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)

1. Poly (ADP-ribose) synthetase (PARS) is a nuclear enzyme activated by strand breaks in DNA which are caused by reactive oxygen species (ROS) and peroxynitrite. Excessive activation of PARS may contribute to the hepatocyte injury caused by ROS in vitro and inhibitors of PARS activity reduce the degree of reperfusion injury of the heart, skeletal muscle and brain in vivo. Here we compared the effects of various inhibitors of the activity of PARS with those of deferoxamine (an iron chelator which prevents the generation of hydroxyl radicals) and tiron (an intracellular scavenger of superoxide anion) on the degree of hepatic injury caused by ischaemia and reperfusion of the liver in the anaesthetized rat or rabbit. 2. In the rat, ischaemia (30 or 60 min) and reperfusion (120 min) of the liver resulted in significant increases in the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) indicating the development of liver injury. Intravenous administration of the PARS inhibitors 3-aminobenzamide (3-AB, 10 mg kg(-1) or 30 mg kg(-1)), 1,5-dihydroxyisoquinoline (ISO, 1 mg kg(-1)) or 4-amino-1,8-naphthalimide (4-AN, 3 mg kg(-1)) before reperfusion did not reduce the degree of liver injury caused by ischaemia-reperfusion. 3. In contrast to the PARS inhibitors, deferoxamine (40 mg kg(-1)) or tiron (300 mg kg(-1)) significantly attenuated the rise in the serum levels of AST and ALT caused by ischaemia-reperfusion of the liver of the rat. 4. In the rabbit, the degree of liver injury caused by ischaemia (60 min) and reperfusion (120 min) was also not affected by 3-AB (10 mg kg(-1)) or ISO (1 mg kg(-1)). 5. These results support the view that the generation of oxygen-derived free radicals mediates the liver injury associated with reperfusion of the ischaemic liver by mechanism(s) which are independent of the activation of PARS.
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PMID:Effects of inhibitors of the activity of poly (ADP-ribose) synthetase on the liver injury caused by ischaemia-reperfusion: a comparison with radical scavengers. 972 Jul 98

Objective. To determine the safety and efficacy of prophylaxis with palivizumab in reducing the incidence of hospitalization because of respiratory syncytial virus (RSV) infection in high-risk infants. Methods. A randomized, double-blind, placebo-controlled trial was conducted at 139 centers in the United States, the United Kingdom, and Canada. During the 1996 to 1997 RSV season, 1502 children with prematurity (</=35 weeks) or bronchopulmonary dysplasia (BPD) were randomized to receive 5 injections of either palivizumab (15 mg/kg) or an equivalent volume of placebo by intramuscular injection every 30 days. The primary endpoint was hospitalization with confirmed RSV infection. Children were followed for 150 days (30 days from the last injection). Those with hospitalization as a result of RSV infection were evaluated for total number of days in the hospital, total days with increased supplemental oxygen, total days with moderate or severe lower respiratory tract illness, and incidence and total days of intensive care and mechanical ventilation. The incidence of hospitalization for respiratory illness not caused by RSV and the incidence of otitis media were also evaluated. The placebo and palivizumab groups were balanced at entry for demographics and RSV risk factors. Ninety-nine percent of children in both groups completed the protocol and ~93% received all five scheduled injections. Results. Palivizumab prophylaxis resulted in a 55% reduction in hospitalization as a result of RSV (10.6% placebo vs 4.8% palivizumab). Children with prematurity but without BPD had a 78% reduction in RSV hospitalization (8.1% vs 1.8%); children with BPD had a 39% reduction (12.8% vs 7.9%). When gender, entry age, entry weight, BPD, and gestational age were included in a logistic regression model, the effect of prophylaxis with palivizumab remained statistically significant. The palivizumab group had proportionally fewer total RSV hospital days, fewer RSV hospital days with increased oxygen, fewer RSV hospital days with a moderate/severe lower respiratory tract illness, and a lower incidence of intensive care unit admission. Palivizumab was safe and well tolerated. No significant differences were observed in reported adverse events between the two groups. Few children discontinued injections for related adverse events (0.3%). Reactions at the site of injection were uncommon (1.8% placebo vs 2.7% palivizumab); the most frequent reaction was mild and transient erythema. Mild or moderate elevations of aspartate aminotransferase occurred in 1.6% of placebo recipients and 3.6% of palivizumab recipients; for alanine aminotransferase these percentages were 2.0% and 2.3%, respectively. Hepatic and renal adverse events related to the study drug were similar in the two groups. Conclusions. Monthly intramuscular administration of palivizumab is safe and effective for prevention of serious RSV illness in premature children and those with BPD.
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PMID:Palivizumab, a Humanized Respiratory Syncytial Virus Monoclonal Antibody, Reduces Hospitalization From Respiratory Syncytial Virus Infection in High-risk Infants. 972 60

