Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.109 (AST)
 6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Indoxyl sulfate is a metabolite of tryptophan. Indole is synthesized in intestine from tryptophan by intestinal bacteria. The absorbed indole is converted to indoxyl sulfate through indoxyl in liver. Serum concentration of indoxyl sulfate is markedly increased as an inhibitor of drug-binding in uremic patients as compared with healthy subjects. Since indoxyl sulfate is bound to serum albumin, it cannot be removed efficiently by hemodialysis, and it tends to accumulate in uremic serum. To determine if oral sorbent, AST-120, could adsorb indole in intestine and then decrease serum concentration of indoxyl sulfate, it was administered to nephrectomized uremic rats. Serum concentration of indoxyl sulfate was markedly decreased in uremic rats fed with oral sorbent as compared with control uremic rats. However, serum concentrations of creatinine and urea nitrogen were not significantly decreased in the uremic rats fed with oral sorbent as compared with the control uremic rats. Serum concentration of tryptophan was not decreased but rather increased in the uremic rats fed with oral sorbent as compared with the control uremic rats. Concentration of indoxyl sulfate in bile of a uremic rat was much lower than that in the uremic serum, suggesting that the adsorption of indoxyl sulfate in intestine is not a major mechanism of decreasing the serum concentration of indoxyl sulfate. These results demonstrate that oral sorbent, AST-120, can decrease serum concentration of indoxyl sulfate in uremia due to adsorption of indole in intestine.
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PMID:[Effect of oral sorbent, AST-120, on serum concentration of indoxyl sulfate in uremic rats]. 212 Apr 92

The University of Wisconsin (UW) solution consists of a relatively complex mixture of agents. In this study we compared simpler preservation solutions, namely, histidine-tryptophan-ketoglutarate (HTK) and phosphate-buffered sucrose (PBS) with different compositions of UW solution in the isolated perfused rabbit liver model. Livers were stored cold for 24 and 48 h. After 24 h of preservation, the amount of bile produced in UW-preserved livers was significantly greater (P < 0.05) than that in HTK-preserved livers. Also, there was less LDH released into the perfusate in UW-preserved livers. There was more edema and lower K +/Na+rations in HTK-preserved livers than in UW-preserved livers (all data P < 0.05). After 48 h of preservation, the differences between livers preserved in UW or HTK solution were less noticeable than at 24 h and bile production was similar. LDH and AST release were greater in HTK-preserved livers than in UW livers, but these differences were not statistically significant. Preservation in PBS for 48 h was worse than in either UW or HTK solution. Substitution of polyethylene glycol (PEG) for hydroxyethyl starch (HES) in 48-h UW-preserved livers was not effective. We conclude that solutions simpler in composition than UW solution may be effective in kidney transplantation but do not appear suitable for successful liver preservation.
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PMID:Comparison of solutions for preservation of the rabbit liver as tested by isolated perfusion. 857 38

The activity of the enzymes involved in aminoacid metabolism (tyrosine aminotransferase, TAT, tryptophan pyrrolase TP, serine dehydratase, SD) with rapid response to glucocorticoids and enzymes requiring for activity increase repeated administration of corticosterone (alanine aminotransferase, ALT, aspartate aminotransferase, AST) in liver, the changes of lipolysis in adipose tissue and the plasma corticosterone levels were studied in rats subjected to space flight (F), in animals from synchron model experiments (SM, simulated conditions of space flight in laboratory) and in intact controls (C). The increase of plasma corticosterone concentration and of the activity of rapidly (TAT, TP, SD) and slowly activating enzymes (ALT, AST) was found in F group 6-10 hr after space flight (18.5 days on biosatellite COSMOS 1129). This suggested the presence of acute-stress (associated primarily with the landing) and chronic stress induced hypercorticosteronemia during the flight. After the short 6-day period of recovery the plasma corticosterone concentrations and the activities of liver enzymes returned to control levels. The exposition of animals to repeated immobilization stress showed higher response of corticosterone levels in flight rats as compared to intact controls. No changes in basal lipolysis were observed in flight rats in comparison to intact controls, however the stimulation of lipolysis by norepinephrine was lower in animals from F and SM groups. This lower response of lipolytic processes to norepinephrine was found in flight animals also after six days period of recovery. These results showed that there are important changes in the regulation of lipolytic processes in adipose tissue of rats after space flight and in the conditions of model experiments.
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PMID:Metabolic changes in the animals subjected to space flight. 1154 92

