Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to examine the role of Kupffer cells in polymorphonuclear neutrophils (PMN) activation and infiltration after severe total hepatic ischemia. Male rats pretreated with either normal saline (NS group; n = 58) or gadolinium chloride (7 mg/kg; GC group, n = 57) for 2 days were subjected to 90 min total hepatic ischemia. In addition to 7-day survival rate, aspartate aminotransferase (AST), PMN liver infiltration, plasma myeloperoxidase (MPO), and interleukin-1 (IL-1) levels were serially measured from the end of ischemia to 360 min after reperfusion. Survival rate of the GC group significantly improved to 67% (P < 0.01), whereas that of the NS group remained at 20%. Extremely high AST levels (5,372 +/- 231 IU/liter) were obtained in the NS group, which correlated with the degree of hepatic necrosis. Very high IL-1 (270.3 +/- 91.2 pg/ml) and MPO (1.7 +/- 0.4 U/ml) levels were also seen in the NS group. The GC group significantly inhibited increases in AST, IL-1, and MPO levels as well as PMN infiltration in the liver compared to the NS group (P < 0.05). Our study demonstrated that Kupffer cell activation has an important role in the development of reperfusion injury after total hepatic ischemia through IL-1 release, and PMN activation and infiltration.
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PMID:Role of Kupffer cells in neutrophil activation and infiltration following total hepatic ischemia and reperfusion. 805 66

Although the liver is relatively resistant to normothermic ischemia, prolonged periods of inflow occlusion have produced evidence of hepatocyte injury. We have developed an animal model of liver ischemia using the pig and maintaining subtotal inflow (hepatic artery and portal vein) occlusion, allowing mesenteric portal decompression via patent portal veins through the caudate lobe, obviating the need for portosystemic shunting. This produced biochemical [aspartate transaminase (AST), lactate dehydrogenase (LDH)] and histopathologic evidence, using a microscopic grading system, of hepatocyte necrosis after 2 hr of normothermic ischemia. By administration of prostaglandin E1 (PGE1) prior to and during inflow occlusion, we have produced a statistically significant reduction in LDH (1085.9 +/- 413.5 U/liter compared to 669.1 +/- 161.4 U/liter) and AST (236.5 +/- 80.4 U/liter compared to 85.1 +/- 39.7 U/liter) (P < 0.05) between control and PGE1 animals 24 hr after reperfusion. Moreover, using the blinded microscopic grading system for hepatocellular necrosis, we have found significantly less (2.86 +/- 0.90 compared to 1.57 +/- 1.13, P < 0.01) necrosis when control and PGE1 animals were compared. Our experimental model supports the hypothesis that PGE1 exerts a cytoprotective effect during prolonged normothermic hepatic ischemia but does not aid in elucidating a mechanism for this effect.
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PMID:Evidence for cytoprotection by prostaglandin E1 with normothermic hepatic ischemia. 815 23

Cardiopulmonary and other organ dysfunction often occurs after operation on the descending thoracic aorta. Though there are multiple causes of organ dysfunction in this setting, free radical injury may play a prominent role. Xanthine oxidoreductase, an enzyme that generates oxidants after exposure to ischemia, could be released from ischemic liver and intestine during reperfusion. To test this hypothesis, we created aortic occlusion in eight rabbits for 40 minutes by inflation of a 4F Fogarty balloon catheter in the descending thoracic aorta. Eight sham-operated rabbits served as a control group. Two hours of reperfusion followed removal of the balloon catheter. Hemodynamic and acid-base status were maintained near baseline values during reperfusion. Plasma samples were obtained for determination of the activity of the hepatocellular enzymes xanthine oxidoreductase, aspartate aminotransferase, alanine transferase, and lactate dehydrogenase. Plasma xanthine oxidoreductase activity increased significantly (p < 0.001) during reperfusion (729 +/- 140 microU/ml, mean +/- standard error of the mean) compared with baseline (132 +/- 18 microM/mL). The other enzymes followed a similar pattern of release. We report the release of xanthine oxidoreductase in an animal model that simulates the situation of human thoracic aorta operations. The oxidants produced by the circulating xanthine oxidoreductase observed during reperfusion would likely be toxic to vascular endothelium, potentially contributing to multiple organ dysfunction.
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PMID:Xanthine oxidoreductase release after descending thoracic aorta occlusion and reperfusion in rabbits. 817 64

