Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xanthine dehydrogenase activity was determined in blood serum of rats in which diabetes had been induced by alloxan administration. The results show that there is no statistical significance in the difference found for normal and diabetic rats. Alloxan produced an inhibition in the enzyme activity in animals in which a carbon tetrachloride hepatotoxicity had been induced.
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PMID:Serum xanthine dehydrogenase of carbon tetrachloride-induced hepatotoxicity in alloxan-diabetic rats. 29 57

The in vitro potency of neopterin (NP) as an antioxidant and its in vivo activity to suppress alloxan-induced diabetes were investigated. The reduced form of neopterin, 5,6,7,8-tetrahydroneopterin (NPH-4), showed an extremely high superoxide anion radical scavenging activity in two assay systems, i.e. xanthine/xanthine oxidase- and macrophage/phorbol myristate acetate (PMA)-reaction systems. NPH-4 also inhibited the oxidation of linoleic acid about as effectively as uric acid. Furthermore, NPH-4 and NP effectively suppressed alloxan-induced mouse diabetes. These results suggest that pteridines play an important role as endogenous antioxidants.
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PMID:Neopterin as an endogenous antioxidant. 131 24

We propose new hypotheses for the mechanisms of streptozotocin (STZ) and alloxan inducing experimental diabetes in animals. STZ is transported into pancreatic beta cells through glucose transporter in the cell membranes and attacks mitochondria. Mitochondrial ATP generation is inhibited and the resulting high concentration of intracellular ADP causes its degradation providing hypoxanthine, a substrate of xanthine oxidase (XOD) whose activity is intrinsically very high in beta cells. Then, XOD-catalyzing reaction is proceeded as proved by increased formation of uric acid and O2- radicals are produced, but beta cells are inefficient to scavenge these radicals because of their extremely low activity of superoxide dismutase. On the other hand, STZ directly activates XOD and enhances O2- generation. Consequently, pancreatic beta cells are dually suffered from O2- radicals or probably hydroxyl radicals derived from the former when exposed to STZ. Allopurinol, an inhibitor of XOD, can protect animals from the diabetogenic effect of STZ. In pancreatic beta cells, alloxan anion radicals are generated from alloxan probably mediated by the action of microsomal cytochrome P-450 system. These radicals have long half-life and directly damage DNA in vitro. The widely accepted hypothesis that the cause of alloxan-induced diabetes is attributable to O2- radicals formed from alloxan is excluded, because alloxan itself shows a very potent scavenging effect to O2- radicals. Therefore alloxan anion radicals seem to be directly related to the incidence of diabetes by alloxan.
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PMID:[New hypotheses for the mechanisms of streptozotocin and alloxan inducing diabetes mellitus]. 148 45

Dupuytren's contracture is a deforming, fibrotic condition of the palmar fascia which has confounded clinicians and scientists since the early descriptions by Guillaume Dupuytren in 1831. It predominantly affects elderly, male caucasians, has a hereditary predisposition and has strong associations with diabetes, alcohol consumption, cigarette smoking and HIV infection. The major morphological features are an increase in fibroblasts, particularly around narrowed fibroblasts; a finding consistent with localised ischaemia. During ischaemia, adenosine triphosphate (ATP) is converted to hypoxanthine and xanthine, and endothelial xanthine dehydrogenase to xanthine oxidase (alcohol also mediates this change, a finding of particular relevance given the association of Dupuytren's contracture with alcohol intake). Xanthine oxidase catalyses the oxidation of hypoxanthine to xanthine and uric acid with the release of superoxide free radicals (O2-), hydrogen peroxide (H2O2) and hydroxyl radicals (OH.). These free radicals are highly reactive, with half-lives in the order of milliseconds and are toxic in high concentrations. A potential for free radical generation in Dupuytren's contracture was elicited by finding a sixfold increase in hypoxanthine concentrations in Dupuytren's contracture compared with control palmar fascia. In vitro studies affirmed the toxic effects of oxygen free radicals to Dupuytren's contracture fibroblasts, but also showed that, at lower concentrations (concentrations similar to those likely to occur in Dupuytren's contracture), free radicals had a stimulatory effect on fibroblast proliferation. Cultured fibroblasts were found to release their own O2-. These endogenously released free radicals were also found to be important in fibroblast proliferation. The collagen changes of Dupuytren's contracture were examined. The results established that fibroblast origin was unimportant, but that inhibition of type I collagen production at high fibroblast density accounted for the increase in type III/I collagen ratios observed by previous investigators. These biochemical and morphological observations throw new light on Dupuytren's contracture. They suggest that age, genetic and environmental factors may contribute to micro vessel narrowing with consequent localised ischaemia and free radical generation. Endothelial xanthine oxidase derived free radicals may both damage the surrounding stroma and stimulate fibroblasts to proliferate. Proliferating fibroblasts lay down and contract collagen in lines of stress.Progressive fibroblast proliferation and deposition of collagen is likely to encourage further microvessel narrowing with a positive feedback effect consistent with the progressive nature of the condition.
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PMID:An insight into Dupuytren's contracture. 161 55

