility of the liver to the effects of some hepatotoxic agents.
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PMID:Depression of hepatic glutathione by opioid analgesic drugs in mice. 247 Dec 91

Acetaminophen (AA) was administered i.p. to Swiss mice as a single dose 100, 200, 300, 400 and 600 mg/kg. At different time periods after administration, the mice were sacrificed. Serum glutamate-pyruvate transaminase (SGPT) and sorbitol dehydrogenase (SDH) as well as glutathione (GSH) levels in the liver were determined. It was found that the effective dose ranged within 200-600 mg/kg. Changes in GSH level occurred shortly after acetaminophen administration, whereas changes in the activity of indicatory enzymes were slightly delayed compared to this process. Conditions allowing for parallel observations of all three indices under investigation occurred 4 hrs after acetaminophen administration. With regard to glutathione, directly measured decrease, as compared to control levels, may be used as the yardstick of the changes. Changes in the activity of indicatory enzymes may be better expressed in the dose-response arrangement. For all the indices determined 4 hrs after acetaminophen administration, ED50 is in the range 200-300 mg/kg.
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PMID:Dynamics of glutathione levels in liver and indicatory enzymes in serum in acetaminophen intoxication in mice. 248 10

For the purpose of clarifying the cause of white muscle disease (WMD) in calves, tocopherol and selenium levels and blood glutathione peroxidase (GSH-Px) activity were measured on 10 calves with WMD and nine of their dams. The main clinical symptoms of the 10 calves with WMD were motor disturbances including recumbency and stiffness. Serum enzyme activities (GOT, GPT, CPK, LDH) in calves with WMD increased markedly, and this increase was also observed in some of their dams. Serum tocopherol levels of calves with WMD were low, 70% of which showing deficient levels of less than 70 micrograms/100 ml. Serum selenium levels of all the calves were lower than 35 ppb, indicating a deficiency, and were accompanied by low blood GSH-Px activity. alpha-Tocopherol and selenium concentrations in organs were very low. Dams of calves with WMD showed low serum tocopherol levels, 22% of which indicating deficient levels below 150 micrograms/100 ml. Serum selenium levels in dams showed a marked decrease to under 20 ppb, and also low blood GSH-Px activity. Feedstuffs supplied in the farms to affected calves indicated very low alpha-tocopherol contents (below 3 mg/100g DM) and low selenium concentrations below 50 ppb in DM. It was concluded that WMD in calves was attributable to nutritional muscular dystrophy caused by deficiencies in tocopherol and selenium in feedstuffs supplied to their dams.
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PMID:Studies on serum tocopherol, selenium levels and blood glutathione peroxidase activities in calves with white muscle disease. 258 29

The activity of several blood enzymes in the presence and absence of arsenite (As) and cadmium (Cd) was investigated under in vitro conditions. Both human and rat blood glutathione peroxidase (GSH-Px) activities were adversely affected by As at the 0.8 and 1.6 micrograms/ml levels. The latter was completely inactivated whereas the former retained approximately 30% of its original activity. The effect of Cd on this enzyme was much smaller: 650 g Cd/ml were needed to decrease its activity by 30% of the original value. As noted for GSH-Px, the rat's glutamyl oxaloacetate transaminase (GOT) appears to be appreciably more sensitive to the As inhibitory effect than the human enzyme (by a factor of 3). Cd, however, failed to bring about any inhibition of GOT. In the case of glutamyl pyruvate transaminase (GPT) both As and Cd had a marked effect, manifested in 70% and 78% inhibition, respectively. Blood glucose-6-phosphate dehydrogenase (G-G-PD) was inhibited by both Cd and As, however, within the concentration range used, only Cd inhibited it completely. Cholinesterase (ChE) activity was inhibited completely by both Cd and As.
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PMID:In vitro effects of cadmium and arsenite on glutathione peroxidase, aspartate and alanine aminotransferases, cholinesterase and glucose-6-phosphate dehydrogenase activities in blood. 261 33

