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)

The role of reactive oxygen species in diabetes and its complications are well known. Two therapeutic agents commonly used in the treatment of diabetes are the sulfonylureas, gliclazide and glibenclamide. These drugs effectively reduce blood sugar in non-insulin dependent diabetes millitus by augmenting insulin release. Gliclazide is known to be a general free radical scavenger as demonstrated by inhibition of o-dianisidine photo-oxidation. In this study, the effects of gliclazide and glibenclamide on free radicals were examined in vitro, using electron spin resonance (ESR) spectroscopy. Superoxide radical (O2.-) generated from hypoxanthine-xanthine oxidase system, or hydroxyl radical (.OH) generated by the Fenton reaction, were analyzed as spin adducts of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). NO was generated from 1-hydroxy-2-oxo-3-(N-3-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7), and analyzed by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl (carboxy-PTI) produced from the reaction between 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) and NO. Gliclazide scavenged O2.-, .OH and NO in a dose-dependent manner whereas glibenclamide was without effect. These findings suggest that gliclazide is not only effective in reducing blood sugar but also may be beneficial by inhibition of lipid and protein denaturation, which leads to the development of diabetic complications.
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PMID:Gliclazide scavenges hydroxyl, superoxide and nitric oxide radicals: an ESR study. 922 46

Nitric oxide (NO) has cytotoxic effects but NO producing neurons are resistant to NO toxicity. These results suggest the presence of self-protecting factors for NO toxicity. Recently, 6R-tetrahydrobiopterin (6R-BH4), a cofactor for NO synthase (NOS), has been reported to degrade NO raising the possibility that 6R-BH4 acts as a self-protecting factor for NO toxicity. In PC12 cells which have NOS, three-day culture with sodium nitroprusside (SNP) or NOC-12, NO generators, at 10-100 microM increased nitrite and nitrate concentrations in the culture medium and induced death of PC12 cells. Coadministration of 6R-BH4 (10 or 30 microM) with SNP or NOC-12 prevented cell death with reduction of nitrite and nitrate in the medium. Inhibition of 6R-BH4 synthesis by 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor for GTP cyclohydrolase I, decreased cellular 6R-BH4 content and viable cell number. The inhibiting effects of DAHP were restored by exogenous 6R-BH4. NOS activity, as estimated by nitrite concentrations in the medium, was unchanged by DAHP. Hypoxanthine and xanthine oxidase, which produce superoxide, mimicked the cell-protecting effect of 6R-BH4 which is reported to generate superoxide during its autoxidation. These results suggest that 6R-BH4 acts as a self-protecting factor for NO toxicity with generation of superoxide in NO-producing neurons.
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PMID:Self-protection of PC12 cells by 6R-tetrahydrobiopterin from nitric oxide toxicity. 984 57

To test whether exogenous oxidants alter intracellular oxidant levels in skeletal muscle fibres, we exposed rat diaphragm to donors of nitric oxide (NOx), reactive oxygen species (ROS) or hyperoxia, and monitored intracellular oxidant levels using a fluorescent probe. Fibre bundles were dissected from the diaphragm and loaded with 2', 7'-dichlorodihydrofluorescein (DCFH); emissions were monitored using a fluorescence microscope. DCFH-loaded muscles were exposed to either a NOx donor (1 mM S-nitroso-N-acetyl penicillamine, SNAP; 1 mM sodium nitroprusside, SNP; 400 microM 1-hydroxy-2-oxo-3-(N-3-methyl-aminopropyl)-3-methyl-1-triazen, NOC-7), an ROS donor (100 microM hydrogen peroxide, H2O2; 100 microM tert-butyl hydroperoxide; 1 mM hypoxanthine plus 0.01 U mL-1 xanthine oxidase, HXXO) or a range of PO2s (25, 60 or 95% O2 oxygenating Krebs-Ringer solution) for 40 min; time-matched control bundles remained in Krebs-Ringer solution. Control muscles oxidized DCFH at a rate of 0.32 +/- 0.1 greyscale units min-1. SNAP (766%), SNP (1244%), NOC-7 (851%), H2O2 (543%), and HXXO (541%) increased DCFH oxidation from control levels. The increase in emissions caused by NOC-7 and SNP were blunted by the NOx scavenger haemoglobin (1 microM). DCFH oxidation by HXXO was unaffected by 1000 U mL-1 superoxide dismutase but was significantly decreased by 1000 U mL-1 catalase and 1 mM salicylate. PO2 had no effect on intracellular oxidant levels. Therefore, extracellular NOx and ROS can alter intracellular oxidant status in skeletal muscle fibres. These observations suggest that intrafibre oxidant levels could be the result of both intracellular and extracellular oxidant production.
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PMID:Exogenous reactive oxygen and nitric oxide alter intracellular oxidant status of skeletal muscle fibres. 1038 90