The interaction between glycolysis, glutaminolysis and tumor growth in WAG/Fra rnu/rnu rats has been investigated. Small tumors are characterized by a low conversion of glucose to lactate whereas the conversion of glutamine to lactate is high. In medium sized tumors the flow of glucose to lactate as well as oxygen utilization are increased whereas glutamine and serine consumption are reduced. At this stage the tumor cells start with glutamate and alanine production. Large tumors are characterized by a low oxygen and glucose supply but a high glucose and oxygen utilization rate. The conversion of glucose to glycine, alanine, glutamate, glutamine, and proline reaches high values and the amino acids are released. Pyruvate kinase increases with tumor weight and is positively correlated with an increase in glucose and oxygen utilization. The shift from glutamate consumption to glutamate production is correlated with an increase in glutamate dehydrogenase and glutamate oxaloacetate transaminase activity.
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PMID:Pyruvate kinase and the interaction of amino acid and carbohydrate metabolism in solid tumors. 985 94

Blood samples from adult male and female Charles River Crl:CD (SD) BR rats were collected at weekly intervals for 4 wk to evaluate the effects of inhalation of an anesthetic dose of carbon dioxide (CO2) or of a carbon dioxide-oxygen mixture (CO2/O2) on hematology, coagulation, and serum biochemistry values. During the first 3 wk of the study, rats were assigned to 1 of 3 groups and were bled from the orbital sinus once weekly. Prior to the blood collection, rats in group 1 were exposed to room air only, rats in group 2 received CO2/O2 (approximately 66%:34% CO2:O2) by inhalation, and rats in group 3 received 100% CO2 by inhalation. In the rats exposed to CO2/O2 or CO2, leukocyte counts, lymphocyte counts, and glucose values were higher, and aspartate aminotransferase, creatine kinase, and calcium values were lower compared with those of rats exposed to room air only. Rats exposed to 100% CO2 had slightly (but statistically significant) lower mean corpuscular hemoglobin concentration when compared with rats exposed only to room air. During week 4, all rats were reassigned to 1 of 2 groups and were bled terminally via closed cardiac puncture following exposure to either CO2/O2 or CO2. Increased lymphocyte counts (males only) and glucose and chloride concentrations were noted for rats exposed to CO2/O2 compared with those exposed to CO2. These alterations reiterate the importance of comparing clinical pathology values to those of concurrent control groups that have experienced blood collection under identical conditions in order to avoid potential errors in the interpretation of data.
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PMID:Effects of carbon dioxide inhalation on hematology, coagulation, and serum clinical chemistry values in rats. 1020 85

The effect of various metabolic inhibitors on the rate of oxygen consumption by procyclic culture forms of Trypanosoma congolense utilizing proline as substrate was investigated. Cyanide inhibited the rate of oxygen consumption by 81.0 +/- 6.7%, malonate inhibited the rate by 51.6 +/- 1.6% and Antimycin A by 73.1 +/- 5.9%. A combination of cyanide and malonate inhibited the rate of oxygen consumption by 84.9 +/- 6.7% while a combination of antimycin A and malonate inhibited the rate by 81.6 +/- 7.6%. Rotenone had no effect on the rate of respiration except when the intact cells were first permeabilized by digitonin after which rotenone decreased the rate of respiration by 20-30%. Salicylhydroxamate (SHAM) did not have any effect on the rate of oxygen consumption. Enzymes involved in the catabolism of proline with high activities were: proline dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, fumarase, NADP-linked malic enzyme, alanine aminotransferase and malate dehydrogenase. Activities of 1-pyrroline-5 carboxylate dehydrogenase, glutamate dehydrogenase, aspartate aminotransferase and NAD-linked malic enzyme were detectable but lower. The end products of proline catabolism were alanine and glutamate. Unlike the case in Trypanosoma brucei brucei aspartate was not detected. Possible pathways of proline catabolism in procyclic culture forms of T. congolense and of electron transfer are proposed.
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PMID:Catabolism of proline by procyclic culture forms of Trypanosoma congolense. 1042 13