BACKGROUND: There are several reports that indicate a linkage between exposure to power frequency (50 - 60 Hz) magnetic fields with abnormalities in the early embryonic development of the chicken. The present study was designed to understand whether power frequency electromagnetic fields could act as an environmental insult and invoke any neurochemical or toxicological changes in developing chick embryo model. METHODS: Fertilized chicken eggs were subjected to continuous exposure to magnetic fields (50 Hz) of varying intensities (5, 50 or 100 microT) for a period of up to 15 days. The embryos were taken out of the eggs on day 5, day 10 and day 15. Neurochemical (norepinephrine and 5-hydroxytryptamine) and amino acid (tyrosine, glutamine and tryptophan) contents were measured, along with an assay of the enzyme glutamine synthetase in the brain. Preliminary toxicological investigations were carried out based on aminotransferases (AST and ALT) and lactate dehydrogenase activities in the whole embryo as well as in the liver. RESULTS: The study revealed that there was a significant increase (p < 0.01 and p < 0.001) in the level of norepinephrine accompanied by a significant decrease (p < 0.01 and p < 0.001) in the tyrosine content in the brain on day 15 following exposure to 5, 50 and 100 microT magnetic fields. There was a significant increase (p < 0.001) in glutamine synthetase activity resulting in the significantly enhanced (p < 0.001) level of glutamine in the brain on day 15 (for 100 microT only). The possible mechanisms for these alterations are discussed. Further, magnetic fields had no effect on the levels of tryptophan and 5-hydroxytryptamine in the brain. Similarly, there was no effect on the activity of either aminotransferases or lactate dehydrogenase in the whole embryo or liver due to magnetic field exposure. CONCLUSIONS: Based on these studies we conclude that magnetic field-induced changes in norepinephrine levels might help explain alterations in the circadian rhythm, observed during magnetic field stress. Also, the enhanced level of glutamine can act as a contributing factor for developmental abnormalities.
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PMID:Biological effects of power frequency magnetic fields: Neurochemical and toxicological changes in developing chick embryos. 1475 60

Transamination of tryptophan belongs to minor pathways of amino acid metabolism. The present paper describes conditions for application of dinitrophenylhydrazine method, originally prepared for alanine aminortansferase and aspartate aminotransferase assay, to the measurement of tryptophan transamination catalysed by any of the enzymes mentioned above. The method was tested using purified pig heart AST. While the free enzyme showed a characteristic absorption profile with the maxima at 360 and 430 nm, the course of transamination of tryptophan was confirmed by the measurement of UV-VIS spectral changes of the coenzyme in the active site of the enzyme in the presence of the amino acid substrate only, when tryptophan caused a shift of the peak from 360 nm to 330 nm due to a change of the pyridoxal form to the pyridoxamine form (= the first step of ping-pong transaminating reaction). A general limitation of dinitrophenylhydrazine method is the interference of hydrazones formed from the coenzyme pyridoxal-5'-phosphate and from the oxo- substrate 2-oxoglutarate, showing the absorption maxima at 492 nm and 388 nm, respectively with the hydrazones formed by the oxo- products (pyruvate and/or oxaloacetate in the case of ALT/AST, the absorption maxima at 443 nm in our measurements). In the case of tryptophan transamination, indolepyruvate as the oxo- product of a catalysed reaction forms dinitrophenylhydrazone, which has, besides a maximum at 435 nm, a distinct peak at 542 nm, convenient for the product concentration measurement. This is favourable for resolution from other (interfering) hydrazones. Suitable conditions for tryptophan transamination in tissue and enzyme preparations were found. Reaching optimal conditions for tryptophan transamination measurements in vitro is generally limited by low solubility of the amino acid in water solutions: With AST preparation, the velocity of catalysed reaction at 5-50 x 10(-3) M tryptophan concentration was of 1st order to the amino acid substrate. Km for tryptophan was found > or = 2 x 10(-1) M. Therefore the enzyme activity measurement at two different tryptophan concentrations is recommended for unknown samples. Tryptophan transamination by purified pig AST was compared with that catalysed by preparations obtained from mammalian tissues.
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PMID:Tryptophan metabolism via transamination. In vitro aminotransferase assay using dinitrophenylhydrazine method. 1520 68