Glycine has been shown to protect renal tubule cells and hepatocytes from ischemia, ATP depletion, and cold storage injury. Glycine may be a useful additive to organ preservation solutions or suppress reperfusion injury by infusion into recipients of liver transplantation. In this study, the effects of glycine on survival and postoperative liver injury were studied in the rat and dog orthotopic transplant model. Rat livers preserved for 30 hr in the University of Wisconsin (UW) solution were 50% viable (3 of 6 survivors for 7 days). When glutathione was replaced by 10 mM glycine, survival increased to 100% (6 of 6). There was a significant reduction in hepatocellular injury at the end of preservation (lactate dehydrogenase [LDH] in the pretransplant flush-out of the liver was lower in the glycine group) and after transplantation (serum LDH concentration 6 hr after transplant was lower in the glycine group). In the dog, omission of glutathione from the UW solution resulted in 33% survival (48-hr preservation model) versus 100% survival with glutathione. Replacing glutathione in the UW solution by glycine did not improve survival (33% after 48 hr of preservation). However, when glycine was given to recipients of livers preserved in the UW solution for 24 or 48 hr, there was a decrease in the degree of hepatocellular injury. After 48 hr of preservation, peak aspartate aminotransferase, alanine aminotransferase, and LDH were reduced by about 45-55% when glycine was given to the recipient. Although the differences, with and without glycine treatment of the recipients, did not reach statistical significance, there was a noticeable reduction in hepatocellular injury with glycine. There was 100% survival of dogs in the groups that received livers preserved with the UW solution plus or minus glycine infusion. Hepatamine, a parenteral nutrition solution containing glycine and other amino acids increased hepatocellular injury (higher concentrations of aspartate aminotransferase, alanine transferase, and LDH versus control 48-hr preserved livers), although all dogs survived. This study shows that glycine is cytoprotective when administered to recipients of livers preserved for 24 or 48 hr and suppresses hepatocellular injury, as reflected in a reduction in the concentration of serum enzymes. However, the differences, with and without glycine, were, at best, marginal and further studies are needed to determine whether glycine would make a significant improvement in liver preservation and prevent primary nonfunction.
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PMID:Effect of glycine in dog and rat liver transplantation. 821 99

The purposes of this study were to clarify the role of neutrophilic proteases in the pathogenesis of hepatic ischemia/reperfusion injury and to determine whether urinary trypsin inhibitor (UTI) pretreatment attenuated liver ischemia/reperfusion injury in rats. Livers from male Sprague-Dawley rats were subjected to 90 min of no-flow warm ischemia followed by 120 min of reperfusion. Rats were divided into a UTI group and a control group. In the control group, 120-min reperfusion of the liver produced a significant increase in myeloperoxidase activity, a significant decrease in ATP and energy charge, and a marked increase in the serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels. In the UTI group, the myeloperoxidase activity was significantly attenuated (P < 0.01), ATP and energy charge were significantly improved (P < 0.01 and P < 0.05, respectively), and the elevation in serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase was also markedly suppressed (P < 0.05, P < 0.01, and P < 0.05, respectively) compared with the control group. Sections through the livers of control rats showed severe hepatocyte necrosis with neutrophil infiltration. In the UTI group, there was slight congestion and hepatocyte necrosis. The survival rate after 90-min liver ischemia was significantly improved compared with that in the control group (P < 0.05). The results of this study suggest that pretreatment with UTI significantly attenuates liver reperfusion injury, perhaps by inhibiting neutrophil proteases.
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PMID:Effect of protease inhibitor on ischemia/reperfusion injury of the rat liver. 827 98

