Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P17174 (aspartate aminotransferase)
14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of Tiron (4,5-dihydroxybenzene 1,3-disulfonic acid disodium salt) was examined in the treatment of beryllium-induced maternal and developmental toxicity in rats. Single administration of beryllium nitrate at a dose of 50 mg/kg (i.m.) on day 13 of gestation caused reductions in fetal and placental weights, the number of implantation sites and number of corpora lutea, as well as causing post-implantation loss, stunted growth, increase in the number of resorptions, and also a disturbed sex ratio. Maternal toxicity was demonstrated by reduction in body weight gain. Administration of beryllium also showed significant alteration in the hematological and biochemical indices of the mother as well as the fetus. Marked decreases were recorded in hemoglobin percentage, blood sugar levels, serum protein contents and serum alkaline phosphatase activity. By contrast, significant elevation was found in the activity of transaminases (aspartate aminotransferase and alanine aminotransferase). Tissue protein contents, glycogen contents, activities of alkaline phosphatase, adenosine triphosphatase and succinic dehydrogenase of kidney, lungs and uterus, and maternal and fetal liver all showed significantly decreased values after beryllium exposure, and remarkable elevation was observed in acid phosphatase, glucose-6-phosphatase and hepatic lipid peroxidation. These parameters were restored considerably with administration of 471 mg/kg i.m. Tiron from days 14 to 18 of gestation. Atomic absorption spectrophotometry also revealed a high concentration of beryllium in different organs of pregnant rats. Interestingly, a small amount of metal ion was also detected in the fetus and reduced accumulation of beryllium was noticed after Tiron treatment.
...
PMID:Protective effect of Tiron (4,5-dihydroxybenzene-1,3-disulfonic acid disodium salt) against beryllium-induced maternal and fetal toxicity in rats. 1218 11

An important biochemical feature of autotrophs, land plants and algae, is their incorporation of inorganic nitrogen, nitrate and ammonium, into the carbon skeleton. Nitrate and ammonium are converted into glutamine and glutamate to produce organic nitrogen compounds, for example proteins and nucleic acids. Ammonium is not only a preferred nitrogen source but also a key metabolite, situated at the junction between carbon metabolism and nitrogen assimilation, because nitrogen compounds can choose an alternative pathway according to the stages of their growth and environmental conditions. The enzymes involved in the reactions are nitrate reductase (EC 1.6.6.1-2), nitrite reductase (EC 1.7.7.1), glutamine synthetase (EC 6.3.1.2), glutamate synthase (EC 1.4.1.13-14, 1.4.7.1), glutamate dehydrogenase (EC 1.4.1.2-4), aspartate aminotransferase (EC 2.6.1.1), asparagine synthase (EC 6.3.5.4), and phosphoenolpyruvate carboxylase (EC 4.1.1.31). Many of these enzymes exist in multiple forms in different subcellular compartments within different organs and tissues, and play sometimes overlapping and sometimes distinctive roles. Here, we summarize the biochemical characteristics and the physiological roles of these enzymes. We also analyse the molecular evolution of glutamine synthetase, glutamate synthase and glutamate dehydrogenase, and discuss the evolutionary relationships of these three enzymes.
...
PMID:Nitrogen-assimilating enzymes in land plants and algae: phylogenic and physiological perspectives. 1220 56

Using a rat model of septic shock we studied the effects of Evodia rutaecarpa, a Chinese herbal medicine with antimicrobial and anti-inflammatory activity, on haemodynamic parameters, biochemical markers of organ function and nitric oxide (NO) production. Anaesthetized rats challenged with a high dosage of endotoxin (Escherichia coli lipopolysaccharide; LPS; 50 mg kg(-1), i.v.) for 6 h showed a severe decrease in mean arterial pressure. This was accompanied by delayed bradycardia, vascular hyporeactivity to phenylephrine and increase in plasma levels of lactate dehydrogenase, aspartate aminotransferase, bilirubin and creatinine, as well as NOx (NO2- plus NO3-). Pretreatment with ethanol extract of E. rutaecarpa (25, 50 and 100 mg kg(-1), i.v.), 1 h before LPS, dose-dependently prevented the circulation failure, vascular hyporeactivity to phenylephrine, prevented liver dysfunction and reduced the NOx over-production in plasma in endotoxaemic rats. A selective inducible NO-synthase (iNOS) inhibitor, aminoguanidine (15 mg kg(-1), i.v.), also effectively ameliorated the above pathophysiological phenomenon associated with endotoxaemia so that the normal condition was approached. Endotoxaemia for 6 h resulted in a significant increase in iNOS activity in the liver homogenate, which was attenuated significantly by E. rutaecarpa pretreatment. In summary, E. rutaecarpa, at the dosages used, exerted these beneficial effects probably through inhibition of iNOS activity and subsequent modulation of the release of NO. These significant results may offer E. rutaecarpa as a candidate for the treatment of this model of endotoxaemia.
...
PMID:Evodia rutaecarpa protects against circulation failure and organ dysfunction in endotoxaemic rats through modulating nitric oxide release. 1239 3

Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) seedlings were grown for 68 days in a growth chamber in nutrient solutions with ammonium, nitrate or ammonium nitrate as the nitrogen source. Among the nitrogen sources tested, whole-seedling biomass, relative growth rate (RGR), root and shoot elongation, and number of lateral roots, were greatest in seedlings grown with ammonium. In the absence of nitrogen, plant growth and formation of lateral roots were poor. Initially, glutamine synthetase, NAD-glutamate dehydrogenase and aspartate aminotransferase activities were high in young roots and shoots, but all three enzymatic activities decreased after one month of culture. In root apices, glutamine synthetase and aspartate aminotransferase activities were higher than NAD-glutamate dehydrogenase activity. Enzymatic activities were often higher in ammonium-fed seedlings than in seedings supplied with the other forms of nitrogen. Activities of all three enzymes were significantly reduced in seedlings grown in the absence of nitrogen. The beneficial effect of ammonium is discussed on the basis of its involvement in the assimilation pathways of Douglas-fir.
...
PMID:Effects of nitrogen source on growth and activity of nitrogen-assimilating enzymes in Douglas-fir seedlings. 1265 84

The relationship between acetaminophen (APAP) reactive metabolite formation, nitrotyrosine (NT) production, and cytokine elevation in APAP toxicity was investigated. Mice were dosed with 300 mg/kg of APAP and sacrificed at 1, 2, 4, 8, and 12 h. Serum aspartate aminotransferase (AST) was elevated by 4 h. The relative amount of NT correlated with toxicity and was localized in the necrotic cells. IL-1b was increased at 1 h, whereas IL-6, MIP-2, and MCP-1 were increased by 4-8 h. To determine the importance of reversible versus toxic events, N-acetylcysteine (NAC) was administered to mice either before APAP or 1, 2, or 4 h after APAP. The animals were sacrificed at 12 h. NAC treatment before APAP resulted in serum AST, serum nitrate plus nitrite as a measure of nitric oxide (NO) production, and hepatic cytokine levels that were similar to the controls. No APAP protein adducts or NT was present in these animals. In mice treated with NAC at 1 h, cytokines and serum AST were normal at 12 h, but APAP protein adducts were present in the hepatic centrilobular areas. No NT was present in these animals. In mice treated with NAC at 2 h and sacrificed at 12 h, serum AST was reduced by 80%. APAP adducts and NT were present in the centrilobular areas. Mice receiving NAC at 4 h had no protection from toxicity and serum nitrate plus nitrite. The NT and cytokine levels were similar to those of mice receiving APAP alone. The data suggest a relationship between metabolic events in APAP toxicity and the upregulation of NO, and IL-1b. IL-6, MIP-2, and MCP-1 appear to follow the toxicity. While it is a pre-requisite event, covalent binding per se does not appear to be a toxic event in the development of toxicity.
...
PMID:Effect of N-acetylcysteine on acetaminophen toxicity in mice: relationship to reactive nitrogen and cytokine formation. 1288 92

