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)

We have studied the pathogenesis of murine cytomegalovirus (MCMV) pneumonitis in immunocompetent ICR mice and in mice treated with cyclophosphamide (CP). Intranasal infection of immunocompetent mice with MCMV resulted in transient and self-limited pulmonary lesions. When mice were given 200 mg/kg of CP one day before virus infection, transient splenic atrophy and subsequent splenic hypertrophy were induced, and the lesions in the lung were markedly augmented in their number and size although there was no significant enhancement of the virus growth. The augmentation coincided with the period of splenic hypertrophy. A marked increase in the number of pulmonary lesions was also induced in mice given 100 mg/kg of CP every 4 days following the initial dose of 200 mg/kg. In these mice, however, continuous splenic atrophy and augmented replication of MCMV in the lung were observed. When the activity of xanthine oxidase (XO) in lung tissue homogenates was measured, the activity was found to significantly increase after intranasal infection with MCMV irrespective of CP administration and there was a good correlation between the elevation of XO activity and the degree of pathological changes in the lung. In addition, we found that the administration of allopurinol, a specific inhibitor of XO and superoxide dismutase, a superoxide radical scavenger, reduced the number of the pulmonary lesions. These results suggest that superoxide radicals are involved in the pathogenesis of MCMV-associated pneumonitis in ICR mice.
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PMID:Pathogenesis of cytomegalovirus-associated pneumonitis in ICR mice: possible involvement of superoxide radicals. 133 50

Xanthine oxidase and purines have recently been detected in the circulation during acute viral infection and following hepatotoxicity and shock. Reactions of xanthine oxidase-generated oxidants with human plasma or bovine serum albumin (BSA) and egg phosphatidylcholine (PC) liposomes have been studied by measuring protein sulfhydryl oxidation and two markers of free radical-mediated lipid peroxidation, thiobarbituric acid reactive substances (TBARS) and conjugated dienes. Plasma incubated with 5 mU/ml xanthine oxidase (XO) and 0.5 mM hypoxanthine (Hx) for 2 h at 37 degrees C had 25-53% oxidation of sulfhydryl groups, with greater than 80% of the oxidation occurring during the first 20 min of the reaction. Concentrations of BSA similar to those present in serum, when exposed to XO/Hx-mediated oxidative stress, showed an even greater decrease in sulfhydryl concentration than that of plasma. No significant increase in plasma TBARS and conjugated dienes was observed during the 2-h incubation period in the presence of XO. Egg PC liposomes, suspended to a plasma phospholipid-equivalent concentration, showed a minor increase in TBARS and conjugated dienes under similar XO/Hx incubation conditions. In the presence of 0.23 mM BSA, lipid peroxidation was completely inhibited. A similar inhibition of lipid peroxidation was induced by cysteine but not by uric acid. Electrophoretic and arsenite-mediated sulfur reduction analysis revealed that BSA was oxidized beyond the disulfide form, with sulfenic acid formed during the initial period of oxidation. Protein sulfhydryls served as sacrificial antioxidants, preventing plasma lipid peroxidation, as well as being targets for oxidative damage. Plasma protein thiol oxidation was determined to be a more sensitive and specific indication of oxidant stress to the vascular compartment than assessment of lipid oxidation byproducts.
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PMID:Reaction of xanthine oxidase-derived oxidants with lipid and protein of human plasma. 189 41

We evaluated various biochemical parameters in influenza virus-infected mice and focused on adenosine catabolism in the supernatant of bronchoalveolar lavage fluid (s-BALF), lung tissue, and serum (plasma). The activities of adenosine deaminase (ADA) and xanthine oxidase (XO), which generates O2-, were elevated in the s-BALF, lung tissue homogenate, and serum (plasma). The elevations were most remarkable in s-BALF and in lung tissue: We found a 170-fold increase in ADA activity and a 400-fold increase in XO activity as measured per volume of alveolar lavage fluid. The ratio of activity of XO to activity of xanthine dehydrogenase in s-BALF increased from 0.15 +/- 0.05 (control; no infection) to 1.06 +/- 0.13 on day 6 after viral infection. Increased levels of various adenosine catabolites (i.e., inosine, hypoxanthine, xanthine, and uric acid) in serum and s-BALF were confirmed. We also identified O2- generation from XO in s-BALF obtained on days 6 and 8 after infection, and the generation of O2- was enhanced remarkably in the presence of adenosine. Lastly, treatment with allopurinol (an inhibitor of XO) and with chemically modified superoxide dismutase (a scavenger of O2-) improved the survival rate of influenza virus-infected mice. These results indicate that generation of oxygen-free radicals by XO, coupled with catabolic supply of hypoxanthine from adenosine catabolism, is a pathogenic principle in influenza virus infection in mice and that a therapeutic approach by elimination of oxygen radicals thus seems possible.
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PMID:Dependence on O2- generation by xanthine oxidase of pathogenesis of influenza virus infection in mice. 215 24