It is well recognized that current selection criteria used to assess liver grafts before implantation are inaccurate and correlate poorly with graft outcome. A bench or laboratory-based test that could indicate the extent of liver injury immediately before implantation would be a valuable adjunct to clinical assessment. Hyaluronic acid (HA) and creatine kinase (BB component; CK-BB) levels in the caval effluent after liver perfusion have been suggested as indicators of preservation injury. Our objective was to investigate the relevance of preserved liver effluent HA and CK-BB as a predictor of early graft function. Perfused liver effluent HA and CK-BB levels were measured. Graft function was measured in terms of peak serum aspartate transaminase and its level on day 5 postoperatively as well as peak bilirubin level and prothrombin time. The cold ischemia time (CIT) was recorded. Statistical comparisons were made among HA level, CK-BB level, CIT, and graft function parameters. The study was conducted at The Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom. Fifty patients undergoing OLT were studied. HA level was measured in 50 patients and CK-BB level in 30 patients. The main outcome measures were graft function and graft outcome. The graft function data are grouped according to effluent HA levels above or below 400 micrograms/L. Thirteen patients (26%) had a level below 400 micrograms/L and the remaining 37 (74%) were above this threshold. There were no significant differences between the groups for these indicators of graft function. There was no difference between the 2 groups for CIT. The overall median HA level was 1212 micrograms/L (range 39-4000 micrograms/L). The median total CK activity in the perfusate was 302 IU/L (range 118-1155 IU/L). The proportion of CK-BB activity from this total was 146 IU/L (8-641 IU/L), or 48% of the total CK activity. In a multiple regression analysis with CK-BB activity as the dependent variable, there was no demonstrable numerical relationship to graft function. In a separate multiple regression analysis similar results were obtained for HA. We conclude that the level of HA or CK-BB levels should not be used in determining the suitability for implantation of a harvested hepatic allograft.
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PMID:Can effluent hyaluronic acid or creatine kinase predict sinusoidal injury severity after cold ischemia? 827 99

Platelet-activating factor (PAF), one of the chemical mediators related to inflammation reaction, is also involved in the pathologic state induced by endotoxin or ischemia. PAF antagonist has been reported to block the action of PAF and protect cells from its deleterious effects. The effects of a PAF antagonist, CV-6209, were evaluated in this study by means of a partial liver ischemia model, in which ischemia was induced by clamping only part of the liver without causing intestinal congestion. This model allowed the study of ischemic liver injury without influence from other organs. After 30, 60, and 90 minutes of ischemia, the bile flow, ATP level, and energy charge of the ischemic lobes were compared for the effects with and without CV-6209. After 60 minutes of ischemia, those that had received CV-6209 showed more bile production and higher ATP level and energy charge, with values of 0.25 +/- 0.05 ml/hr, 3.9 +/- 0.9 nmol/mg dry liver weight, and 0.61 +/- 0.02, respectively. In contrast, the values for the control group were 0.05 +/- 0.05 ml/hr, 1.7 +/- 0.8 nmol/mg dry liver weight, and 0.43 +/- 0.08, respectively. Other liver function tests (aspartate aminotransferase and lactate dehydrogenase levels) could also be improved if an appropriate dose of PAF antagonist were administered. The results imply that PAF, as has been suggested in other studies on ischemic injury, plays a role in liver ischemia and that its deleterious effects can be blocked by PAF antagonist. We conclude that the PAF antagonist offers promise in the field of liver surgery, including liver transplantation, as a means of protecting the liver from ischemic injury.
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PMID:Protective effect of platelet-activating factor antagonist on ischemia-induced liver injury in rats. 841 92

