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)

Perfluorochemical (PFC) emulsion as a perfusate of liver preservation prior to transplantation was evaluated in continuous hypothermic perfusion for 24 hours followed by orthotopic transplantation in inbred male Lewis rat. Three different contents of PFC emulsion that is, 20% (original Fluosol DA), 10% and 0% PFC solution were prepared as a perfusate. Isolated liver was stored for up to 24 hours using a continuous non-pulsatile perfusion technique of closed circuit with each perfusate. Gas content, GOT, GPT, LDH, potassium and glucose of the perfusate were measured. Oxygen consumption of perfused liver was higher in PFC emulsion than non PFC perfusate. Biochemical analysis of perfusate suggested that liver was preserved best in 10% PFC emulsion. Histological findings, especially, acid phosphatase staining, showed better result in PFC groups. One week survival rates after liver graft were 4/6 (66.7%) in 10% PFC solution, 1/6 (16.7%) in 20% and 0/6 (0%) in 0% solution. In spite of the highest oxygen consumption of perfused liver in early phase, 20% PFC emulsion did not bring the good preservation of perfused liver because of impaired circulation due to higher viscosity in low temperature. Ten percent PFC solution is considered the best in hypothermic preservation of the liver.
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PMID:[Perfluorochemical emulsion as a perfusate in 24-hour liver preservation prior to transplantation in the rat]. 305 66

This study demonstrates that the exposure of phenobarbitone-treated rats to halothane at an oxygen concentration of either 10% or 14% results in marked decreases in cytochrome P-450 content and aminopyrine demethylase activity in animals sacrificed from 1 to 48 hr post-exposure. The alterations observed in the hepatic mixed function oxidase system were accompanied by increases in serum alanine aminotransferase (ALT), ornithine carbamyl transferase (OCT) and changes in liver pathology. However, the minor changes in cytochrome P-450 content and aminopyrine demethylase activity observed following exposure of enzyme-induced rats to halothane under normoxic conditions (i.e. 21% oxygen) were not of a sufficient magnitude to lead to hepatic cell necrosis. Halothane administration in the absence of phenobarbitone pretreatment (i.e. 21% oxygen) or during hypoxia alone (i.e. either 10% or 14% oxygen) did not result in any systematic changes in the parameters assayed. The results suggest that cytochrome P-450 may catalyse its own inactivation by virtue of greater free radical production under conditions which favour the non-oxygen dependent metabolism of halothane. The impairment in microsomal function as evidenced by decreases in cytochrome P-450 and aminopyrine demethylase activity are considered to occur as a primary consequence of the reductive metabolism of halothane. Data are presented which support the concept of the initiation of hepatic damage occurring during the period of anaesthesia with halothane.
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PMID:Changes in rat hepatic microsomal mixed function oxidase activity following exposure to halothane under various oxygen concentrations. 310 40

Oxygen free radicals have been implicated in the pathogenesis of postischemic liver injury. High-dose superoxide dismutase (SOD), a radical scavenging enzyme, has been investigated in a rat model of liver ischemia reperfusion by biochemical monitoring. Blood vessels to the median and left lobe were clamped for 1 h and then reperfusion was allowed. The indices used were serial venous blood levels of AST, ALT, calcium, and ATP determination in liver tissue. In SOD-treated animals (7,5000 U i.v.) a significant attenuation of the rise in enzyme levels was observed as well as the absence of the decrease in calcium level in the early phase after reperfusion as compared with control rats, and furthermore ATP restoration was significantly increased.
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PMID:Effect of superoxide dismutase on liver ischemia-reperfusion injury in the rat: a biochemical monitoring. 322 31

Hepatic damage was induced in phenobarbitone pretreated male Fischer 344 rats by the administration of 1% halothane in 14% oxygen for either 1 or 2 hours. Ethane production during the exposure period was not significantly different between the halothane and non-halothane exposed groups. Animals were sacrificed 1, 2, 6 and 24 hrs from commencement of anaesthesia and the hepatic microsomal fraction analyzed for diene conjugates, lipid hydroperoxides, total lipid content and fatty acid composition. Animals exposed to halothane and sacrificed at 2 and 24 hrs had significantly elevated levels of diene conjugates (P less than 0.05), while lipid hydroperoxide concentration and serum alanine aminotransferase increased in only those animals sacrificed at 24 hrs. Alterations in total lipid content and hepatic microsomal fatty acid composition were not observed in animals sacrificed after 1 and 2 hrs. A significant reduction in total lipid and arachidonic acid content occurred only in those animals sacrificed 24 hrs after exposure, however a concomitant increase in the saturated fatty acid fraction was not observed. It is proposed that alterations in fatty acid composition in vivo and evidence of lipid peroxidation occur as a result of cell death rather than an initiating event in halothane induced hepatic necrosis in rats.
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PMID:Halothane induced hepatic necrosis in rats: the role of in vivo lipid peroxidation. 323 93

