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)

The discovery of cyclosporine has had a significant impact on preventing the rejection of transplanted organs in humans. In this study, we present another positive aspect of cyclosporine. Rats were pretreated with cyclosporine (10 mg/kg, i.v.), or untreated. After 2-hr ischemia or 1 hr of reperfusion following 2-hr ischemia, livers were isolated and liver adenine nucleotide concentrations were determined. Liver mitochondria were prepared and their function was estimated polarographically. Leakage of AST, ALT, LDH, and adenine nucleotides into the hepatic vein just after reperfusion was also measured. Cyclosporine treatment did not affect ischemia-induced mitochondrial dysfunction, nor did it prevent the associated decrease in adenosine triphosphate concentration. However, treatment with cyclosporine accelerated the recovery of mitochondrial function and of tissue adenosine triphosphate concentrations. Cyclosporine treatment also mitigated leakage of AST, ALT, LDH, and adenine nucleotides after reperfusion. These results indicate that cyclosporine shows a potent protective effect on ischemia-reperfusion-related liver injury.
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PMID:Beneficial effects of cyclosporine on postischemic liver injury in rats. 173 23

In a clinical setting, the effect of Eurocollins (EC) and University of Wisconsin solution (UW) on liver grafts were studied in the early reperfusion phase of liver transplantation. Blood samples were drawn before and after declamping of the portal vein in a group of 11 transplants with EC-perfused livers, and a group of 12 transplants with UW-perfused livers. Parenchymal damage was assessed by the LDH, AST, and ALT, and purine degradation by measuring the uric acid levels. Metabolic function was determined by the serum bile acids and the plasma amino acids, i.e. (valine + leucine + isoleucine)/(phenylalanine + tyrosine) ratio. Donor and pretransplant recipient parameters were almost identical. The cold ischemia time of both groups differed significantly. The results show the following: a significant difference between both the LDH and the uric acid levels in the two groups was revealed, with a smaller increase of the LDH levels and no increase of the uric acid levels in the UW group. Metabolic activity, as measured from the bile acids and the amino acid profile in the peripheral blood, was identical in both groups. We conclude that both EC-stored and UW-stored liver grafts show immediate metabolic function after reperfusion. The amount of metabolic function was equal in both groups, notwithstanding longer cold ischemia time in the UW group. In addition, more parenchymal damage occurred in the EC group.
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PMID:Cellular damage and early metabolic function of transplanted livers stored in Eurocollins or University of Wisconsin solution. 180 31

Although several studies suggest that hepatic graft failure after cold ischemia results from nonparenchymal cell damage, other data indicate that hepatocellular ATP content is significantly correlated with the transplantation success rate. In this study, we have conducted a systematic investigation of various aspects of cell viability and function of isolated hepatocytes stored at 4 degrees C for 24 and 48 hr in either University of Wisconsin solution or Hanks' HEPES buffer, a control solution clinically unsuitable for organ preservation. After 24 hr, hepatocytes stored in Hanks' HEPES buffer had viability (measured by trypan blue exclusion and ALT and lactic dehydrogenase leakage), transport function (measured by 22Na+ and [3H]taurocholate uptake) and cell size similar or only slightly altered when compared with freshly isolated and University of Wisconsin solution-stored hepatocytes. ATP content was decreased in both groups; however, the reduction was much greater in Hanks' HEPES buffer-stored cells. Furthermore, ATP regenerating capacity was greatly reduced in Hanks' HEPES buffer- stored but not in University of Wisconsin solution-stored hepatocytes. By 48 hr viability and function of Hanks' HEPES buffer-stored hepatocytes were decreased; University of Wisconsin solution afforded partial protection. When examined by light and electron microscopy, cells stored in both University of Wisconsin solution and Hanks' HEPES buffer for 24 hr appeared essentially normal except for the presence of numerous membrane blebs in the Hanks' HEPES buffer group. Tissue sections of livers preserved in Hanks' HEPES buffer but not in University of Wisconsin solution revealed the presence of extensive amounts of blebs in the sinusoidal lumen and loss of endothelial elements.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Functional and morphological features of isolated hepatocytes preserved in University of Wisconsin solution. 186 Jun 90