The following species; superoxide (O2-.), hydrogen peroxide (H2O2), hydroxyl radical (.OH) and singlet oxygen (1O2), are generally called as reactive oxygen species (ROS). These species have been suggested to play important roles in various diseases caused by oxygen toxicity such as ischemia, carcinogenesis, inflammation, diabetes and aging. During the past two decades, considerable interests have been focused on chemical and biological research of ROS. We have also reported about the research results on ROS, which can be classified as following below; 1) chemical reactivities of O2-., 2) formation and toxicity of 1O2, 3) chemical reactivities of .OH, 4) enzyme mechanism of xanthine oxidase, 5) development of the compounds which induce the formation of O2-. and H2O2 in living cells and 6) development of superoxide dismutase mimics. These studies are reviewed from the standpoint of both chemical and biological interests.
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PMID:[Chemical and biochemical studies on reactivities, formations and toxicities of reactive oxygen species]. 164 54

Ultrastructural, immunohistochemical, and biochemical studies to date show that the fibroblast in Dupuytren's contracture is identical to palmar fascia fibroblasts in patients unaffected by Dupuytren's contracture, and to all other fibroblasts. The major difference relating to fibroblasts is that in Dupuytren's contracture there are more of them, and they are clustered around narrowed microvessels. It is probable that these two phenomena are linked because recent studies indicate a greater potential for ischemia-induced oxygen free radical generation in Dupuytren's contracture, and because oxygen free radicals in these concentrations can stimulate fibroblast proliferation. The major source of oxygen free radicals is likely to be from microvascular endothelial xanthine oxidase-catalyzed reactions. These observations also account for many of the epidemiologic associations of Dupuytren's contracture, because (1) age, race, and diabetes are associated with microvessel narrowing and (2) age, diabetes, alcohol consumption, HIV infection, cigarette smoking, and trauma are associated with increased free radical generation. Nonsteroidal anti-inflammatory drugs and allopurinol are two agents that decrease oxygen free radical release and may inhibit or prevent Dupuytren's contracture.
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PMID:The role of the fibroblast in Dupuytren's contracture. 176 89

Previous experiments on alloxan diabetogenicity suggest that alloxan increases the permeability of B-cell plasma membranes by generation of noxious free radicals. Whether the radicals are generated intra- or extracellularly has however been disputed. To test if extracellularly generated free radicals could decrease trypan blue exclusion of dispersed islet cells, a radical-generating solution of xanthine oxidase/hypoxanthine was employed. The solution increased dye uptake by cells in the cell suspension. Superoxide dismutase and catalase but not scavengers of hydroxyl radicals protected against the increase in dye uptake. Both L- and D-glucose protected the cells from injury. It is concluded that extracellularly generated free radicals induce damage to the plasma membrane of islet cells. The result strengthens the hypothesis of plasma membrane damage by extracellularly generated free radicals as the primary event in alloxan diabetogenicity and may provide a link for explanation of damage caused by islet inflammation in juvenile diabetes.
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PMID:Effect of extracellularly generated free radicals on the plasma membrane permeability of isolated pancreatic B-cells. 351 30

