Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated whether intraportal injection of 150 mg/kg N-acetylcysteine (NAC) into rats reduced hepatic ischemia-reperfusion injury after 48 hours of cold storage and 2 hours of reperfusion. The organ was isolated and perfused to evaluate liver function. The control group received an intraportal injection of 5% dextrose. NAC increased L-cysteine concentrations 15 minutes after injection (1.29 +/- 0.11 mumol/g vs. 2.68 +/- 0.4 mumol/g, P < .05). However, neither treatment modified glutathione liver concentrations relative to preinjection values. After 48 hours of cold storage and 2 hours of reperfusion, livers from NAC-treated rats produced larger amounts of bile than those in the control group (5.04 +/- 1.92 vs. 0.72 +/- 0.37 microL/g liver; P < .05), and showed a significant reduction in liver injury, as indicated by reduced release of lactate dehydrogenase (679.4 +/- 174.4 vs. 1891.3 +/- 268.3 IU/L/g; P < .01), aspartate transaminase (AST) (13.94 +/- 3.5 vs. 38.75 IU/L/g; P < .01), alanine transaminase ALT) (14.92 +/- 4.09 vs. 45.91 +/- 10.58 IU/L/g; P < .05), and acid phosphatase, a marker of Kupffer cell injury (344.4 +/- 89.6 vs. 927.3 +/- 150.8 IU/L/g; P < .01) in the perfusate. Reduced glutathione concentrations in the perfusate were similar in the two groups (805 +/- 69 vs. 798 +/- 252 nmol/L/g), whereas oxidized glutathione (GSSG) concentrations were higher in the control group (967 +/- 137 vs. 525 +/- 126 nmol/L/g; P < .05). Reduced glutathione (GSH) concentrations in liver tissue collected at the end of perfusion were significantly higher in the NAC group (7.3 +/- 0.9 vs. 4.1 +/- 1.0 mumol/g; P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effects of N-acetylcysteine on hypothermic ischemia-reperfusion injury of rat liver. 763 22

An accurate serologic measure of hepatic function would be clinically useful in selecting donors for liver transplantation. An experimental model that incorporates varying lengths of total hepatic warm ischemia with reperfusion injury was utilized to compare serologic parameters and mitochondrial performance of oxidative phosphorylation in predicting hepatocellular injury. Monoethylglycinexylidide (MEGX) formation following bolus intravenous lidocaine injection was found to be significantly decreased (P < 0.0001) at all periods of ischemia when compared to that in nonischemic controls. A serum MEGX level of < 50 micrograms/liter suggested severe hepatic damage. No correlation was found between MEGX level and liver viability as measured by animal survival. Serum transaminase (AST and ALT) levels demonstrated progressive, nonsignificant elevations with increasing length of ischemia (P = 0.0779 at the maximum ischemic time). Polarographic measurements of mitochondrial oxidative phosphorylation did not reveal a significant alteration in subcellular metabolism with prolonged ischemic time. These data highlight the comparative sensitivity of MEGX formation as an early quantitative measurement of hepatocellular injury during warm ischemia, although it was not predictive of organ viability.
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PMID:Monoethylglycinexylidide formation as an independent measure of warm hepatic ischemia and reperfusion injury. 764 94

This study was designed to investigate the changes in plasma and tissue endothelin-1/endothelin-2 (ET) after liver ischemia and to assess the protective effect of anti-ET 1/ET 2 monoclonal antibody (ET antibody) against ischemia-reperfusion injury. The ET levels in the liver tissue, hepatic venous blood of the ischemic and non-ischemic sides, and in the portal venous blood were measured before and after partial liver ischemia for 1 hour in the adult dog. The ET levels in the liver tissue and hepatic venous blood on the ischemic side increased slightly during ischemia and markedly after reperfusion, whereas those on the nonischemic side showed no significant increases. The ET levels in the portal venous blood peaked at 1 to 3 hours after ischemia, which was significantly higher than the levels in the hepatic venous blood on the ischemic side and which correlated with the portal venous pressure elevated because of the partial liver clamping. The administration of antibody (2 mg/kg, intravenous) before reperfusion resulted in a significant inhibition of the postreperfusion elevations of serum-glutamic-oxaloacetic transaminase (GOT), S-glutamic pyruvic transaminase (GPT), and the indocyanine green (ICG) dye retention rate. In conclusion, ET was produced both in the liver tissue exposed to ischemia and in the vascular endothelium of the portal bed exposed to portal congestion. The ET released from the vascular endothelium, including the liver and the portal bed, was found to be a possible factor of ischemia-reperfusion injury.
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PMID:Response of plasma and tissue endothelin-1 to liver ischemia and its implication in ischemia-reperfusion injury. 770 89