Cellular damage of various organs by ischemia following reperfusion is assumed to be at least in part due to lipid peroxidation in biomembranes, and oxygen-derived free radicals play a major role. The level of lipid peroxides in liver tissue increased during 90-min ischemia. When reflow of hepatic blood was allowed, a greater increase in the lipid peroxides was observed. Similar increases were obtained in several serum markers (GOT, GPT and LDH) during the period of ischemia or ischemia-reperfusion. In addition, levels of cytochrome p-450 and NADPH cyt. c reductase activity decreased in proportion to the decrease in microsomal proteins during ischemia or ischemia-reperfusion. On the other hand, superoxide dismutase in blood was significantly increased by ischemia-reperfusion. Rats died within 2 days after liver ischemia of 90 min, while all animals subjected to 30-min ischemia survived. Histopathological examinations indicated that extensive coagulation with erythrocytes occurred and the extent was dependent on the time of ischemia. The liver injury by ischemia-reperfusion could be a useful experimental model for studying liver injury induced by free radicals, for developing hepatoprotective drugs, or for investigating liver transplantation.
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PMID:[An injury of the liver caused by ischemia-reperfusion in rat liver]. 190 28

Iron-dependent oxy radicals have been implicated in reperfusion injury. Although the iron chelator desferoxamine (DFO) is beneficial, its hemodynamic effects and short vascular retention limit its use in vivo. We tested whether DFO conjugated to a high-molecular-weight starch might ameliorate in vivo hepatic microvascular injury without adverse side effects following 120 min of ischemia. Prior to reperfusion, conjugated DFO (100 mg/kg), vehicle (Veh), or saline (I/R) was administered. After 90 min of reperfusion, blood was collected for serum transaminase determination (ALT; U/liter), and fluorescein-albumin was injected to label perfused microvessels, which were quantified in frozen sections by a point-count technique. Tissue edema was estimated by wet to dry weight ratios (W/D). Reperfusion results in hepatocyte injury (rise in ALT and W/D) and a 30% loss of perfused microvessels. Intravenous administration of conjugated DFO produces no significant change in systemic hemodynamics, whereas both ALT and tissue edema were decreased by approximately 50%. Moreover, perfused microvessels were restored virtually to nonischemic control levels. Enhanced perfusion and attenuated cell injury with DFO suggest that microvascular failure and resultant cell death are mediated, at least in part, by iron-dependent mechanisms in reperfusion.
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PMID:Conjugated desferoxamine attenuates hepatic microvascular injury following ischemia/reperfusion. 193 29

During operation, biopsies from the gastrocnemius muscle and, in some cases, from the sartorius muscle were taken from 32 patients with peripheral arterial occlusive disease and from 5 subjects with normal peripheral circulation. In patients with inadequate circulation only during exercise, when compared with the control group, increased activities of enzymes involved in oxidative metabolism (malate dehydrogenase, nicotinamide adenine dinucleotide phosphate-dependent isocitrate dehydrogenase, cytochrome C oxidase, creatine kinase), in amino acid metabolism (asparate aminotransferase, alanine aminotransferase), and in anaerobic glycoysis (lactate dehydrogenase) were found. In patients with circulatory disturbances that manifested themselves already at rest, enzyme activities were, with the exception of LDH, lower than those of patients with exclusively exercise-related insufficiency. By means of intraindividual comparisons with the corresponding enzyme activities in the sartorius muscle, the author was able to show that the changes found were not simply the result of differences in training conditions. The diminished concentrations of energy-rich phosphate are an expression of the anaerobic metabolic state in patients with inadequate circulation at rest. It is concluded that chronic ischemia of muscle leads to changes in the energy metabolism of the cell. In the presence of more nearly adequate circulation at rest, the portion of oxidative potential of the total energy metabolism increases. In contrast, if there is an inadequate circulation at rest, the mainly anaerobic glycolysis becomes quantitatively predominant.
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PMID:Investigations on the biochemical characteristics of chronically underperfused muscle. 201 45