Fibrosis plays a role in the pathogenesis of progressive chronic kidney disease (CKD). The inhibition of the renin-angiotensin system, which promotes fibrosis, has become the standard of care in the treatment of patients with CKD. A novel charcoal compound, AST-120, has been used for over a decade in Japan to prevent progression of CKD. It is thought that the oral administration of AST-120 blocks the intestinal absorption of tryptophan-derived indole. This prevents the hepatic conversion of indole to indoxyl sulfate (IS). IS has been shown to stimulate the production of profibrotic cytokines such as transforming growth factor-beta. AST-120 lowers IS in a dose dependent fashion and does not change the creatinine appearance rate in the urine. Enteric capsules containing Bifidobacterium longum have been shown to prevent progression of CKD in a preliminary study. These findings suggest that prospective clinical trials be undertaken to determine if these other potential methods of inhibiting fibrosis are useful in slowing progressive CKD.
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PMID:A nexus of progression of chronic kidney disease: charcoal, tryptophan and profibrotic cytokines. 1636 55

Histidine-tryptophan-ketoglutarate solution (HTK) and University of Wisconsin solution (UW) have been shown to have similar outcomes in cadaveric kidney, pancreas, and liver transplantation. Our institution changed from UW to HTK as the primary preservation solution for liver, kidney and pancreas transplantation. This study compares the perioperative and first year outcomes of liver transplantation using UW or HTK. Primary use of HTK began on May 1, 2003. We reviewed the records of all adult liver transplant recipients from July 1, 2002 to December 31, 2004. Recipients were compared based on organ preservation solution (UW n = 204, HTK n = 174). Outcomes included 1-, 6- and 12-month graft and patient survival and 1-, 7-, 14-, and 30-day liver function and serum creatinine. During the entire study period, the two groups were managed similarly in operative technique, immunosuppressive regimens, and donor liver criteria. Over 30 months, 378 adult patients underwent liver transplantation. There were no significant differences between UW and HTK in 1-, 6-, or 12-month graft or patient survival. The HTK group had a higher day 1 median AST, ALT, and total bilirubin, but the two groups were similar thereafter. An anticipated difference in infused volume between UW and HTK was demonstrated. In conclusion, to our knowledge, this is the first reported large case series from North America comparing HTK and UW in liver transplantation with 2- to 12-month follow-up. There were no significant differences between HTK and UW in this population when comparing 1 month graft function and first-year graft and patient survival.
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PMID:Comparison of histidine-tryptophan-ketoglutarate solution (HTK) and University of Wisconsin solution (UW) in adult liver transplantation. 1644 7

Fulminant hepatic failure (FHF) is a condition with a sudden onset of necrosis followed by degeneration of hepatocytes, without any previously established liver disease, generally occurring within hours or days. FHF is associated with a wide spectrum of neuropsychiatric alterations ranging from stupor to coma, culminating in death. In the present study FHF was induced in rats by the administration of thioacetamide (TAA). Oxidative stress is thought to play a prominent role in the pathophysiology of cerebral changes during FHF leading to the assumption that antioxidants might offer protection. Hence, in the present study the protective effect of C-Phycocyanin (C-PC), a natural antioxidant, was evaluated on TAA-induced tissue damage. C-Phycocyanin was administered intraperitoneally twice at 24 h interval (50 mg/kg body weight) along with the hepatotoxin TAA (300 mg/kg body weight). The animals were sacrificed 18 h after the second injection of TAA treatment and various biochemical parameters were analysed in liver, serum and brain tissues. These studies revealed significant prevention of TAA-induced liver damage by C-PC, as evidenced by a) increase in survival rate; b) the prevention of leakage of liver enzymes (AAT and AST) and ammonia into serum; c) increase in prothrombin time and d) liver histopathology. Ultrastructural studies of astrocytes of different regions of brain clearly showed a decrease in edema after C-PC treatment. TAA-induced histopathological lesions in different regions of the brain namely cerebral cortex, cerebellum and pons medulla were significantly reduced by the co-administration of C-PC with TAA. Further C-PC treatment resulted in a) decrease in the levels of tryptophan and markers of lipid peroxidation and b) elevation in the activity levels of catalase, glutathione peroxidase in different regions of brain. These studies reveal the potential of C-PC in ameliorating TAA-induced hepatic encephalopathy by improving antioxidant defenses.
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PMID:Co-administration of C-Phycocyanin ameliorates thioacetamide-induced hepatic encephalopathy in Wistar rats. 1716 76

