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

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Query: EC:1.17.3.2 (xanthine oxidase)
8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ciclosporin A (CsA) is the first-choice immunosuppressant universally used in allotransplantation and autoimmune diseases. However, it has been demonstrated that this drug produces negative side effects in several organs and in particular in the lymphoid organs and in the kidney. It has been suggested that the CsA causes deleterious effects because it increases the oxygen free radical production. Here we wanted to test whether antioxidants protect the kidney parenchyma from the toxicity induced by CsA. We used methylene blue (MB), because it inhibits the formation of oxygen free radicals. The study was carried out in four groups of Wistar rats. Group I animals were intraperitoneally injected with MB (1 mg/kg/day) for 21 days; group II animals were subcutaneously injected with CsA (15 mg/kg/day) for 21 days; group III animals were treated with CsA combined with MB at the same doses and for the same periods as groups I and II, and group IV animals were injected subcutaneously with olive oil for 21 days as controls. The kidneys and the thymuses were subsequently removed and examined by conventional morphological staining (hematoxylin-eosin and Masson's trichrome) and enzymatic (NADPH-diaphorase, cytochrome, c oxidase, and superoxide anion production) and immunoenzymatic (inducible nitric oxide synthase--iNOS, endothelial nitric oxide synthase--eNOS) techniques. The thymuses were used to check the persistence of CsA-immunosuppressive effects during MB administration. Group I, III, and IV animals showed a normal kidney architecture and low levels of NADPH-diaphorase and of superoxide anion in all structures studied (proximal and distal tubules, glomeruli and the Henle loops). The cytochrome c oxidase showed a strong activity in proximal tubules, a moderate activity in distal tubules, and a weak activity in glomeruli and in the Henle loops. The expression of iNOS was weak in the proximal tubular epithelial cells and negative in the glomeruli, while eNOS was found to be moderately positive in the glomeruli and in the interstitial arteries, but not in the tubules and in the Henle loops. Degenerative changes with tubulointerstitial injury in the cortex of CsA-treated kidneys (group II) and increases of NADPH-diaphorase levels, iNOS activity, and superoxide staining were found in all structures. The expression of eNOS did not change in group I, III and IV animals. MB combined with CsA prevented the degenerative changes caused by CsA, preserving the structural, enzymatic, and immunoenzymatic integrity of the renal parenchyma. The mechanism by which MB exerts its protective action is not yet clear, but it seems to be due to its ability to inhibit xanthine oxidase and to quench nitric oxide production. Moreover, these data have been also supported by the following: (1) the superoxide anion levels were very high after CsA treatment and reduced after CsA-MB treatment, and (2) the iNOS levels increased in CsA-treated rats and showed normal levels after CsA-MB treatment. Moreover we demonstrated that MB administration did no compromise the CsA immunosuppressive effects, since the thymus showed a cytoarchitecture like that observed in CsA-treated rats.
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PMID:Does methylene blue protect the kidney tissues from damage induced by ciclosporin A treatment? 1159 98

Evidence is increasing in hypertensive models for an inflammatory reaction in the microcirculation with abnormal leukocyte counts and adhesion to the endothelium, enhanced arteriolar tone, and microvascular and tissue apoptosis. The spontaneous form of hypertension (SHR) is accompanied by a glucocorticoid-dependent increase in circulating leukocyte count with elevated levels of activation and at the same time depressed leukocyte-endothelial interaction and endothelial P-selectin function. The SHR exhibits immune suppression with lymphocyte apoptosis in the thymus. Generation of reactive oxygen species (ROS) in and around microvascular endothelial cells may regulate signal transduction pathways responsible for controlling gene expression and protein modification and thereby cause an elevation of vascular tone and, in excess, may form an injury mechanism for cells and tissue. A series of enzyme systems such as xanthine oxidase, reduced nicotinamide adenine dinucleotide phosphate/reduced nicotinamide adenine dinucleotide oxidase, and cytochrome P450 monooxygenases in conjunction with suppression of ROS scavengers seem to be involved in the oxidative stress responses in hypertension. The increase in ROS generation contributes to vascular remodeling, apoptosis, and proliferation of vascular smooth muscle, whereas gaseous monoxides such as nitric oxide and carbon monoxide have the ability to modulate elevated vascular tone and proliferative cell responses. Such biological actions of gases not only regulate activation of soluble guanylate cyclase but could also be attributable to inhibition of cytochrome P450 monooxygenases. We examine here the molecular basis of signal transduction by ROS, NO, and CO and functional alterations in their sensor molecules. An inflammatory reaction may underlie the pathogenesis of hypertension and its associated lesion formation and organ dysfunction.
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PMID:The inflammatory aspect of the microcirculation in hypertension: oxidative stress, leukocytes/endothelial interaction, apoptosis. 1215 3

