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)

In previous studies using isolated perfused rat livers, we have shown that reactive oxygen species are involved in hypoxic and ischaemic liver damage. Since albumin was shown to possess strong antioxidant properties we now investigated the capacity of albumin to prevent ischaemic and hypoxic damage in isolated perfused rat livers. Both, partial ischaemia and hypoxia/reoxygenation, resulted in marked hepatic injury as evidenced by an increased release of hepatic enzymes (GPT, LDH), by a strong decline of bile flow and by a decrease in hepatic GSH levels. With partial ischaemia, hepatic ATP depletion and calcium accumulation were also observed. Bovine serum albumin, added to the perfusate at concentrations of 0.1 or 1%, provided nearly complete protection against both types of liver injury. The same level of protection was also afforded by sulfhydryl-blocked and fatty acid-free bovine albumin preparations and by human albumin. In conclusion, the protective effect of albumin in our models of oxidative liver injury is neither due to the thiol moiety nor to the presence of oxidizable fatty acids in the albumin fraction. More likely, albumin provides protection by an unspecific binding of redox-active transition metal ions capable of catalyzing reactions which yield hydroxyl or hydroxyl-like radicals. Besides, unspecific sacrifice reactions of albumin with highly reactive oxygen species or other endogenous compounds may also be implicated.
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PMID:Protection by albumin against ischaemia- and hypoxia-induced hepatic injury. 787 Jun 99

Chronic acidosis evoked by a 7-day application of ammonium chloride in concentration of 2% increased the activity of glutamate decarboxylase (GAD) in renal homogenates of rats to approximately 160%. The enzyme activators, chlorides and adenosine triphosphate influenced in varying measures the GAD activity in renal homogenates of both controlled and acidotic animals. Whilst ATP was gradually loosing the activating effect, chlorides preserved it. The renal GAD is firmly bound on insoluble structures. The increase in GAD activity due to acidosis was accompanied by increasing permanence of this bind. After the substitution of ammonium chloride by drinking water, the return of the increased GAD activity to previous normal values lasted 7 days, whilst apparent normalization of the weight of experimental animals reoccurred on the first day. Subfractionation of the crude renal mitochondrial fraction by use of enzyme markers localized GAD in mitochondria. In renal homogenates the activities of GABA-transaminases were assessed. GABA-alpha-ketoglutarate transaminase was 5x more active than GABA-pyruvate transaminase. Acidosis resulted in augmentation of both transaminases--the first to 130%, the second to 160%. (Tab. 5, Fig. 3, Ref. 25.)
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PMID:[The effect of chronic acidosis on the activity of renal glutamate decarboxylase and GABA-transaminase]. 788 63

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

Alanine transport and the role of alanine amino-transferase in the synthesis and consumption of glutamate were investigated in the preparation of rat brain synaptosomes. Alanine was accumulated rapidly via both the high- and low-affinity uptake systems. The high-affinity transport was dependent on the sodium concentration gradient and membrane electrical potential, which suggests a cotransport with Na+. Rapid accumulation of the Na(+)-alanine complex by synaptosomes stimulated activity of the Na+/K+ pump and increased energy utilization; this, in turn, activated the ATP-producing pathways, glycolysis and oxidative phosphorylation. Accumulation of Na+ also caused a small depolarization of the plasma membrane, a rise in [Ca2+]i, and a release of glutamate. Intra-synaptosomal metabolism of alanine via alanine amino-transferase, as estimated from measurements of N fluxes from labeled precursors, was much slower than the rate of alanine uptake, even in the presence of added oxoacids. The velocity of [15N]alanine formation from [15N]glutamine was seven to eight times higher than the rate of [15N]-glutamate generation from [15N]alanine. It is concluded that (a) overloading of nerve endings with alanine could be deleterious to neuronal function because it increases release of glutamate; (b) the activity of synaptosomal alanine aminotransferase is much slower than that of glutaminase and hence unlikely to play a major role in maintaining [glutamate] during neuronal activity; and (c) alanine amino-transferase might serve as a source of glutamate during recovery from ischemia/hypoxia when the alanine concentration rises and that of glutamate falls.
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PMID:Cerebral alanine transport and alanine aminotransferase reaction: alanine as a source of neuronal glutamate. 790 47