Humans risk inadvertent intraperitoneal or intravenous exposure to formaldehyde (HCHO), commonly used for disinfection of implanted or extracorporeal medical devices. Various chemical and physical stresses are known to induce hepatic metallothionein. This study examined the effect of acute parenteral administration of HCHO on induction of hepatic metallothionein synthesis. Adult male CF1 mice were administered HCHO ip and hepatic metallothionein was quantified by the cadmium-radioassay method. HCHO (50 mg/kg) increased hepatic metallothionein as early as 8 hr after dosing with maximal levels (27-fold increase) occurring at 72 hr. Metallothionein concentrations were elevated (15-fold) 24 hr after 50 or 100 mg HCHO/kg but not at lower dosages. Concomitant elevations in hepatic zinc and copper content were observed. No increases in metallothionein were observed in kidney, pancreas, or intestine 24 hr after HCHO administration (100 mg/kg, ip). Induction of metallothionein by HCHO may reflect direct de novo synthesis since the response was abolished by pretreatment with the RNA synthesis inhibitor, actinomycin D. HCHO induction of metallothionein also does not appear to be mediated by stress-induced release of corticosteroids or catecholamines from the adrenal since the response was unaltered in adrenalectomized mice. Interference with the glutathione (GSH)-dependent oxidation of HCHO by reducing hepatic GSH concentrations to 40% of control after a 2-hr pretreatment with phorone decreased the metallothionein induction response to HCHO by 33%. This result suggests that the induction may be partially due to a HCHO metabolite, e.g., formate. Confirmation of metallothionein synthesis was obtained following spectral and chromatographic analysis. Thus, HCHO and/or a metabolite produces a marked increase in hepatic metallothionein and alters hepatic zinc and copper homeostasis, all of which are transient responses. Although HCHO was only mildly hepatotoxic at the highest dose (as evidenced by an increase in plasma alanine aminotransferase activity), such changes in metallothionein synthesis and essential metal homeostasis may be part of a cellular repair mechanism operant after acute toxic cell injury.
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PMID:Acute exposure to formaldehyde induces hepatic metallothionein synthesis in mice. 271 95

The relationship between carbon tetrachloride (CCl4)-induced hepatotoxicity and hepatic glutathione (GSH) content was investigated in fed and fasted rats. The elevation of serum glutamic-pyruvic transaminase (GTP) activity by CCl4 treatment was enhanced by fasting. Although the hepatic GSH content fo 12-hour-fasted rats was higher than that of fed rats determined at 6 p.m., the serum GPT activity of the former was higher than that of the latter. Starvation had no effect on the activities of hepatic glutathione peroxidase (GSH-Px) and glutathione reductase (GR). The results suggest that the potentiation of hepatic injury by CCl4 cannot be related to hepatic GSH content.
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PMID:Relationship between hepatic glutathione content and carbon tetrachloride-induced hepatotoxicity in vivo. 271 15

The objective of this study was to determine the effect of prolonged ingestion of acetaminophen (ACAP) on the availability of methionine for its metabolic functions in mice. ACAP was fed to weanling mice at levels of 0.0, 0.3, 0.5 or 0.8% of the diet, with methionine provided at requirement (0.5%) or at twice the requirement (1.0%) level, for 2 wk to assess its effect on the availability of methionine for growth. In another study, ACAP was fed to adult mice at levels of 0.0, 0.4, or 0.6% of the diet, with methionine at 0.5 or 1.0% of the diet, for 2 wk to assess its effect on the availability of methionine for protein synthesis and methylation reactions. The growth rate of weanling mice decreased with increasing dietary ACAP in mice fed 0.5% methionine, but not in those fed 1.0%. Hepatic reduced glutathione (GSH) decreased and plasma glutamic-pyruvic transaminase activity increased in an ACAP dose-dependent manner in weanling mice fed 0.5% methionine. Protein synthesizing ability decreased in adult mice fed 0.5% methionine and 0.6% ACAP. Relative liver weight and liver lipid decreased with increasing dietary ACAP in mice fed methionine at or above requirement. Neither plasma creatinine or muscle creatine was affected by variations in dietary methionine or ACAP. Ingestion of ACAP for a prolonged period of time increased the methionine requirement for growth, maintenance of hepatic GSH level and protein synthesis, but did not affect the methionine requirement for methylation reactions.
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PMID:Prolonged acetaminophen ingestion in mice: effects on the availability of methionine for metabolic functions. 275 11