Lipid peroxidation due to oxygen free radicals (OFR) seems to play a major role in loss of liver graft viability after warm ischemia, preservation, and transplantation. N-acetylcysteine (NAC) is an antioxidant that has a direct effect on OFR, and is also a glutathione precursor, another antioxidant. This study was designed to evaluate the efficacy of NAC in preventing ischemia-reperfusion damage of liver grafts harvested from non-heart-beating donors. Liver transplantation was performed on pigs divided into five groups: group 1 (control group; n=5) received livers from heart-beating donors; livers were subjected to 30 min of warm ischemia in groups 2 (n=3, no NAC) and group 3 (n=3; NAC treatment); warm ischemia time lasted 60 min in groups 4 (n=4; no NAC) and 5 (n=5; NAC treatment). Studied parameters included graft survival for more than 3 days, aspartate aminotransferase plasma levels, liver histology, and hepatic total glutathione concentrations. Graft survival was 100% in groups 1, 2, and 3, 0% in group 4, and 20% in group 5. NAC treatment did not influence initial mean aspartate aminotransferase release which was greater in warm ischemic livers than in controls. NAC treatment had no effect on liver hepatic total glutathione after reperfusion of animals receiving warm ischemic grants. Finally, no effect on liver histology was observed with NAC treatment. Our study suggests that in liver transplantation from non-heart-beating donors, NAC has no effect in both graft viability and lipid peroxidation. The role of OFR in primary dysfunction of transplanted warm ischemic livers remains controversial.
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PMID:N-acetylcysteine in pig liver transplantation from non-heart-beating donors. 1045 34

In shock-wave-induced renal injury cavitation-generated free radicals play an important role. Using an in vitro model with Madin-Darby canine kidney (MDCK) cells, we investigated the influence of selenium, a free radical scavenger, in shock-wave-induced tubular cell injury. Suspensions of MDCK cells (33 x 10(6) cells/ml) were placed in small containers (volume 1.1 ml) for shock wave exposure. Two groups of 12 containers each were examined: (1) control (no medication), (2) selenium (0.4 microg/ml nutrient medium). Six containers in each group were exposed to shock waves (impulse rate 256, frequency 60 Hz, generator voltage 18 kV), while the other six containers in each group served as a control. After shock wave exposure, the concentration of cellular enzymes such as lactate dehydrogenase (LDH), N-acetyl-beta-glucosaminidase (NAG), glutamate oxaloacetate transaminase (GOT) and glutamate lactate dehydrogenase (GLDH) in the nutrient medium was examined. Following shock wave exposure there was a significant rise in LDH, NAG, GOT and GLDH concentrations. Selenium reduced this enzyme leakage significantly. Thus we conclude that selenium protects renal tubular cells against shock-wave-induced injury. Since selenium is an essential part of glutathione peroxidase, this effect seems to be mediated by a reduction in reactive oxygen species.
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PMID:Reduction of high-energy shock-wave-induced renal tubular injury by selenium. 1055 May 28

1 Poly (ADP-ribose) synthetase (PARS) is a nuclear enzyme activated by strand breaks in DNA, which are caused by reactive oxygen species (ROS). Here we investigate the effects of the PARS inhibitors 3-aminobenzamide (3-AB), nicotinamide and 1,5-dihydroxyisoquinoline (ISO) on the circulatory failure and the organ injury/dysfunction caused by haemorrhage and resuscitation in the anaesthetized rat. 2 Haemorrhage (sufficient to lower mean arterial blood pressure to 50 mmHg for 90 min) and subsequent resuscitation with shed blood resulted (within 4 h after resuscitation) in a delayed fall in blood pressure to 66+/-4 mmHg (control, n=13). This circulatory failure was not affected by administration (5 min prior to resuscitation) of 3-AB (10 mg kg-1 i.v., n=7), nicotinamide (10 mg kg-1 i.v., n=6) or ISO (3 mg kg-1 i.v., n=6). 3 Haemorrhage and resuscitation also resulted in rises in the serum levels of urea and creatinine. This renal dysfunction was attenuated by 3-AB and nicotinamide, but not by nicotinic acid (n=7), an inactive analogue of nicotinamide. Although ISO (n=6) also attenuated the renal dysfunction caused by haemorrhage and resuscitation, its vehicle (10% DMSO, n=4) had the same effect. 4 Haemorrhagic shock resulted in enhanced serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lipase, indicating the development of hepatocellular and pancreatic injury, respectively. Similarly, haemorrhagic shock also resulted in an increase in the serum levels of creatine kinase (CK) indicating the development of neuromuscular injury. This was attenuated by 3-AB and nicotinamide, but not by nicotinic acid. Although ISO also attenuated the liver, pancreatic and neuromuscular injury caused by haemorrhagic shock, its vehicle had the same effect. 5 Thus, activation of PARS contributes to the organ injury and dysfunction caused by haemorrhage and resuscitation in the rat.
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PMID:Effects of inhibitors of the activity of poly (ADP-ribose) synthetase on the organ injury and dysfunction caused by haemorrhagic shock. 1057 50

