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)

Nitric oxide (NO) plays an important role in a number of physiological processes in the airways, including host defense. Although the exact cellular and molecular source of the NO formation in airways is unknown, there is recent evidence that neuronal NO synthase (NOS1) contributes significantly to NO in the lower airways of cystic fibrosis (CF) patients. NOS1 protein has been shown to be expressed in nasal epithelium, suggesting an involvement of NOS1-derived NO in upper airway biology. We here hypothesized that nasal NO concentrations in CF patients are related to genotype variants in the NOS1 gene. Measurements of nasal NO concentration and pulmonary function were performed in 40 clinically stable CF patients. Genomic DNA from all patients was screened for an intronic AAT-repeat polymorphism in the NOS1 gene using polymerase chain reaction and simple sequence length polymorphism (SSLP) analysis. The allele size at that locus was significantly (P = 0.001) associated with upper airway NO. Mean (+/- SD) nasal NO concentrations were 40.5 +/- 5.2 ppb in CF patients (n = 12) with high repeat numbers (i.e., both alleles > or =12 repeats) and 72.6 +/- 7.4 ppb in patients (n = 28) with low repeat numbers (i.e., at least one allele <12 repeats). Furthermore, in the group of CF patients harboring NOS1 genotypes associated with low nasal NO, colonization of airways with P. aeruginosa was significantly more frequent than in patients with NOS1 genotypes associated high nasal NO concentrations (P = 0.0022). We conclude that (1) the variability in CF nasal NO levels are related to naturally occurring variants in the NOS1 gene, and (2) that nasal NOS1-derived NO affects the susceptibility of CF airways to infection with P. aeruginosa.
Nitric Oxide 2002 Mar
PMID:Nasal nitric oxide levels in cystic fibrosis patients are associated with a neuronal NO synthase (NOS1) gene polymorphism. 1189 Jul 49

Many studies in diverse models suggest that nitric oxide (NO) may be protective against liver injury due to ischaemia-reperfusion (IR). We evaluated, in an experimental in vivo model of rat liver partial ischaemia, the effects of pretreatment by an NO donor (spermineNONOate, 5mg/kg), and exogenous cGMP (8Br-cGMP, 16 mg/kg) or an endogenous cGMP producer (ANP, 10 microg/kg), to assess their beneficial effects. After 6h of reperfusion, 8Br-cGMP completely prevented the adverse effect of Nomega-nitro-L-arginine (10mg/kg) and 8Br-cGMP alone showed a protective action on both hepatocytes (AST, -25%, LDH, -55%) and endothelial cells (plasma hyaluronic acid (HA), -30%). ANP caused a marked decrease in AST and LDH activities only after 1h of reperfusion (AST, -30%, LDH, -40%). Pretreatment with spermineNONOate prevented hepatocyte injury after 1 and 6h of reperfusion (AST, -22%, LDH, -27%). However, neither spermineNONOate nor ANP had any protective effect on endothelial cell damage. These results confirm the beneficial effect of an NO donor and strongly suggest the implication of a cGMP pathway that does not involve a blockade of inflammatory cytokines production (IL-6 generation was unaffected by 8Br-cGMP pre-treatment). In our model, 8Br-cGMP showed a greater protective effect than ANP or spermineNONOate and so might be used to prevent hepatic injury after IR. Finally, we propose a schematic representation of the different routes for the actions of NO in protecting the liver against IR damage.
Nitric Oxide 2003 Sep
PMID:Hepatic cytoprotection by nitric oxide and the cGMP pathway after ischaemia-reperfusion in the rat. 1462 71

Mercury is a widespread metal in the environment and consequently large populations are currently exposed to low levels of mercury. Endotoxin, a component of the Gram-negative bacteria, promotes inflammatory responses. We recently reported that mercury modulates the production of nitric oxide and various inflammatory cytokines induced by endotoxin in a macrophage cell line (Nitric Oxide 2002, 7:67). The present study was designed to determine the impact of mercury on endotoxin-induced inflammatory cytokine expression and corresponding signal transduction in mouse liver. Male BALB/c mice were exposed continuously to 0, 0.3, 1.5, 7.5, or 37.5 ppm of mercury in drinking water for 14 days and at the end of the treatment period lipopolysaccharide (LPS, 0.5 mg/kg) was injected intraperitoneally 2 hr prior to euthanasia. The doses of mercury and LPS did not cause hepatotoxicity as indicated by unaltered circulating alanine aminotransferase and aspartate aminotransferase levels. Mercury decreased liver glutathione (GSH) and with LPS additively decreased GSH. Mercury activated p38 mitogen-activated protein kinase (MAPK) and additively increased LPS-induced p38 MAPK phosphorylation. In contrast, mercury alone had no effect on activation of extracellular signal-regulated kinase (ERK) but inhibited LPS-induced ERK activation. Mercury increased the expression of tumor necrosis factor alpha (TNFalpha) and further potentiated LPS-induced TNFalpha expression. Mercury did not affect LPS-induced interleukin (IL)-1beta expression but decreased LPS-induced IL-6 expression. Results indicated that low levels of mercury augment LPS-induced TNFalpha expression by altering GSH and p38 MAPK. Mercury modulates LPS-induced p38 and ERK activation and downstream TNFalpha and IL-6 expression in mouse liver.
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PMID:Mercury alters endotoxin-induced inflammatory cytokine expression in liver: differential roles of p38 and extracellular signal-regulated mitogen-activated protein kinases. 1580 65