In this study we compared the ability of extractable organic material from particulate and semivolatile fractions of gasoline emission to induce mutations in bacteria and form adducts with calf thymus (CT) DNA with corresponding data obtained from diesel exhaust. Exhaust particles from gasoline-powered passenger cars were collected on filters and semivolatile compounds were collected on polyurethane foam (PUF). The mutagenicity of the soluble organic fraction (SOF) was determined in Salmonella typhimurium strain TA98 and the DNA binding of aromatic compounds in the extracts was assessed by in vitro incubations with CT DNA and rat liver S9 (oxidative activation) or xanthine oxidase (reductive activation) followed by butanol-enhanced (32)P-postlabeling analysis. Semivolatile fractions of gasoline emission collected on PUF formed more CT DNA adducts than filter extracts under all reaction conditions, but showed a lower mutagenic potential than the corresponding particulate samples. This suggests that the capacity of PUF to collect exhaust particle-derived compounds and/or the efficiency of xanthine oxidase and enzymes in the rat liver S9 to activate these compounds to DNA binding metabolites was higher than expected. Gasoline extracts, benzo[a]pyrene and diesel particulate matter (SRM 1650) formed more S9-mediated DNA adducts as their dose increased, although a linear dose-response was not observed for the gasoline exhausts. Lower concentrations of gasoline and diesel extracts bound to DNA with greater efficiency than did 8-fold higher doses, suggesting complex interactions and/or an inhibition of S9 enzyme activities by the high doses. Diesel extracts formed higher levels of adducts than gasoline extracts, especially with the reductive activation system, suggesting that diesel extracts contain high levels of nitro-polycyclic aromatic hydrocarbons (nitro-PAHs). The higher direct-acting Salmonella mutagenicity in diesel extracts in comparison with gasoline extracts is consistent with diesel extracts containing higher concentrations of nitro-PAHs. The results of this study indicate that diesel extracts are more mutagenic and form more DNA adducts than gasoline extracts and that the effects of extract dose on DNA adduct formation are complex.
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PMID:Comparison of mutagenicity and calf thymus DNA adducts formed by the particulate and semivolatile fractions of vehicle exhausts. 1287 10

1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 +/- 2-126 +/- 3 mmHg; P < 0.001) and decreased thymus (P < 0.001) and bodyweights (P" < 0.01). Allopurinol decreased serum urate from 76 +/- 5 to 30 +/- 3 micromol/L (P < 0.001) in saline and from 84 +/- 13 to 28 +/- 2 micromol/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex-HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC-HT in the rat.
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PMID:Role of xanthine oxidase in dexamethasone-induced hypertension in rats. 1743 25

It has been demonstrated that administration of high concentrations of monosodium glutamate (MSG), induce oxidative stress in different organs, but not in thymus. In the present study we examined the role of oxidative stress in MSG-induced thymocyte apoptosis. MSG was administrated intraperitoneally (4 mg/g of body weight) for six consecutive days. Animals were sacrificed at 1st, 7th, and 15th day after last MSG dose. MSG administration to animals significantly increased apoptotic rate of thymocytes (P < 0.01), together with significant increase of malondialdehyde (MDA) level (P < 0.001) and xanthine oxidase (XO) activity (P < 0.01), in time dependent manner. Catalase activity, during examination period, was significantly decreased (0 < 0.01). Obtained results showed that MSG treatment induced oxidative stress in thymus, which may have an important role in thymocyte apoptosis induced by MSG.
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PMID:Effect of monosodium glutamate on oxidative stress and apoptosis in rat thymus. 1745 17

The DNA binding capacity of two nitro-substituted benzazolo[3,2-a]quinolinium chlorides (NBQs), NBQ-38 and NBQ-95, was evaluated upon their enzymatic reduction with hypoxanthine (HX)/xanthine oxidase (XO) under anaerobic conditions. In the presence of 2'-deoxyguanosine (2'-dG) or calf thymus DNA, covalent-addition products were monitored. Reactions of each NBQ with 2'-dG or DNA differed in the NBQ to HX molar ratio. Control reactions, one without HX/OX and another under aerobic conditions, were also analyzed. Adducts were isolated and characterized by high performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (ESI-MS). Authentic samples of the reduced forms of these NBQs, identified as ABQ-38 and ABQ-95, were synthesized as standards to monitor bioreduction processes. HPLC analysis showed that the yield of formation of an unknown product (possibly, 2'-dG-NHBQ-38 adduct) from the reaction of NBQ-38 with 2'-dG and DNA was proportional to the HX to NBQ-38 molar ratio. ESI-MS analysis of the DNA hydrolysates showed evidence of an adduct formed upon bioreduction of NBQ-38 by the ions detection at m/z 528.3 and 454.8, consistent with chemical structures of a 2'-dG-NHBQ-38 adduct and a fragment ion. DNA adducts were not observed with NBQ-95, although the corresponding bioreduction product ABQ-95 was detected by ESI-MS. This study provides mechanistic information of these bioreductively-activated pro-drugs with potential therapeutic applications.
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PMID:Comparison of the nucleic acid covalent binding capacity of two nitro-substituted benzazolo[3,2-a]quinolinium salts upon enzymatic reduction. 1746 86