Studies were made on the effects in rat lungs of aerobic and anaerobic conditions on the intracellular levels of adenosine triphosphate and its related metabolites, the releases of intracellular enzymes, and the secretion of pulmonary surfactant. After warm ischemia for 120 min, the ATP content of lungs inflated with air was significantly higher (8.0 +/- 1.2 mumol/g dry weight) than those of deflated lungs and lungs inflated with nitrogen (0.8 +/- 0.7 mumol/g dry weight and 2.0 +/- 0.7 mumol/g dry weight, respectively; P < 0.001). The amounts of intracellular enzymes, such as lactate dehydrogenase, cytosolic and mitochondrial aspartate aminotransferase, and protein in the bronchoalveolar lavage fluid (BALF) of air-inflated lungs were significantly less than those in BALFs of deflated and nitrogen-inflated lungs (P < 0.001). The BALF-contents of dipalmitoyl phosphatidylcholine (DPPC), the main component of alveolar surfactant of aerobic and anaerobic ischemic lung were, however, similar. During 120-min warm ischemia after lavage, air-inflated lungs secreted significantly more DPPC into the alveolar space than nitrogen-inflated lungs did (P < 0.001). We conclude that cell membranes in the lungs are damaged under anaerobic conditions, but that inflation of ischemic lungs with air is effective for protecting them from cell injury and for maintaining the intracellular level of ATP and the ability of the cells to secrete pulmonary surfactant.
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PMID:Attenuation of warm ischemic injury of rat lung by inflation with room air--assessment of cellular components and the surfactant in the bronchoalveolar lavage fluid in relation to changes in cellular adenosine triphosphate. 842 61

Superoxide anion radical (O2-) is one factor related to ischemia/reperfusion injury to the liver. The sites of O2- production and injury have yet to be determined. Superoxide dismutase (SOD), a specific scavenger for O2-, has an inhibitory effect on injury caused by O2-. SOD is of low molecular weight; hence, it has a short half-life in the circulating blood. Mannosylated SOD is taken up in sinusoidal endothelial cells of the liver by receptor-mediated endocytosis. In rats with an occluded inflow against 70% of the liver for 30 min followed by reperfusion there were elevations of serum aspartate aminotransferase and alanine aminotransferase, and lipid peroxide concentrations in liver tissue were significantly inhibited by intravenous administration of mannosylated SOD compared to treatment with normal saline. Electron microscopic examination showed that mannosylated SOD protected against damage to the sinusoidal endothelial cells caused by ischemia/reperfusion and that conventional SOD had no such protective effect. Thus, O2- produced by ischemia/reperfusion apparently damages sinusoidal endothelial cells, and damage to hepatic parenchymal cells is secondary. Mannosylated SOD deserves further study for possible use in surgical resection of the liver and for liver transplantations.
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PMID:Mannosylated superoxide dismutase inhibits hepatic reperfusion injury in rats. 859 29

A review of 550 consecutively transplanted liver grafts stored in University of Wisconsin solution (UW) was performed during a 4-year period to ascertain whether graft function was impaired by flushing the aorta with Eurocollins (EC) rather than UW during the harvesting. The outcome of 255 liver grafts flushed with UW in both the aorta and portal vein (group UW/UW) was compared with 295 liver grafts flushed with EC through the aorta and UW through the portal vein (group ECUW). Liver grafts in both groups were flushed with 1 L of UW during the back table procedure and subsequently stored in UW at 4 degrees C before transport. Donor and recipient characteristics, cold and warm ischemia times, and methods of transplantation were similar in both groups, except that the recipient prothrombin time (PT) before liver transplantation (LT) was lower in the UW/UW group. There was no significant difference between the groups with peak transaminases aspartate aminotransferase (AST) and alanine aminotransferase, maximum value of serum bilirubin within 10 days following LT, incidence of primary nonfunction, need for retransplantation, and patient and graft survival at 1 month. Results were improved, however, in the EC/UW group in regard to PT after LT, operative bleeding and proportion of grafts with histologic lesions at the reperfusion biopsy (P<0.001). These better results in the EC/UW group were confirmed when grafts transplanted in urgent situations were excluded from analysis and by multivariate analysis assessing the effects of pretransplant PT and AST values of the recipients combined with the method of liver cooling with each of the aforementioned criteria. In conclusion, the method of using EC for the aortic flush during liver procurement reduces the amount of UW solution by 50% with improved graft function. This method seems justified in that it is less expensive while affording improved graft function.
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PMID:Beneficial effects of Eurocollins as aortic flush for the procurement of human livers. 860 71


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