Ergot alkaloids possess some properties potentially beneficial in ischemia of organs. Therefore the effect of pretreatment by nicergoline and bromocriptine was established in ischemia-reperfusion injury of rat liver. PGE2 and verapamil were used as comparative agents. Hepatic ischemia (60 min) of anesthetized rats was induced by clamping of vessels supplying the median and left lateral lobe. Tested drugs were given i.v. 2 or 5 min prior to inducing ischemia. ALT and AST activities in serum two hours after the end of ischemia were used as markers of hepatocellular injury. Only PGE2 (0.1 mg.kg-1) pretreatment minimized the postischemic rise of both ALT and AST activities. Pretreatment with various doses of nicergoline (1 or 4 mg.kg-1), bromocriptine (1 or 4 mg.kg-1) and verapamil (0.9 or 4.5 mg.kg-1) did not influence significantly serum transaminases activities after ischemia. Bromocriptine (4 mg.kg-1) given together with PGE2 did not improve a protective effect against ischemia achieved by the administration of PGE2 (0.1 microgram.kg-1).
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PMID:The effect of pretreatment with prostaglandin E2 (PGE2), verapamil, nicergoline and bromocriptine on ischemia-reperfusion injury of rat liver in vivo. 776 87

Aiming at investigating biochemical markers of Primary Graft Nonfunction (PNF) in Orthotopic Liver Transplantation (OLT) an experimental work is made on 21 Large-White pigs randomly distributed in three groups of seven, and two additional groups of seven donors each. In Group I the supra and infrahepatic cava, the portal vein and the hepatic artery were clamped. After 30 minutes the caval and portal clamps were released and 30 minutes later the arterial clamp was also removed. In Group II (viable), OLT was performed. The Collins solution was used as preservation fluid, keeping the cold ischemia time under 2 hours. In Group III (Non-Viable), an OLT was carried out 24 hours of cold ischemia with Collins solution. Blood samples are taken in 8 different moments along the procedure to determinate the values of AST, ALT, LDH, FA, Bilirubin, Uric Acid, Cholesterol, Triglycerides, Urea, Creatinine, Glucose, Total Protein, Calcium, Phosphorus, CPK and Aldolase. The last 5 samples were drawn after reperfusion. In the Group III we found, in the samples drawn after reperfusion of the graft, significant increases in 5 of these parameters, AST, ALT LDH, Aldolase and Uric Acid. We consider that these 5 parameters may be of value in the early diagnosis of PNF of the graft, being the AST and ALT the most reliable, with the higher specificity for the same sensitivity.
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PMID:[Biochemical indicators of primary graft dysfunction in experimental orthotopic liver transplantation]. 776 81

Previously, pentoxifylline treatment of graft recipients was shown to protect against liver graft failure from storage/reperfusion injury after orthotopic rat liver transplantation. To determine whether pentoxifylline also protects against normothermic ischemia/reperfusion injury to liver, we induced lobar ischemia in rats followed by reflow and partial hepatectomy of the noninvolved liver. In rats receiving pentoxifylline 2 hr before surgery and then twice daily for 5 days, the 1-week survival rate more than doubled from 25% to 67% (P < 0.05). Liver enzymes (alanine transaminase, aspartate transaminase, and lactate dehydrogenase) in the serum and liver necrosis evaluated histologically were also significantly reduced in the pentoxifylline-treated rats (P < 0.01). Hepatic ischemia/reperfusion increased leukocyte infiltration into the lungs, and pentoxifylline tended to reduce this lung injury (P = 0.06). These results show that pentoxifylline treatment reduces hepatic injury and improves survival after normothermic ischemia and reperfusion.
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PMID:Protection by pentoxifylline against normothermic liver ischemia/reperfusion in rats. 777 68

Previous studies have demonstrated a role for both tumor necrosis factor (TNF) and reactive oxygen intermediates (ROI) in hepatic ischemia/reperfusion (I/R) injury. Biologically active TNF was present in liver homogenates in ischemic and nonischemic lobes after 2 h of ischemia but without reperfusion. Using an in situ liver perfusion model, we measured ROI, TNF, and hepatic enzymes in the effluent after 2 h of ischemia. Increased reduction of ferricytochrome C was observed in the hepatic effluent, indicative of the formation of ROI. Treatment of animals with TNF neutralizing antisera significantly reduced both ROI and aspartate aminotransferase (AST). Animals treated with superoxide dismutase (SOD), or SOD + catalase (CAT) had greater TNF in the hepatic effluent compared with I/R alone; however, SOD or SOD + CAT did not cause additional release of AST.SOD + CAT plus anti-TNF serum resulted in significant protection compared with SOD + CAT plus control serum. Reperfusion of ischemic liver with 4 mM H2O2 increased both TNF and AST. Optimal protection of hepatocellular injury from reperfusion injury is achieved with a combination of antioxidants and inhibition of TNF.
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PMID:Hepatic ischemia/reperfusion injury: importance of oxidant/tumor necrosis factor interactions. 781 Jun 59