The relationship between transplant viability and liver function has been examined. Wistar rat livers were preserved at 4 degrees C for increasing intervals and then transplanted into Wistar rat recipients. Two critical times were identified, the longest preservation period with 100% transplantation success (4 hr) and the shortest preservation period with 100% transplant failure (8 hr). The comparable critical times were also identified in livers preserved at 37 degrees C (1 hr and 2 hr). Liver functions were studied by the isolated perfused liver technique in other rat livers stored at 4 degrees C or 37 degrees C for the critical times. Two liver function tests, AST and LDH concentration in perfusate, discriminated between viable and nonviable livers across as well as within preservation groups. AST gave the best separation between viable and nonviable livers. Some functions such as ALT concentration in perfusate separated viable from non viable allografts only within preservation groups. Other liver functions were more sensitive to preservation temperature than allograft viability. Oxygen consumption after cold preservation for either critical time was about twice control levels. Urea production was far below control levels in warm-preserved livers but almost normal in cold-preserved livers. Our results indicate that AST release into perfusate can be used as a screening technique to optimize preservation methods, reserving transplantation for confirming the most promising results.
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PMID:Markers of allograft viability in the rat. Relationship between transplantation viability and liver function in the isolated perfused liver. 331 44

Maximal activities of rat skeletal muscle mitochondrial citrate synthase (CS), malate dehydrogenase (MDH), and alanine aminotransferase (ALT), as well as several other mitochondrial enzymes involved in various metabolic functions were significantly suppressed after a single bout of acute or exhaustive treadmill running. This enzymatic "down regulation" was maintained 24 and 48 h post exhaustion, especially in the untrained rats. Neither muscle cytosolic nor hepatic enzymes exhibited down regulation after exercise. Proteolysis was increased with exercise as assessed by the clearance of [3H]leucine previously incorporated into the proteins of the rats. Decreased CS, MDH, and ALT activities correlated with a significant loss of mitochondrial total protein sulfhydryl (r = 0.67, 0.68, 0.59, respectively, P less than 0.001) in untrained rats and both CS and MDH could be partially restored by incubation with dithiothreitol. Endurance-tested untrained and trained rats had significantly higher glutathione peroxidase (GPX) activity in both muscle mitochondria and cytosol which correlated significantly with endurance time (r = 0.70 and 0.74, respectively). It is concluded that enzymatic down regulation is not caused by proteolysis alone; i.e., peroxides and oxygen free radicals produced in prolonged exercise may alter the intramitochondrial redox state by oxidizing free thiols that may be required at active sites of these enzymes. Training may enhance the ability of the muscle to resist the toxic oxygen species by increasing GPX activity.
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PMID:Enzymatic down regulation with exercise in rat skeletal muscle. 336 59

Oxygen-derived free radicals might play a role in the injury produced by reperfusion of ischemic organs. Since the generation of reactive oxygen species results in an increased formation of glutathione disulfide, we have attempted to document an oxidant stress during reperfusion of ischemic liver by following the hepatic production of glutathione disulfide in vivo and in the perfused rat liver. Following partial hepatic ischemia of 120 min duration, the plasma concentration of glutathione disulfide gradually increased from 0.8 +/- 0.1 to 9.1 +/- 1.6 microM (mean +/- S.E., n = 6) after 1 hr of reperfusion. The plasma concentration of reduced glutathione increased only 2-fold from 21.4 +/- 2.4 to 38.1 +/- 3.4 microM. The rise in plasma glutathione disulfide was higher with increasing duration of ischemia from 30 to 120 min and was associated with a gradual increase in hepatic glutathione disulfide. The hepatic origin of glutathione disulfide was documented in the perfused rat liver where the release of glutathione disulfide increased gradually during reperfusion following 90 min of warm ischemia from 1.0 +/- 0.1 to 2.6 +/- 0.5 nmole per min per gm liver at 30 min after onset of reperfusion. The administration of allopurinol, an inhibitor of xanthine oxidase, did not decrease the release of glutathione disulfide (29.9 +/- 3.8 nmoles per gm in controls vs. 44.7 +/- 10.0 nmoles per gm in 30 min with allopurinol) and ALT (3.3 +/- 1.4 units per gm in controls vs. 2.6 +/- 0.8 units per gm in 30 min with allopurinol). Our studies document an oxidant stress associated with reperfusion of ischemic liver.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxidant stress during reperfusion of ischemic liver: no evidence for a role of xanthine oxidase. 337 74