Oxygen free radicals have been implicated as mediators of ischemia/reperfusion injury in a variety of organs. We investigated the role of oxidative injury and endogenous hepatic glutathione (GSH) in liver cell injury associated with complete hepatic ischemia and reperfusion. Forty-five minutes of complete hepatic ischemia followed by reperfusion caused an increase in serum GPT and a fall in hepatic GSH but no increase in hepatic lipid peroxidation products. Chemical depletion of hepatic GSH with diethyl maleate did not cause hepatocellular injury but augmented hepatic ischemia/reperfusion-induced SGPT release and promoted lipid peroxidation. Pretreatment with the selective, membrane-permeable oxygen radical scavenger dimethyl sulfoxide protected against the ischemia/reperfusion-induced drop in hepatic GSH but did not reduce SGPT release in normal rats. In rats sensitized to oxidative injury by depletion of endogenous GSH with diethyl maleate the oxygen radical scavenger protected against ischemia/reperfusion-induced lipid peroxidation and reduced the release of SGPT. These findings suggest that the rich hepatic supply with endogenous GSH has a crucial role in the protection against oxygen radical injury following short periods of total hepatic ischemia. Oxygen radical injury only occurs after depletion of these endogenous GSH stores.
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PMID:Oxygen free radicals and glutathione in hepatic ischemia/reperfusion injury. 202 Jan 91

In the majority of patients with intestinal infarction, it is generally agreed that the occlusion of mesenteric arteries or vein is the primary etiologic factor; however, some showed no evidence of thrombosis, embolization or vasculitis as the causative factor. In many patients, this particular type of infarction is the terminal event of the episode. From October 1977 to December 1986, 24 patients with mesenteric infarction were investigated following cardiovascular surgery in our institute. Among them, 15 were diagnosed with organic vascular occlusion; however, the other 9 showed no evidence of thromboembolism or any other organic vascular occlusive lesion of mesenteric vessels and were diagnosed as non-occlusive mesenteric infarctions. All of these patients were in severe cardiac failure (LOS) postoperatively. There was no typical symptom, although abdominal fullness and diarrhea were the major and consistent findings. In blood chemical analysis, the enzymatic levels such as serum GOT, LDH and CPK were significantly elevated and discrepancy between serum GOT and serum GPT was observed. In this clinical situation, it was difficult to establish a correct diagnosis mainly because of the few signs and symptoms present relating to the mesenteric infarction. On the other hand, when the correct diagnosis was made, these patients were too critically ill to be treated conservatively. The outcome of these patients was grave and all of them died which showed 100% of mortality rate. The conservative management did not produce favorable progress, which accelerated LOS and prevented patients from recovering from cardiac failure. The aggressive surgical approach to this particular type of acute mesenteric ischemia might have offered an improved prognosis from these catastrophic events.
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PMID:[Non-occlusive mesenteric infarction following cardiovascular surgery]. 202 11

Verapamil, a calcium channel blocker, improves myocardial preservation during cold cardioplegia and protects against renal damage during periods of warm and cold ischemia. To determine if verapamil could prevent ischemic damage to livers during and after cold storage, harvested rat livers were flushed with either University of Wisconsin (UW) solution or UW solution with 25 mg/liter verapamil. Twenty rats were used in each group. After 24 hr of storage at 4 degrees C, livers were perfused with oxygenated blood through the portal veins for 2 hr at 37 degrees C and pH 7.4. Liver enzymes, electrolytes, and perfusate flow rate were determined at 30-min intervals. At 90 min of perfusion, the verapamil group of livers had less elevation of AST (110 +/- 17 IU/liter vs 172 +/- 25 IU/liter, P less than 0.05), ALT (115 +/- 21 IU/liter vs 210 +/- 34 IU/liter, P less than 0.05), and LDH (962 +/- 170 IU/liter vs 1452 +/- 253 IU/liter, NS). Verapamil livers produced more bile than controls (6.9 +/- 1.9 microliters/g vs 2.3 +/- 1.7 microliter/g, P less than 0.05) and maintained a higher portal flow rate throughout the perfusion. Both groups showed similar reduction in liver weights after storage (3.9 +/- 0.9% vs 2.8 +/- 0.7%) and required the same amount of bicarbonate for correction of acidosis during perfusion (2.6 +/- 0.2 mM vs 2.8 +/- 0.2 mM). Light microscopic exam after perfusion showed hepatocyte damage in 30% of control livers, but 0% of verapamil livers. We conclude that verapamil-treated rat livers showed less damage and better function upon reperfusion after 24 hr of cold storage. This agent may be clinically useful as an additive to the UW preservation solution for livers.
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PMID:Verapamil improves rat hepatic preservation with UW solution. 205 66

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


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