University of Wisconsin (UW) solution has been recognized as the gold standard in liver preservation, but its limitations are becoming obvious, such as risk of biliary complications and its high cost. Alternatively, the effects of histidine-tryptophan-ketoglutarate (HTK), such as improved biliary protection and low cost, have been observed. This systematic review is conducted to compare the efficacy and safety of these 2 solutions. Databases from 1966 to June 2006 were searched. Randomized clinical trials (RCTs) and cohort studies comparing HTK and UW solutions for liver transplantation were included. Ten articles including 11 comparisons (1,200 patients) met the inclusion criteria, containing 2 RCTs and 9 cohort studies. No marked differences existed between the 2 groups in patient and graft survival rates, acute rejection, primary nonfunction, primary dysfunction, delayed graft function, and ALT and AST levels after transplantation. The only positive result was observed in the bile production after deceased donor liver transplantation (DDLT), which was statistically significantly higher in HTK group than that of UW group (95% confidence interval, 18.65-57.47; P=0.0001). Although the difference in biliary complications between the 2 groups did not reach statistical significance, HTK was thought to be more effective for biliary tract flush and prevention of biliary complications in some studies. There was no statistically significant difference of effects (except bile production) between HTK and UW. But trends were documented in some studies for the superiority of HTK in biliary tract flush, prevention of biliary complications, and cost saving. Adequately powered RCTs with longer follow-up periods are required to evaluate the long-term effect of these 2 solutions.
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PMID:Histidine-tryptophan-ketoglutarate solution vs. University of Wisconsin solution for liver transplantation: a systematic review. 1766 93

Indoxyl sulfate, a uremic toxin, is accumulated in the serum of chronic kidney disease (CKD) patients. A part of the dietary protein-derived tryptophan is metabolized into indole by tryptophanase in intestinal bacteria. Indole is absorbed into the blood from the intestine, and is metabolized to indoxyl sulfate in the liver. Indoxyl sulfate is normally excreted into urine. In CKD, however, an inadequate renal clearance of indoxyl sulfate leads to its elevated serum levels. The oral adsorbent AST-120 reduces the serum levels of indoxyl sulfate by adsorbing indole in the intestines and stimulating its excretion into feces. I have proposed a protein metabolite theory by which endogenous protein metabolites such as indoxyl sulfate play a significant role in the progression of CKD. A progressive decline in the glomerular filtration rate leads to increased serum levels of endogenous protein metabolites such as indoxyl sulfate, and to the adverse effects of their overload on the remnant nephrons. Indoxyl sulfate stimulates progressive both tubulointerstitial fibrosis and glomerular sclerosis by increasing the expression of transforming growth factor-beta1, a tissue inhibitor of metalloproteinase-1 and proalpha1 (I) collagen, leading to a further loss of nephrons. AST-120 delays the progression of CKD by removing serum indoxyl sulfate. Moreover, indoxyl sulfate induces oxidative stress in tubular cells, mesangial cells, vascular smooth muscle cells, endothelial cells and osteoblasts as well as stimulating aortic calcification in hypertensive rats, it is also involved in the progression of CKD, cardiovascular disease (CVD) and osteodystrophy. Thus, the removal of indoxyl sulfate by AST-120 ameliorates the progression of not only CKD, but also of CVD and osteodystrophy.
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PMID:Uremic toxicity of indoxyl sulfate. 2022 98


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