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 effect of warm ischemia and reperfusion injury in the regenerating rat liver after portal vein branch ligation (PBL) was examined by monitoring hepatic high energy phosphorous metabolism using in vivo Phosphorus-31 Magnetic Resonance Spectroscopy (31P-MRS). On 14 days after 70% occlusion of the portal vein, energy metabolism of non-occluded lobe of the liver was evaluated by measuring the ratio of beta-ATP to Pi obtained using 31P-MRS. During 30min-ischemia, beta-ATP/Pi dropped down similarly below the limit of observation in both of control and regenerating liver. However, after reperfusion, in the regenerating liver, the earlier and better recovery of beta-ATP/Pi was observed compared with the control. In the any examination of m-GOT, GPT, increase in enzyme level was apparently restrained in the PBL group. On the pathological examination, centrilobular necrosis and hepatocyte degeneration were remarkable in the normal liver, while in the regenerating liver, these changes were slight. In conclusion, these results suggest that reperfusion injury observed in the regenerating liver seems to be reduced compared with that in the normal liver. Functional and structural changes in the regenerating liver could be claimed as a course of this observation. However, to understand the mechanism, further study will be needed both in morphological and biochemical aspect.
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PMID:[Warm ischemia and reperfusion injury in the regenerating rat liver]. 827 66

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

Lipid peroxidation may play a major role in the loss of liver graft viability after prolonged cold ischemia and reperfusion injury. The lazaroid compound U74006F is a potent inhibitor of lipid peroxidation, and this study was designed to evaluate the efficacy of this compound in preventing cold ischemia-reperfusion damage in three different models: pig endothelial cells in culture, ex vivo isolated pig liver perfusion and orthotopic transplantation of syngeneic rat livers. The addition of U74006F to University of Wisconsin preservation solution significantly prolonged endothelial cell viability after 48 and 72 hr of cold ischemia and reoxygenation (p < 0.01). Donor pigs were injected with vehicle or U74006F (4.5 mg/kg) before liver harvest. After 24 hr of cold storage in University of Wisconsin solution, the livers were perfused with pig blood for 180 min in an isolation chamber. Measurements of liver function parameters, including AST, ALT, bile production, superoxide anion and phospholipase A2 release, were assessed every 60 min. Although bile production was similar in the U74006F-treated and control groups, significant decreases of AST and ALT levels (p < 0.01) in the perfusate of the livers from treated donors were observed. In addition, the U74006F group displayed significantly reduced release of superoxide anion and phospholipase A2 compared with these parameters in the untreated group (p < 0.05 and p < 0.01, respectively). In the last model, donor rats were treated with U74006F before harvest; the rat liver grafts were preserved in cold University of Wisconsin solution for 24 hr and then transplanted into recipient rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effect of the lazaroid U74006F in cold ischemia-reperfusion injury of the liver. 829 99

The number of clinical liver transplants that can be performed is limited by the availability of suitable donor organs. If it were possible to harvest and use livers after cardiac arrest, the supply could be improved. The mechanisms of damage in warm ischemia are not yet well understood and the consequences of transplanting a liver that is unable to provide immediate life-support are unacceptable. This study aims to identify areas for more detailed study in an attempt to improve the quality of livers harvested after significant warm ischemia, and to select acceptable organs for transplantation. Porcine livers were subjected to 75 min of warm ischemia and then perfused at 37 degrees C for 3 hr, during which period biochemical monitoring was carried out. At the end of the perfusion, histological and transmission electron microscopical studies were made. Large amounts of the intracellular enzymes ALT, AST, and LDH were released into the perfusate during the first 30 min of perfusion, but this--and the further amounts released during the subsequent 2.5 hr--was influenced by the composition of the perfusate. The inclusion of the substrates fructose and oleate, plus amino acids, substantially reduced this release and also improved the ability of the livers to metabolize ammonia. Oxygen free-radical scavengers had a significant, but smaller, beneficial effect. Electron microscopy confirmed the value of perfusion in improving cell morphology, and the additional value of including metabolic substrates. This study shows that hepatocellular structure and function can be improved by appropriate perfusion methods that also provide a simple means of monitoring some important functions. Both metabolic support and neutralization of oxygen free-radical action have a role to play in this approach to rendering ischemically injured livers acceptable for clinical use.
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PMID:The possibility of resuscitating livers after warm ischemic injury. 833 57

Between September 1988 and November 1991, 201 donor hepatectomies and transplantations were performed. Fifty-four livers (26.9%) were harvested by other teams and shipped for transplantation; 147 livers (73.1%) were procured by teams from our transplant center. Comparing the maximal postoperative serum-aminotransferases (s-AT), we evaluated the postischemic damage of shipped organs (AST 951 +/- 931 IU/l; ALT 820 +/- 666 IU/l) and nonshipped organs (AST 753 +/- 1256 IU/l; ALT 636 +/- 896 IU/l); this did not differ significantly. Donor-related factors, such as critical parameters (i.e., cardiac arrest, arterial hypotension, age over 50 years, or elevated preoperative s-AT), length of stay in the intensive care unit before harvesting, and cause of death showed similar patterns in both groups. The mean cold ischemia time in the group of shipped livers (12 h 10 min +/- 4 h 22 min) and in the nonshipped livers (10 h 6 min +/- 3 h 53 min) did not differ significantly. Five cases (2.5%) of a primary non-functioning graft presenting with significantly (P < 0.001) elevated s-AT (AST 4944 +/- 2280 IU/l; ALT 3186 +/- 1918 IU/l) necessitated an early retransplantation. One organ was shipped and four organs were nonshipped, thus corresponding to their portion of all grafts. These data indicate that the transplantation of shipped livers is a safe procedure procedure, provided that procurement is done by experienced centers.
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PMID:Transplantation of shipped donor livers. 834 65