The antitumor potential of Cepharanthin was re-evaluated. Cepharanthin, a biscoclaurin alkaloid extracted from Stephania cepharantha Hayata, dose-dependently reduced the viable cell number of both normal and tumor cells, showing no tumor-specific cytotoxic action. Cepharanthin synergistically enhanced the cytotoxic activity of vitamin K3 and epigallocatechin gallate. Cepharanthin induced internucleosomal DNA fragmentation only in the human promyelocytic leukemic cell line HL-60. ESR spectroscopy showed that Cepharanthin effectively scavenged the superoxide anion (produced by hypoxanthine-xanthine oxidase reaction), the hydroxyl radical (produced by Fenton reaction) and nitric oxide (NO) (produced by NOC-7 in the presence of C-PTIO). The radical scavenging activity of Cepharanthin suggests its possible anticarcinogenic action. Cepharanthin dose-dependently inhibited the production of nitric oxide, but not that of tumor necrosis factor by lipopoysaccharide-stimulated mouse macrophage-like cells Raw 264.7. These data present a cautionary note that the cytotoxic activity of Cepharanthin is more prominent than its immunopotentiating activity.
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PMID:Re-evaluation of antitumor activity of Cepharanthin. 1201 81

Intraperitoneal administration of fermented pine seed shell extract (PSSE) (up to 2 g/kg) induced no apparent acute toxicity to mice. Pretreatment of mice with PSSE protected them from the lethality of Escherichia coli infection. PSSE showed a very weak cytotoxic activity against both normal and tumor cells and no anti-HIV activity, but stimulated the mouse macrophage-like Raw 264.7 cells to produce nitric oxide (NO) and citrulline. ESR spectroscopy showed that PSSE produced no detectable radicals, but effectively scavenged O2- (generated by the hypoxanthine-xanthine oxidase reaction), hydroxyl radical (generated by the Fenton reaction) and NO (generated by NOC-7). Comparison of PSSE with other natural products, such as polyphenols and vitamins, further confirmed the close association between radical intensity and radical scavenging activity, suggesting the bimodal action of natural products. Although the biological activities of PSSE were relatively lower than those of other natural products, the present study suggests the possible medicinal efficacy of PSSE.
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PMID:Diverse biological activities of fermented pine seed shell extract. 1216 38

A total of 14 poly-herbal formula extracts were compared for their biological activities both in vivo and in vitro. Pretreatment of mice with the extracts protected them from E. coli infection to various extents. Among the extracts, the HD-12 and DLH-3073 extracts showed the highest cytotoxicity against both HIV-infected and mock-infected MT4 cells, without induction of any apparent anti-HIV activity. The extracts showed significantly higher cytotoxic activity against five human tumor cell lines (HSC-2, HSC-3, HSG, MT-4, HL-60) than against three normal human cell lines (HGF, HPC, HPLF). Agarose gel electrophoresis demonstrated that the HD-12 and DLH-3073 extracts induced intemucleosomal DNA fragmentation in HL-60 cells. ESR spectroscopy showed that all the extracts produced radicals and this was paralleled by their ability to scavenge the superoxide anion (produced by hypoxanthine-xanthine oxidase reaction), the hydroxyl radical (produced by Fenton reaction) and nitric oxide (produced by NOC- 7) in the presence of radical trapping agents. Higher and lower concentrations of extracts enhanced or reduced respectively, the radical intensity of sodium ascorbate, suggesting their bimodal actions. The tumor specificity and antioxidant properties of the herb extracts further suggest their medicinal efficacy.
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PMID:Tumor-specificity and radical scavenging activity of poly-herbal formula. 1216 29

Among dental metals, copper showed the highest cytotoxicity against human oral squamous cell carcinoma and human submandibular gland carcinoma cells, followed by palladium-alloy, gold and silver. Normal human cells (gingival fibroblast, pulp cells, periodontal ligament fibroblast) were relatively resistant to these metals. The palladium-alloy failed to induce internucleosomal DNA fragmentation, a biochemical hallmark of apoptosis, in human promyelocytic leukemic HL-60 cells. The cytotoxic activity of the palladium-alloy was significantly reduced by a non-cytotoxic concentration of N-acetyl-L-cysteine, or more efficiently by sodium ascorbate. However, higher concentrations of sodium ascorbate enhanced the cytotoxic activity of palladium-alloy. ESR spectroscopy showed that the palladium-alloy enhanced the intensity of ascorbate radical, suggesting the possible interaction between metals and antioxidants. All metals, except copper, did not significantly affect the generation of superoxide anion (by hypoxanthine-xanthine oxidase reaction), hydroxyl radical (by Fenton reaction) and nitric oxide (from NOC-7 in the presence of C-PTIO). These data demonstrate for the first time that antioxidants modify the biological activity of dental metals.
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PMID:Interaction between dental metals and antioxidants, assessed by cytotoxicity assay and ESR spectroscopy. 1255 26