Acute liver dysfunction was analyzed in 15 patients who received a modified Fontan operation for single ventricle in nine (atrial isomerism, seven) and tricuspid or mitral atresia in six. Nine patients had elevation of serum glutamic-pyruvic transaminase levels above 1000 U/L during the first week. As an analysis of postoperative liver function during the first week, the highest values of serum glutamic-pyruvic transaminase and total bilirubin and the lowest prothrombin time were scored from 0 to 4 within each parameter, and totaled to give a liver dysfunction score. The liver dysfunction score was 0 to 2 (no or trivial injury) in five patients, 3 to 5 (mild) in two, and 6 to 11 (moderate or severe) in eight (53.3%). The group operated on for single ventricle had a higher incidence (67%) of a liver dysfunction score of 6 or higher than the other group (33%). A multivariate analysis for the prediction of the liver dysfunction score mainly from early postoperative hemodynamics showed the highest correlation with cardiac index, followed by urine output, systolic arterial pressure, and central venous pressure. One patient required plasmapheresis. Four died early (less than 1 month); three of these had a liver dysfunction score of 6 or higher. Those with scores of 6 or above had higher serum glutamic-pyruvic transaminase levels at 1 month after operation than those with scores less than 5. In three patients (single ventricle), hepatic venous oxygen saturation was monitored and showed a marked decrease to below 20% with subsequent acute liver dysfunction. These results indicate that acute liver dysfunction appears to occur in patients with complex lesions after a modified Fontan operation from possible hepatic hypoperfusion and that low cardiac output may be more crucial than high central venous pressure alone.
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PMID:Acute liver dysfunction after modified Fontan operation for complex cardiac lesions. Analysis of the contributing factors and its relation to the early prognosis. 339 44

Stroma-free hemoglobin (SFH) is advocated as an oxygen-transporting resuscitation solution. Hemoglobin has been shown to enhance endotoxin lethality when given intraperitoneally. It is possible that SFH could interact with endotoxin when used as an oxygen-transporting resuscitation system for trauma victims with contaminating wounds. To assess the effects of these two agents when given intravascularly, rabbits were infused with SFH (1.75 gm/kg) or albumin (controls; 1.75 gm/kg) with and without endotoxin. Two doses of endotoxin were used. At 14.5 ng/kg of Salmonella enteritidis endotoxin, no effect was seen in the albumin group. However, 50% of the hemoglobin group died. At 14.5 micrograms/kg, the albumin group showed hematologic alterations, but all animals lived. All SFH-treated animals died at the higher endotoxin dose. SFH alone caused cardiac abnormalities (bradycardia in 100%, sinus arrhythmias in 30%, and ventricular arrhythmias in 20%), liver abnormalities (necrosis in 40% and 240% increase in alanine aminotransferase activity by 6 hours), and intravascular thrombi (30%). The only hemoglobin-induced abnormality that was more frequent in the presence of endotoxin was ventricular arrhythmias (up to 75% of animals). Thrombin times were approximately 20% larger in all SFH groups compared with the albumin groups. By 6 hours after infusion, endotoxin prolonged the thrombin time even further, despite the lack of fibrinogen consumption. This study shows that endotoxin and SFH exert synergistic toxicity when SFH is given in a clinically relevant dose for an oxygen-transporting resuscitation system. Only minute quantities of endotoxin are needed to produce this phenomenon. We hypothesize that this synergism is endotoxin enhancement of hemoglobin toxicity.
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PMID:Synergistic toxicity of endotoxin and hemoglobin. 352 17

Twelve dogs were infused with 10(10) Escherichia coli/kg of body weight through a portal vein catheter over a 1-hour period; 6 dogs were treated with flunixin meglumine (1 mg/kg) 15 minutes after the infusion had begun. Six dogs (controls) were infused with a comparable volume of sterile saline solution over the same period. Over a 4-hour monitoring period, nontreated septicemic dogs developed systemic hypotension, decreased cardiac output, increased portal pressure, increased serum alanine transaminase values, increased extravascular liver water, increased liver glycogen depletion, and decreased arterial oxygen tension compared with control dogs. Accumulations of polymorphonuclear leukocytes and E coli were found in the livers and lungs of septicemic dogs. Flunixin meglumine treatment prevented systemic hypotension and hypoxemia, reversed the early but not the late stages of portal hypertension, and decreased E coli concentrations in the lungs. Other effects of treatment were not noticed.
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PMID:Escherichia coli-induced lung and liver dysfunction in dogs: effects of flunixin meglumine treatment. 354 2


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