The mechanism of the periportal (p.p.) toxicity of allyl alcohol (AlOH) was investigated in p.p. and perivenous (p.v.) hepatocytes isolated by digitonin-collagenase perfusion. The distinct origin of the cell preparations was confirmed by the p.p./p.v. ratios of alanine aminotransferase (p.p./p.v. = 1.8), lactate dehydrogenase (1.3) and glutamine synthetase (0.10). The activity of alcohol dehydrogenase (ADH) was not markedly different in p.p. and p.v. cells. Both types of cells oxidized AlOH at a high but equal rate of about 3 mumol/(min.g cells). Concomitantly with rapid oxidation of 0.7 mM AlOH, glutathione (GSH) was depleted by about 95% and its secretion was completely inhibited in both cell types. Although the GSH content was partially restored during a subsequent 3-h incubation, cellular ATP and K+ content gradually decreased and the leakage of lactate dehydrogenase increased in both types of cells. However, the p.p. cells tended to resist AlOH in vitro better, probably due to their 26% higher GSH content after preincubation with L-methionine. Altering the partial pressure of oxygen in physiological range had no effect on the toxicity of AlOH. The results are contrary to the suggestions that the p.p. location of AlOH liver injury is caused by higher ADH activity or higher oxygen tension in the p.p. zone. Rather, the regiospecificity of the injury may be due to rapid uptake and oxidation of AlOH in the p.p. region.
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PMID:Allyl alcohol cytotoxicity and glutathione depletion in isolated periportal and perivenous rat hepatocytes. 283 85

The stability and storage characteristics were studied of 11 bovine enzymes of potential clinical significance, namely, aldolase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, acetylcholinesterase, creatine kinase, gamma glutamyltransferase, glutathione peroxidase (GSH-Px), alpha-hydroxybutyrate dehydrogenase, lactate dehydrogenase and superoxide dismutase (SOD). Enzyme activities in fresh serum were compared with those in plasma containing various anticoagulants including lithium heparin, EDTA and oxalate/fluoride. The same preservatives were assessed for their effects on the whole blood activities of GSH-Px and SOD. Stabilities of enzymes in plasma and serum stored at room (+20 degrees C), refrigerator (4 degrees C) or deep freeze (-20 degrees C) temperatures were also compared. In addition, SOD and GSH-Px activities in samples stored, at the same temperatures, as whole blood or aqueous lysates were monitored.
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PMID:Stability and storage characteristics of enzymes in cattle blood. 286 28

The stability and storage characteristics were studied of 11 ovine enzymes of potential clinical significance, namely, aldolase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, acetylcholinesterase, creatine kinase, gamma glutamyltransferase, glutathione peroxidase (GSH-Px), alpha-hydroxybutyrate dehydrogenase, lactate dehydrogenase and superoxide dismutase (SOD). Enzyme activities in fresh serum were compared with those in plasma containing various anticoagulants including lithium heparin, EDTA and oxalate/fluoride. The same preservatives were assessed for their effects on the whole blood activities of GSH-Px and SOD. Stabilities of enzymes in plasma and serum stored at room (+20 degrees C), refrigerator (4 degrees C) or deep freeze (-20 degrees C) temperatures were also compared. In addition, SOD and GSH-Px activities in samples stored, at the same temperatures, as whole blood or aqueous lysates were monitored. The results are discussed with particular reference to the differences between sheep and cattle.
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PMID:Stability and storage characteristics of enzymes in sheep blood. 286 29


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