Need of oxygen by the liver during hypothermic perfusion was evaluated using isolated perfusion model. Livers were perfused by a continuous perfusion system with oxygen saturated perfusate or nitrogen saturated perfusate, or simply stored for 12 hours at 5 degrees C. Quality of individual liver was assessed at one hour after normothermic reperfusion. Tissue edema was significant in all experimental groups, but the extent of which was much higher in nitrogen and simple cold storage groups. AST, ALT, LDH and PNP in the perfusate at the end of normothermic reperfusion were significantly higher in nitrogen and simple storage groups and those of oxygen group were similar to the control. Tissue adenine nucleotide and purine catabolite concentration in oxygen group was almost identical to the control at the end of hypothermic preservation, while ATP and energy charge in nitrogen and simple cold storage groups were significantly low. Conjugated dienes before and after reperfusion showed no difference in any groups, indicating no involvement of free radical injury on reperfusion in this asanguineous perfusion model. These results suggest that continuous supply of oxygen is necessary for liver preservation even though the temperature is lowered to inhibit cellular metabolism.
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PMID:Evaluation of oxygen necessity during hypothermic liver perfusion. 803 Dec 17

To identify factors predictive of early postoperative graft function, we analyzed 54 variables--including easily available clinical and laboratory data prospectively obtained from organ donors, transplant recipients and surgical procedures in 168 consecutive liver transplantations. Early postoperative graft function was classified into three groups according to a scoring system ranging from 3 to 9 based on peak serum ALT values, mean bile output and lowest prothrombin activity measured during the 72 hr after transplant: group 1 (score 3 to 4, good graft function; n = 73), group 2 (score 5 to 6, moderate dysfunction; n = 50) and group 3 (score, 7 to 9, severe dysfunction; n = 45). In univariate analyses, 8 of the 54 variables analyzed were statistically significant (p < 0.05) predictors of severe graft dysfunction: high serum sodium concentration and brain death caused by cranial trauma in organ donors, advanced age and low prothrombin activity in transplant recipients, prolonged total ischemia time and large transfusions of red blood cells, fresh frozen plasma and platelets during surgery. After introduction of these eight variables in a multivariate analysis, only four were found to independently predict early postoperative graft function: donor serum sodium concentration, total ischemia time, platelet transfusion during surgery and recipient prothrombin activity. In 52 liver transplantations, in which the predictive value of liver tissue adenine nucleotide concentration and several biochemical sensitive markers of donor nutritional status was also analyzed, only the ATP level in liver tissue obtained at the time of organ reperfusion was identified as an independent predictor of initial graft function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Predictive factors of early postoperative graft function in human liver transplantation. 807 15

Effects of 2% halothane, 1.5% sevoflurane, 1.5% enflurane, and 1.2% isoflurane on hepatic dysfunction were studied using rat hepatocytes incubated in media containing 95% or 5% O2. The effects of anesthetics on hepatic perfusion were eliminated by incubation of hepatocytes for 45 minutes with each combination of anesthetic and oxygen concentration. After incubation, viability of hepatocytes was assayed by the LDH latency test. Enzyme (GPT, GOT, LDH) activities, lactate concentration and pyruvate concentration in the incubation medium were measured. The concentrations of adenine nucleotides and inorganic phosphorous in the liver were determined. Anesthetics administered in 95% O2 did not produce significant decreases in viability and enzyme release compared to 95% O2 alone. Halothane, sevoflurane, and isoflurane administered in 5% O2 produced significant decreases in viability and enzyme releases compared to 95% O2 alone. In groups administered 95% O2 there was a significant relationship between viability and energy charge in hepatocytes (P < 0.01). In the 5% O2 groups, there were significant relationships between viability and ATP in hepatocytes (P < 0.01) or L/P ratio in incubation medium (P < 0.01). These results suggest that the combination of anesthetics and hypoxia produce hepatotoxicity. Destruction of energy status might be the cause of hepatotoxicity.
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PMID:[Hepatotoxicity of halogenated inhalational anesthetics studied in rats hepatocytes]. 818 7

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 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

Hamster sperm collected from the cauda epididymis were washed and the pellet diluted in a medium containing Triton x 100 (Sigma, Saint Louis, MO, USA) to dissolve the cell membrane and then reactivated with various concentrations of ATP (0-3 mM). Spermatozoal axonemes were initially immotile but the maximal percentage motility was obtained almost immediately following addition of 1 mM ATP. A stepwise increase in the concentration of ATP caused a 5-min delay in development of maximal reactivation and a change in the beating pattern as indicated by a decrease in the percentage of reactivating sperm. Under the same experimental condition GPT, UTP, CTP, and AMP failed to initiate the axonemal motility. In demembranated sperm reactivated by ADP, however, the beat frequency was lower compared with that reactivated by ATP. Pretreatment of the sperm with the mitochondrial phosphorylation blockers oligomycin and 2'4'-DNP (dinitrophenol) failed to inhibit the axonemal movement, although the presence of the dynein ATPase inhibitor, vanadate, was able to inhibit the reactivation. These results suggest that the exogenous ATP, but not the mitochondrial ATP, is responsible for axonemal motility.
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PMID:Specificity of ATP for the initiation of flagellar motility of hamster sperm. 827 42


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