Recent observations indicate that OH . may be important in the microbicidal capacity of phagocytic cells, in prostaglandin metabolism, and as a mediator of inflammation. Although glucose is a weak hydroxyl scavenger, it occurs in high concentrations in biological systems. We therefore studied the capacity of glucose to scavenge OH . in biological systems known to generate this reactive oxygen species. Our experiments used a specific assay for the detection of OH .. We measured 14CO2 released during the oxidation of 14C-benzoic acid. We have previously demonstrated that benzoic acid is oxidized as a consequence of OH . in the following systems: the enzyme system xanthine-xanthine oxidase, zymosan-stimulated granulocytes, and arachidonic acid-stimulated platelets as a consequence of the lipoxygenase pathway. In all three systems the oxidation of benzoic acid was inversely proportional to the concentration of glucose in the assays. Also, platelets incubated with arachidonic acid and a high concentration of glucose increased HETE production, an effect predicted by the capacity of glucose to act as an OH . scavenger. Our results indicate that glucose acts as a scavenger of OH . in physiological concentrations and therefore may serve an antioxidant role in biological systems. In addition, the capacity of glucose to act as an OH . scavenger may explain some of the defects seen in patients with diabetes mellitus.
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PMID:Glucose: a role as a free radical scavenger in biological systems. 629 3

The in vitro antioxidative activity of benzylideneascorbate (SBA) and the in vivo effect on adriamycin (ADR)-induced cardiotoxicity in a mouse model were investigated. The radical-scavenging activity of SBA was assayed in terms of reduction of chemiluminescence induced by O2-, generated in xanthine/xanthine oxidase and macrophage/phorbol myristate acetate reaction systems. SBA showed a strong antioxidative activity (IC50 = 3 to 4 microM) in both assay systems, though its activity was weaker than that of ascorbic acid (Asc). In the assay of the antioxidative activity against auto-oxidation of linolenic acid, SBA was stable and retained its potency for a long period of time in comparison with Asc, 6-palmitoylascorbic acid (6-P-Asc) and cysteamine (CysNH2). Electron spin resonance examination indicated that SBA strongly scavenged both superoxide anion and hydroxy radical. The in vivo protective effect of SBA against ADR-induced cardiotoxicity, in which active oxygen radicals play a role, was examined. The serum creatine phosphokinase activity, a parameter of cardiotoxicity, was remarkably increased from the 3rd day until the 4th day after ADR treatment. This elevation was significantly suppressed by SBA treatment, whereas Asc, 6-P-Asc and CysNH2 were ineffective. SBA could have clinical potential for the treatment of diabetes and other disorders in which active oxygen species play a pathogenic role.
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PMID:Antioxidative activity of benzylideneascorbate and its effect on adriamycin-induced cardiotoxicity. 784 20

Low-density lipoproteins (LDL) oxidized by oxygen radicals are a potent atherogenic stimulus. Chemically modified LDL are internalized by macrophages via a specific cell surface receptor that was termed the scavenger receptor, and could induce foam cell transformation. Post-translational nonenzymatic glycosylation of low density lipoprotein (LDL) occurs in vivo in diabetic patients. Glycosylated LDL (glcLDL) is degraded by macrophages in part by the classic LDL-receptor and in part by the scavenger receptor. This latter mechanism may contribute to the formation of foam cells and acceleration of atherosclerosis in diabetes mellitus. Oxygen free radicals (ORs) could induce LDL peroxidation and subsequent formation of foam cells. Glycosylation may alter protein conformation. A free radical is any chemical species that has an unpaired electron. This property renders it highly chemically reactive. When a radical reacts with a non radical another free radical is generated. This characteristic enables radicals to trigger chain reactions. Oxygen radicals are: superoxide anion (.O2-), hydroxyl radical (.OH) and hydrogen peroxide (H2O2). Thus, the aim of this study was to investigate whether glcLDL are susceptible to peroxidative modification by ORs. GlcLDL was prepared incubating LDL with 40 mM glucose in sterile phosphate-buffer-EDTA 1 mM for 10 days at 37 degrees C. Control LDL (cLDL) was similarly incubated with buffer but without glucose. After this preparation both forms of LDL were oxidized by CuSO4 (15 microM for 20 hours at 37 degrees C) or by xanthine/xanthine oxidase (X:2 mM/XO: 100 mU for 20 hours at 37 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The peroxidation of human glycosylated low-density lipoproteins is mediated by the superoxide radical: the protective effects of superoxide dismutase]. 808 16


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