The continuous intragastric enteral feeding protocol in the rat was a major development in alcohol-induced liver injury (ALI) research. Much of what has been learned to date involves inhibitors or nutritional manipulations that may not be specific. Knockout technology avoids these potential problems. Therefore, we used long-term intragastric cannulation in mice to study early ALI. Reactive oxygen species are involved in mechanisms of early ALI; however, their key source remains unclear. Cytochrome P-450 (CYP)2E1 is induced predominantly in hepatocytes by ethanol and could be one source of reactive oxygen species leading to liver injury. We aimed to determine if CYP2E1 was involved in ALI by adapting the enteral alcohol (EA) feeding model to CYP2E1 knockout (-/-) mice. Female CYP2E1 wild-type (+/+) or -/- mice were given a high-fat liquid diet with either ethanol or isocaloric maltose-dextrin as control continuously for 4 wk. All mice gained weight steadily over 4 wk, and there were no significant differences between groups. There were also no differences in ethanol elimination rates between CYP2E1 +/+ and -/- mice after acute ethanol administration to naive mice or mice receiving EA for 4 wk. However, EA stimulated rates 1.4-fold in both groups. EA elevated serum aspartate aminotransferase levels threefold to similar levels over control in both CYP2E1 +/+ and -/- mice. Liver histology was normal in control groups. In contrast, mice given ethanol developed mild steatosis, slight inflammation, and necrosis; however, there were no differences between the CYP2E1 +/+ and -/- groups. Chronic EA induced other CYP families (CYP3A, CYP2A12, CYP1A, and CYP2B) to the same extent in CYP2E1 +/+ and -/- mice. Furthermore, POBN radical adducts were also similar in both groups. Data presented here are consistent with the hypothesis that oxidants from CYP2E1 play only a small role in mechanisms of early ALI in mice. Moreover, this new mouse model illustrates the utility of knockout technology in ALI research.
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PMID:CYP2E1 is not involved in early alcohol-induced liver injury. 1060 Aug 24

Active oxygen radical species are reported to cause organ damage. This study was designed to determine whether oxidative stress contributed to the initiation or progression of hepatic and splenic cell DNA damage induced by fumonisin B1 (FB1) in rats. Another aim was to investigate the protective effects of the antioxidants coenzyme Q10 (CoQ10), L-carnitine, vitamin E (alpha-tocopherol) and selenium against DNA damage in the liver and spleen of rats treated with FB1. Fasted rats were injected intravenously with a single dose of fumonisin B1 at 1.55 mg kg-1 body wt. into the tail vein. Treatment with FB1 led to splenic and hepatic DNA fragmentation in 85% of the test animals. DNA fragmentation was investigated as a critical event in toxic cell death by testing total Ca2+ in liver. FB1 administration caused total Ca2+ in liver to increase within 4 h (204% of control). Measurement of liver enzyme activities showed an increase in aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT). FB1 also markedly decreased splenic and hepatic glutathione (GSH) levels. Pretreatment with CoQ10 (30 mg CoQ10 kg-1 diet) together with L-carnitine (2.8 mg carnitine kg-1 diet), alpha-tocopherol (30 IU vitamin E kg-1 diet) and selenium (1 mg selenium as sodium selenite kg-1 diet), decreased DNA damage and the activities of Ca2+, ASAT and ALAT in the liver. On the other hand, the level of GSH was slightly increased. The CoQ10 alone did not significantly protect against toxic cell death and glutathione depletion caused by FB1. Oxidative damage caused by FB1 may be one of the underlining mechanisms of FB1-induced cell injury and DNA damage.
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PMID:Fumonisin B1-induced DNA damage in rat liver and spleen: effects of pretreatment with coenzyme Q10, L-carnitine, alpha-tocopherol and selenium. 1066 Sep 42


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