Glutathione is important in cellular defense against oxidative stress. We postulated that administration of N-acetylcysteine (NAC), a glutathione precursor, might help maintain or replenish hepatic glutathione stores, thereby reducing reperfusion injury in liver grafts after warm ischemia. Eighteen pigs were subjected to 2 hr of warm hepatic ischemia and divided into a control group (group A, n = 6), a preischemia treatment group (group B, n = 6: NAC, 150 mg/kg, continuous i.v. infusion 1 hr before ischemia), and a postischemia treatment group (group C, n = 6: NAC, 150 mg/kg continuous i.v., begun 20 min before reperfusion and continued for 1 hr). At initiation of laparotomy, we measured hepatic levels of reduced glutathione (GSH), its oxidized form (GSSG), ATP, aspartate aminotransferase (AST), and lactate dehydrogenase (LDH). Before reperfusion, after 2 hr of warm ischemia, GSH, GSSG, and ATP were measured. One hour after reperfusion, we measured GSH, GSSG, ATP, AST, and LDH. Bile output was recorded every 10 min. Postoperfusion AST and LDH were significantly lower in both treatment groups than in controls. In group B, hepatic glutathione was maintained at significantly higher levels than in controls, even after ischemia (P < 0.05). In group C, although hepatic GSH levels fell until reperfusion, after administration of NAC, hepatic GSH reached the level of the preischemia treatment group. In both treatment groups, GSH 1 hr after reperfusion was significantly higher than in the controls (P < 0.01): regeneration of glutathione was seen in all 6 animals in group C, compared with 2/6 in group B and none in the control group. ATP recovery, bile output, and survival were all better in the treatment groups than in the control group. Pretreatment with NAC helps maintain hepatic glutathione during warm ischemia; given after ischemia, NAC is effective in replenishing depleted glutathione stores. Adjunctive use of NAC was associated with improved glutathione homeostasis, improved bile output and ATP regeneration, and increased survival.
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PMID:N-acetylcysteine ameliorates reperfusion injury after warm hepatic ischemia. 856 May 64

Since an occlusion of the vascular inflow to the liver is a useful technique in liver surgery, a relation between ischemia and regeneration in the liver is particularly important. The purpose of this study was to evaluate the effect of ischemic duration on liver regeneration after massive hepatectomy. Animals were subjected to segmental liver ischemia. After 30, 60, or 90 min, nonischemic liver lobes were resected (70% hepatectomy). Hepatectomy without prior liver ischemia was performed in the control group. On the 1st, 3rd, 5th, and 7th days following hepatectomy, a BrdU labeling index was calculated as a marker of liver regeneration. AST, ALT, and liver adeninenucleotides were also measured. Although 30 min of liver ischemia resulted in higher peak AST and ALT levels, liver regeneration and ATP levels were significantly higher than those in control animals. Ninety minutes of liver ischemia resulted in significantly lower liver regeneration and ATP levels compared with the other treatment paradigms. Liver regeneration and ATP levels were almost identical to those in control animals, in rats with 60 min of ischemia preceding hepatectomy. We conclude that livers regenerative capacities can tolerate significant ischemia and that relatively brief periods of ischemia can even accelerate liver regeneration.
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PMID:Duration of liver ischemia and hepatic regeneration after hepatectomy in rats. 788 25

Alteration of calcium metabolism in cells has been thought to be one of the main factors in ischemia-reperfusion injury. Serial changes in the tissue calcium content of the liver and the correlation between calcium level and liver injury were investigated. Experimental dogs were divided into two groups and subjected to hepatic ischemia of different duration: 60 min in Group A and 120 min in Group B, followed by reperfusion. Serum alanine aminotransferase, as an indicator of liver injury, was more elevated in Group B than in Group A. There was no change in hepatic calcium content during ischemia in either group. Immediately after reperfusion, there was no change in hepatic calcium level in Group A, whereas in Group B it was markedly elevated. The peak value occurred 30 min after reperfusion and gradually decreased thereafter, but did not return to pre-ischemic levels during the observation time. Plasma calcium concentrations in hepatic venous blood were markedly decreased in Group B 30 min and 60 min after reperfusion. These results suggest that calcium accumulation in the liver during the early reperfusion period may be one of the mediators of hepatic injury. To elucidate the mechanisms for elevation of calcium in hepatic tissue, serum malondialdehyde, a product of lipid peroxidation, was measured in hepatic venous blood. No elevation of serum malondialdehyde was observed in either group, indicating that the increases in calcium may not be due to oxidative stress. Serum mitochondrial aspartate aminotransferase and electron microscopic findings were used as indicators of mitochondrial injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in calcium content of the liver during hepatic ischemia-reperfusion in dogs. 789 Aug 88


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