Several dietary flavonoids such as quercetin, luteolin and genistein have been suggested to have cancer chemopreventive effects, although the mechanisms are not fully understood. In the present study, the effects of these flavonoids as antioxidants were investigated in the following systems: (1) production of hydrogen peroxide (H2O2) and superoxide anion (O2*-), (2) lipid peroxidation induced by FeCl2 in rat liver, and (3) formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) induced by either UV or Fenton reaction in calf thymus DNA. The results showed that quercetin and luteolin were equally potent in scavenging H2O2, with genistein having a moderate effect. Quercetin and luteolin had a potent inhibitory effect on O2*- generation by xanthine/xanthine oxidase while genistein had a moderate effect. Quercetin and luteolin were potent in inhibiting lipid peroxidation induced by FeCl2 in rat liver while genistein had a very weak inhibitory effect. All the test compounds had a potent quenching effect on 8-OHdG formation induced by UV light irradiation, with the order of effects being genistein > luteolin > quercetin. Of the test compounds, luteolin exhibited the most potent quenching effect on Fenton-induced 8-OHdG formation. The scavenging of oxygen free radicals, the inhibitory effect on lipid peroxidation and the quenching effect on 8-OHdG formation by quercetin, luteolin and genistein may, at least in part, be responsible for their anticarcinogenic effects.
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PMID:Dietary flavonoids, quercetin, luteolin and genistein, reduce oxidative DNA damage and lipid peroxidation and quench free radicals. 1837 28

Rarely repeated episodes of immobilization stress led to misbalance between pro oxidant and antioxidant systems. So in the brain, kidneys, spleen we observed elevation of oxidized proteins level. In contrast, in the thymus and bone marrow the protein carbonilation was attenuated. In the liver, oxidized protein level remained unchanged. Simultaneously the level of liver lipoperoxidation was increased. These shifts were accompanied with attenuation of catalase activity in the liver and elevation of xanthine oxidase activity in the spleen and erythrocytes.
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PMID:[Influence of repeated stress exposures with hypoxia intolerance on rats oxidized proteins and lipoperoxidation shifts]. 1919 86

The aim of the present study was to investigate the immunomodulatory effect and antioxidant activity of carboxymethylpachymaran on cyclophosphamide-induced immunosuppression in mice in vivo. The results showed that carboxymethylpachymaran could be used to overcome the cyclophosphamide-induced immunosuppression in mice. Moreover, it significantly increased the thymus and spleen indices, lysozyme, catalase and superoxidase dismutase activities, and total antioxidant capacity. In contrast, it decreased xanthine oxidase activity and malondialdehyde levels. The results indicated that carboxymethylpachymaran might play an important role in the prevention of oxidative damage in the immunological system.
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PMID:Inhibitory effect of carboxymethylpachymaran on cyclophosphamide-induced oxidative stress in mice. 2182 Oct 63

Ginsenoside Rg3 is one of the active ingredients isolated from Panax ginseng C.A. Meyer. Previous investigation demonstrated that Rg3 was stereospecific in promotion of the immune response. The present study was designed to evaluate Rg3 and its epimers, 20(R)-Rg3 and 20(S)-Rg3, for their effects on oxidative stress induced by cyclophosphamide (Cy) in mice. Forty-eight mice were randomly distributed into 6 groups and intraperitoneally administered saline solution, Cy, 20(R)-Rg3, 20(S)-Rg3, 20(R)-Rg3+Cy or 20(S)-Rg3+Cy. After that, the spleen, thymus and serum were collected to measure the indices of the organs and oxidative parameters. The results showed that Rg3 significantly inhibited Cy-induced oxidative stress in mice by increasing the indices of the spleen and thymus and total antioxidant capacity, elevating the activities of catalase, superoxidase dismutase and lysozyme as well as decreasing the activity of xanthine oxidase and the levels of malondialdehyde and nitric oxide. Rg3 was stereospecific in antioxidant activities as R form exhibited significantly higher antioxidant effects than S form. Therefore, R form should be used when Rg3 is considered to be used as an antioxidant agent.
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PMID:Stereospecific antioxidant effects of ginsenoside Rg3 on oxidative stress induced by cyclophosphamide in mice. 2231 Jan 72


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