The roles of neutrophil Mac-1 (CD11b/18) adhesion molecule, TNF-alpha and IFN-gamma in hepatic warm ischemia-reperfusion injury (IRI) were investigated with a newly established mouse model. Blood supply to the left lateral and the median lobe of the liver was interrupted with an atraumatic clip for 50 minutes. From 1 hour to 24 hours after reperfusion, TNF-alpha in the ischemic liver tissue was detected. IFN-gamma was not detected in ischemic liver tissue and blood. Pretreatment with anti-mouse Mac-1 monoclonal antibody (mAb) diminished the plasma GPT level, area of necrosis, and number of myeloperoxidase positive cells in ischemic liver lobe at 24 hours after reperfusion. Pretreatment with anti-mouse TNF-alpha or anti-mouse IFN-gamma mAb did not affected any parameters. From these results, Mac-1 was considered to play an important role in a hepatic warm IRI. However, TNF-alpha and IFN-gamma were not considered to play a pivotal role in the pathogenesis of the injury and in the regulation of the neutrophils adhesion via Mac-1.
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PMID:[Roles of Mac-1, endogenous TNF-alpha, and IFN-gamma in pathogenesis of hepatic warm ischemia-reperfusion injury]. 854 78

The protective effect of the calcium channel blocker nimodipine on liver ischemia and reperfusion was studied in the rat. The homeostasis of intracellular calcium ions seems to be a determinant factor in the cell injury that appears after ischemia and reperfusion. Nimodipine was used to downregulate the calcium levels in the cytosol of the ischemic cell, the hypothetical role of Ca2+ in the pathogenesis of ischemia and reperfusion injury. The experimental procedure consisted of the temporary interruption of blood flow to the left lateral and medial lobes of the rat liver and subsequent reperfusion after a period of 45 min of ischemia. Nimodipine (10 micrograms/kg body wt) was administered either before or after the onset of ischemia. The postischemic liver blood flow and liver oxyhemoglobin saturation were recorded using a He-Ne laser Doppler flowmeter and photometer, which showed, in the pretreated group, a recovery of reperfusion blood flow (58.1%) and liver reflectance (85.5%) significantly better (P < 0.01 and P < 0.001) than those in the respective untreated controls of flow (32.8%) and reflectance (70.5%). In the group that received nimodipine after ischemia, the recovery of the blood flow and the postreperfusion liver reflectance were not significantly better than those in the untreated control group. ALT levels (P < 0.05), galactose elimination capacity (P < 0.001), and histological studies also showed a protective effect of calcium antagonist nimodipine when administered before ischemia.
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PMID:Ischemia and reperfusion injury of the rat liver: the role of nimodipine. 859 15

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

The onset of warm ischemia and reperfusion injury in the liver was investigated in a canine model through changes in parenchymal markers [isozyme class V of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT)], endothelial markers [purine nucleoside phosphorylase (PNP) and hyaluronic acid clearance], and the liver metabolism (ketone body ratio) in warm ischemia induced by inflow occlusion using Pringle's maneuver and subsequent reperfusion. In this in vivo model, a PNP assay system and a model were designed so as to exclude the influence of wide localization of PNP possibly originating in erythrocytes or the intestine, and to discriminate between PNP of endothelial cells and that of parenchymal cells in the liver. After 45 min of warm ischemia, reperfusion resulted in damage only to endothelial cells, as seen by significant increase in PNP alone (3.6 +/- 0.1 U/liter at the end of warm ischemia to 6.8 +/- 0.5 U/liter at 5 min after reperfusion, P < 0.01) and significant decrease in hyaluronic acid clearance compared to the 30-min warm ischemia group in which no increase in either marker for parenchymal and endothelial cells was noted. By contrast, after 60 min of warm ischemia, reperfusion resulted in damage to parenchymal cells along with damage to endothelial cells, as seen by significant increases in LDH(V) and ALT (93 +/- 4 U/liter and 32 +/- 2 IU/liter at the end of warm ischemia to 239 +/- 17 U/liter and 165 +/- 27 IU/liter at 5 min after reperfusion, respectively), as well as a marked increase in PNP and deterioration of hyaluronic acid clearance compared to the 45-min warm ischemia group. Reperfusion after 120 min of warm ischemia did not show recovery of metabolic function of the liver as evaluated by hepatic mitochondrial redox state. It is suggested that a time lag occurs in the onset of injury between parenchymal cells and endothelial cells and that endothelial cells are temporally earlier in failing than parenchymal cells when the liver is exposed to short-term warm ischemia and subsequent reperfusion.
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PMID:Difference in onset of warm ischemia and reperfusion injury between parenchymal and endothelial cells of the liver. Evaluation by purine nucleoside phosphorylase and hyaluronic acid. 860 98

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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