In order to investigate the effects of exposure to possible environmental pollutants such as Cd, Pb and Hg on haematological and serum biochemistry values, New Zealand White female rabbits were treated orally with distilled water solutions of CdSO4 x H2O, Pb(NO3)2 and HgCl2 (n = 4/treatment) in concentrations of 2.3, 4.1, and 30 mg/kg dry matter, respectively, for 28 days. The initial concentrations of Cd, Pb, and Hg in serum were significantly increased by the treatment. Exposure to Pb significantly decreased the red blood cell (RBC) count, haemoglobin (Hgb) concentration and the haematocrit (Hct) value. The Zn-protoporphyrin concentration did not change as a result of Pb exposure. Pb and Hg loading significantly increased the aspartate aminotransferase (AST) activity. Alanine aminotransferase (ALT) activity was also increased by both Hg and Cd exposure. Comparing the treated and the control rabbits, all the trace elements studied significantly reduced the activity of enzymes in the pancreatic tissues. The haematological results indicate that hyperchromic macrocytic anaemia developed in rabbits treated with Pb. The increased activities of both AST and ALT indicate pathophysiological changes of the liver parenchyma, which was verified by focal fatty infiltration seen histopathologically. Cd exposure could exert a toxic effect on the kidneys, although the slight tubulonephrosis developed would not possibly affect the renal function. The reduced activities of amylase, trypsin, protease and lipase induced by Cd, Pb and Hg suggest toxicity to the pancreas.
...
PMID:Effect of ingested heavy metals (Cd, Pb and Hg) on haematology and serum biochemistry in rabbits. 1451 58

Overdose of acetaminophen, a widely used analgesic drug, can result in severe hepatotoxicity and is often fatal. This study was undertaken to examine the effects of arabic gum (AG), which is commonly used in processed foods, on acetaminophen-induced hepatotoxicity in mice. Mice were given arabic gum orally (100 g l(-1)) 5 days before a hepatotoxic dose of acetaminophen (500 mg kg(-1)) intraperitoneally. Arabic gum administration dramatically reduced acetaminophen-induced hepatotoxicity as evidenced by reduced serum alanine (ALT) and aspartate aminotransferase (AST) activities. Acetaminophen-induced hepatic lipid peroxidation was reduced significantly by arabic gum pretreatment. The protection offered by arabic gum does not appear to be caused by a decrease in the formation of toxic acetaminophen metabolites, which consumes glutathione, because arabic gum did not alter acetaminophen-induced hepatic glutathione depletion. Acetaminophen increased nitric oxide synthesis as measured by serum nitrate plus nitrite at 4 and 6 h after administration and arabic gum pretreatment significantly reduced their formation. In conclusion, arabic gum is effective in protecting mice against acetaminophen-induced hepatotoxicity. This protection may involve the reduction of oxidative stress.
...
PMID:Protective effect of arabic gum against acetaminophen-induced hepatotoxicity in mice. 1452 29

Overproduction of nitric oxide (NO) in the liver has been implicated as an important event in endotoxin shock and in other models of hepatic inflammation and injury. The present study was undertaken to evaluate the effect of ONO-1714, a potent and specific inhibitor of inducible NO synthase (iNOS), on acetaminophen-induced hepatotoxicity in the rats. Oral administration of ONO-1714 dose-dependently inhibited NOx (NO2- and NO3-) accumulation in rat plasma after lipopolysaccharide (LPS) treatment. Intraperitoneal acetaminophen at 1 g/kg caused damage to the centrilobular regions of the liver and increase in serum alanine and aspartate transaminase (ALT and AST, respectively) levels accompanied by elevated plasma NOx levels after 24 h. Oral administration of ONO-1714 at 10 and 100 microg/kg dose-dependently reduced the acetaminophen-induced hepatic tissue damage and the increases in serum ALT and AST levels. ONO-1714 also blocked the increase in plasma NOx concentrations. These findings demonstrate that oral ONO-1714, an iNOS inhibitor, protects against acetaminophen-evoked hepatic inflammation/injury, strongly suggesting that NO produced by iNOS plays a key role in the pathogenesis of this drug-induced hepatotoxicity.
...
PMID:Effect of a potent iNOS inhibitor (ONO-1714) on acetaminophen-induced hepatotoxicity in the rat. 1465 71