We investigated the radical scavenging activity of propolis by ESR spectroscopy using spin trapping method. In addition, we examined the influence of a diet of 2% propolis on mice under oxidative stress. At low concentrations, the methanolic extract of propolis exhibited strong scavenging activity in vitro towards both the superoxide anion radical, generated by the hypoxanthine-xanthine oxidase reaction, and the NO radical, generated from the mixture of NOC-7 (NO generator) and carboxy-PTIO (spin trapping agent). An inhibitory effect of propolis on lipid peroxidation in vivo was observed, as determined by measurement of thiobarbituric acid-reactive substances in mouse liver homogenate. The level of vitamin C in the brain of mice under oxidative stress significantly increased compared with control mice under atmosphere, which was not observed in the mice given 2% propolis. The level of alpha-tocopherol in the brain of mice given 2% propolis significantly increased compared with control mice under atmosphere, which was not observed in mice under oxidative stress. SOD activity in the brain and plasma of mice given 2% propolis significantly decreased under atmosphere and oxidative stress compared with control mice. These results suggest that propolis possesses potent antioxidant activity in vitro and in vivo.
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PMID:Free radical scavenging activity of propolis. 1268 27

Phenolcarboxylic acids (caffeic acid, p-coumaric acid, ferulic acid) and their dehydrogenation polymer (DHP) were compared for their ability to inhibit the nitric oxide (NO) production by lipopolysaccharide (LPS)-activated mouse macrophage-like cells Raw 264.7 and to scavenge superoxide (O2-) (generated by hypoxanthine and xanthine oxidase reaction), hydroxyl radical (generated by Fenton reaction) and NO radical (generated by NOC-7), using ESR spectroscopy in vitro. All phenolcarboxylic acids effectively inhibited the NO production by activated Raw 264.7 cells. Among them, caffeic acid showed the highest cytotoxic activity, radical intensity and O2- scavenging activity, but the least NO scavenging activity. Caffeic acid also inhibited the NO production most effectively. Polymers of caffeic acid (DHP-CA) and p-coumaric acid (DHP-pCA) showed higher cytotoxicity, radical intensity and radical scavenging activity and more efficiently inhibited the NO production, as compared with the corresponding monomers. DHP-CA showed higher radical generation and O2- scavenging activity than DHP-pCA. The potent O2- scavenging activity of caffeic acid was probably due to the chemical reaction of O2- to the cathecol groups. Caffeic acid, DHP-CA and DHP-pCA induced the cytotoxicity, possibly due to autogenerating radicals, because these compounds efficiently produced radicals under alkaline conditions. In summary, caffeic acid acted as a polyphenolics in phenylcarboxylic acids. A possible link between cytotoxicity and radical generation of phenylcarboxylic acids is proposed.
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PMID:Inhibition of NO production by activated macrophages by phenolcarboxylic acid monomers and polymers with radical scavenging activity. 1282 Mar 89

Hypoxia induces angiogenesis, partly through stabilization of hypoxia-inducible factor-1alpha (HIF-1alpha), leading to transcription of pro-angiogenic factors. Here we examined the regulation of HIF-1alpha by hypoxia and nitric oxide (NO) in explants of human cerebrovascular smooth muscle cells. Cells were treated with NO donors under normoxic or hypoxic (2% O2) conditions, followed by analysis of HIF-1alpha protein levels. Treatment with the NO donor sodium nitroprusside reduced levels of HIF-1alpha, whereas NO donors, NOC-18 and S-nitrosoglutathione, increased HIF-1alpha levels. SIN-1, which releases both NO and superoxide (O2*-), reduced HIF-1alpha levels, suggesting that inhibitory NO donors may elicit effects through peroxynitrite (ONOO*-). O2*- generation by xanthine/xanthine oxidase also reduced HIF-1alpha levels, confirming an inhibitory role for reactive oxygen species (ROS). Furthermore, superoxide dismutase increased HIF-1alpha levels, and the NO scavenger carboxy-PTIO reversed HIF-1alpha stabilization by NO donors. Effects on HIF-1alpha levels correlated with vascular endothelial growth factor transcription but did not affect HIF-1alpha transcription, as measured by RT-PCR and luciferase-reporter assays. The results indicate that HIF-1alpha is stabilized by agents that produce NO and reduce ROS but destabilized by agents that increase ROS, including O2*- and ONOO*-. Thus we propose that the effect of NO on HIF-1alpha signaling is critically dependent on the form of NO and the physiological environment of the responding cell.
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PMID:Nitric oxide and reactive oxygen species exert opposing effects on the stability of hypoxia-inducible factor-1alpha (HIF-1alpha) in explants of human pial arteries. 1465 4


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