Among the anesthetics influencing the nitric oxide (NO) pathway, ketamine is widely reported in the literature. We researched the variations in blood physiological parameters following ketamine/xylazine- or pentobarbital-induced anesthesia, with particular emphasis on plasmatic NO levels and oxidative stress-related factors. The effects of ketamine on hepatic blood flow during deep hypothermia were also examined. Adult male Sprague-Dawley rats were anesthetized intraperitoneally with ketamine/xylazine or with sodium pentobarbital. Animals underwent serial blood extraction to analyze acid-base balance and lactate levels in blood, as well as NO, MDA, SH groups, and AST levels in plasma samples. We demonstrated that ketamine leads to increased plasmatic NO levels, induces metabolic acidosis, and causes oxidative damage, though without reaching hepatic toxicity. When experimental hypothermia was induced, ketamine affected hepatic blood flow. Based on these results, we suggest that studies on physiological processes involving NO should exercise caution if anesthesia is induced by ketamine.
Nitric Oxide 2006 Aug
PMID:Nitric oxide induced by ketamine/xylazine anesthesia maintains hepatic blood flow during hypothermia. 1638 21

The goal of study was directed to investigate the effects of resveratrol (RES) pretreatment on the enhancing action of D-galactosamine (D-GalN; 800 mg/kg) on lipopolysaccharide (LPS; 0.5 microg/kg) inducing liver failure in rats. Liver function was assessed by determination of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-glutathione S-transferase (alpha GST) and bilirubin (BILI). Plasma NO(2)(-) was assessed by NO(2)(-)/NO(3)(-) colorimetric kit. The estimation of nonenzymatic and enzymatic antioxidants (glutathione and catalase) was performed in plasma and liver homogenate. Lipid peroxidation was evaluated by the thiobarbituric acid reacting substances (TBARS) and the conjugated dienes (CD). Morphological examinations using light and electron microscopy were performed. Observations related to pharmacological increases of inducible nitric oxide synthase (NOS-2)/nitric oxide (NO) and inducible heme oxygenase (HO-1) in fulminant hepatic failure and modulation by resveratrol were followed up by real-time reverse transcription PCR (RT-PCR) in liver tissue. In the present study we found that among the mechanisms responsible for the hepatoprotective effect of resveratrol in the LPS/D-GalN liver toxicity model are reduction in NO, downregulation of NOS-2, modification of oxidative stress parameters and modulation of HO-1 which led to overall improvement in hepatotoxic markers and morphology after the hepatic insult.
Nitric Oxide
PMID:Resveratrol attenuates lipopolysaccharide-induced hepatitis in D-galactosamine sensitized rats: role of nitric oxide synthase 2 and heme oxygenase-1. 1979 4

Iron is an essential element that participates in several metabolic activities of cells; however, excess iron is a major cause of iron-induced oxidative stress and several human diseases. Natural flavonoids, as rutin, are well-known antioxidants and could be efficient protective agents. Therefore, the present study was undertaken to evaluate the protective influence of rutin supplementation to improve rat antioxidant systems against IOL-induced hepatic oxidative stress. Sixty male albino rats were randomly divided to three equal groups. The first group, the control, the second group, iron overload group, the third group was used as iron overload+rutin group. Rats received six doses of ferric hydroxide polymaltose (100 mg kg(-1) b.wt.) as one dose every two days, by intraperitoneal injections (IP) and administrated rutin (50 mg kg(-1) b.wt.) as one daily oral dose until the sacrificed day. Blood samples for serum separation and liver tissue specimens were collected three times, after three, four and five weeks from the onset of the experiment. Serum iron profiles total iron, Total Iron Binding Capacity (TIBC), Unsaturated Iron Binding Capacity (UIBC), transferrin (Tf) and Transferrin Saturation% (TS%)}, ferritin, albumin, total Protein, total cholesterol, triacylglycerols levels and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were determined. Moreover, total iron in the liver, L-malondialdehyde (L-MDA), glutathione (GSH), Nitric Oxide (NO) and Total Nucleic Acid (TNA) levels and glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) activities were also determined. The obtained results revealed that, iron overload (IOL) resulted in significant increase in serum iron, TIBC, Tf, TS% and ferritin levels and AST and ALT activities and also increased liver iron, L-MDA and NO levels. Meanwhile, it decreased serum UIBC, total cholesterol, triacylglycerols, albumin, total protein and liver GSH, TNA levels and Gpx, CAT and SOD activities when compared with the control group. Rutin administration to iron-overloaded rats resulted in significant decrease in serum total iron, TIBC, Tf, TS%, ferritin levels and AST and ALT activities and liver total iron, L-MDA and NO levels with significant increases in serum UIBC, albumin, total protein and total cholesterol levels and in liver GSH, CAT and SOD activities compared with the IOL group. This study provides in vivo evidence that rutin administration can improve the antioxidant defense systems against IOL-induced hepatic oxidative stress in rats. This protective effect in liver of iron-loaded rats may be due to both antioxidant and metal chelation activities.
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PMID:Ameliorating role of rutin on oxidative stress induced by iron overload in hepatic tissue of rats. 2603 Oct 15