The higher incidence of cardiotoxicity of doxorubicin (DOX)/paclitaxel (PTX) combination compared with DOX alone remains to be a major obstacle against effective chemotherapeutic treatment. We investigated the effect of sequence and time interval between administration of both drugs on the severity of cardiotoxicity of the combination. Male Wistar rats were divided into seven groups. DOX was administered intraperitoneally (i.p.) at a single dose of 5 mg x kg(-1) every other 2 days, 2 doses per week for a total cumulative dose of 20 mg x kg(-1). PTX was administered by an i.p. route at a dose of 20 mg x kg(-1) every other 2 days. Both drugs were injected either alone or sequentially in combination. In one case, DOX preceded PTX by 30 min and 24 h and in the other case, PTX preceded DOX by 30 min and 24 h. Cardiotoxicity was evaluated by both biochemical and histopathological examination, 48 h after the last DOX dose. DOX-induced cardiotoxicity was manifested by abnormal biochemical changes including marked increases in serum creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), glutathione peroxidase (GSH-Px), and aspartate aminotransferase (AST) activity levels. Myocardial tissue from DOX-treated rats showed significant increases in malondialdehyde (MDA) production and total nitrate/nitrite (NOx) levels, parallel with depletion of "endogenous antioxidant reserve," including GSH contents and GSH-Px activity level. PTX treatment produced significant changes in the biochemical parameters measured by a lower magnitude than those changes produced by DOX alone. Combination of both drugs resulted in aggravation of DOX-induced cardiotoxicity regardless the sequence and time interval between administration of either drug. Administration of PTX 30 min and 24 h after DOX treatment showed exaggeration of combination-induced cardiotoxicity compared with the reverse sequence. This exacerbation was manifested by much more pronounced changes in serum and cardiac tissue parameters measured. Histopathological examination of ventricles of rat's heart revealed that DOX treatment produced myo-cytolysis and myocardial necrosis. Administration of PTX following DOX treatment showed extensive myocardial necrosis compared with those rats treated with either DOX alone or the reverse sequence of administration. Moreover, rats treated with PTX 24 h after DOX treatment showed exaggeration of the combination-induced cardiotoxicity. In conclusion, PTX might synergistically aggravate DOX-induced cardiotoxicity. The effect might be much more pronounced with those rats treated with PTX 24 h after DOX treatment.
...
PMID:Cardiotoxicity of doxorubicin/paclitaxel combination in rats: effect of sequence and timing of administration. 1512 49

The role of poly(ADP-ribose) (PAR) glycohydrolase (PARG) in the pathophysiology of renal ischemia/reperfusion (I/R) injury is not known. Poly(ADP-ribosyl)ation is rapidly stimulated in cells after DNA damage caused by the generation of reactive oxygen and nitrogen species during I/R. Continuous or excessive activation of poly(ADP-ribose) polymerase-1 produces extended chains of ADP-ribose on nuclear proteins and results in a substantial depletion of intracellular NAD(+) and subsequently, ATP, leading to cellular dysfunction and, ultimately, cell death. The key enzyme involved in polymer turnover is PARG, which possesses mainly exoglycosidase activity but can remove olig(ADP-ribose) fragments via endoglycosidic cleavage. Thus, the aim of this study was to investigate whether the absence of PARG(110) reduced the renal dysfunction, injury, and inflammation caused by I/R of the mouse kidney. Here, the renal dysfunction and injury caused by I/R (bilateral renal artery occlusion [30 min] followed by reperfusion [24 h]) in mice lacking PARG(110), the major nuclear isoform of PARG, was investigated. The following markers of renal dysfunction and injury were measured: Plasma urea, creatinine, aspartate aminotransferase, and histology. The following markers of inflammation were also measured: Myeloperoxidase activity, malondialdehyde levels, and plasma nitrite/nitrate. The degree of renal injury and dysfunction caused by I/R was significantly reduced in PARG(110)-deficient mice when compared with their wild-type littermates, and there were no differences in any of the biochemical parameters measured between sham-operated PARG(110)(-/-) mice and sham-operated wild-type littermates. Thus, it is proposed that endogenous PARG(110) plays a pivotal role in the pathophysiology of I/R injury of the kidney.
...
PMID:Mice lacking the 110-kD isoform of poly(ADP-ribose) glycohydrolase are protected against renal ischemia/reperfusion injury. 1567 8


<< Previous 1 2 3 4 5 6 7 8 9 Next >>

---