The pathogenicity of influenza virus infection in the mice involves, at least in part, overreaction of the immune responses of the host rather than a direct effect of virus multiplication. Xanthine oxidase, which is responsible for the generation of oxygen free radicals, was elevated in serum and lung tissue of mice infected with influenza virus. To test the theory that oxygen-free radicals are involved in pathogenesis, free radicals were removed by injecting superoxide dismutase (SOD), a specific superoxide radical scavenger, which was conjugated with a pyran copolymer. The conjugate protected mice against a potentially lethal influenza virus infection if administered 5 to 8 days after infection. These findings indicate that oxygen radicals are important in the pathogenesis of influenza virus infection, and that a polymer-conjugated SOD has therapeutic potential for this virus infection and other diseases associated with free radicals.
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PMID:Oxygen radicals in influenza-induced pathogenesis and treatment with pyran polymer-conjugated SOD. 254 70

An assay for human plasma xanthine oxidase activity was developed with pterin as the substrate and the separation of product (isoxanthopterin) by high-performance liquid chromatography with a fluorescence detector. The reaction mixture consists of 60 microliters of plasma and 240 microliters of 0.2 M Tris-HCl buffer (pH 9.0) containing 113 microM pterin. With this assay, the activity of plasma xanthine oxidase could be easily determined despite its low activity. As a result, it could be demonstrated that the intravenous administration of heparin or the oral administration of ethanol did not increase plasma xanthine oxidase activity in normal subjects, and also that plasma xanthine oxidase activity was higher in patients with hepatitis C virus infection than in healthy subjects or patients with gout. In addition, a single patient with von Gierke's disease showed a marked increase in the plasma activity of this enzyme, relative to that apparent in normal subjects.
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PMID:Determination of human plasma xanthine oxidase activity by high-performance liquid chromatography. 881 53

Reactive oxygen and nitrogen metabolites play a complex role in many diseases and in metabolic regulation. Because viruses replicate in living cells, such metabolites influence the growth of viruses in addition to serving as a host defense mechanism. Low levels of reactive oxygen species (ROS) play a role in mitogenic activation, and the early phase of lytic and nonlytic virus infection indeed resembles that of mitogenic cell activation. In addition to these subtle cell-activating effects shared by many viruses, influenza and paramyxoviruses activate a respiratory burst in phagocytic cells. These viruses are toxic when injected in animals. Cells lavaged from the lungs of mice infected with influenza virus are primed for enhanced superoxide generation. Moreover, xanthine oxidase is enhanced and the buffering capacity of small molecular antioxidants is decreased in the lungs, suggesting that infection leads to oxidative stress. The wide array of cytokines produced in the lungs during influenza could contribute to the systemic effects of influenza. Oxidative stress has also been shown in human immunodeficiency virus (HIV) infection in humans. Via activation of NF kappa B, ROS may activate viral replication, but oxidants are believed to contribute also to the loss of CD4 T cells by apoptosis. Antioxidants, together with agents interfering with the harmful effects of cytokines and lipid mediators, may have a role in the treatment of viral diseases. Such agents could not only alleviate disease symptoms but also decrease the long-term effects of chronic oxidative stress, which have been linked to the development of cancer in some viral infections.
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PMID:Oxidants and antioxidants in viral diseases: disease mechanisms and metabolic regulation. 916 74

In the influenza virus infected mice there is a host response which involves free radical generation particularly in the host lung. First, superoxide generation was elevated excessive extent, 200-600 fold in the alveolar lavage fluid (BALF), by induction of xanthine oxidase which becomes maximal at about 8 days after infection while virus yield becomes maximum on day 4. Mice start to die on day 9 although the virus in BALF is undetectable; thus virus disease in the absence of virus. Second, inducible form of nitric oxide synthetase is also triggered exactly in parallel to xanthine oxidase. This indicates NO and O2- is produced simultaneously implicating the formation of peroxynitrite (ONOO-) due to a rapid reaction between NO + O2-. Consequently nitration of lung tissue by ONOO- was demonstrated. ONOO- is also found much toxic than O2- or H2O2 in the cultured cells. Third, proteases are involved in various ways in this infection; activation of xanthine dehydrogenose to xanthine oxidase, activation of viral infectivity and triggering of bradykinin generation and inflammation by activating prekallikrein. Lastly, activation of matrix procollagenase (proMMP) by ONOO- and NO2, generated above, was suggested, which will damage connective tissue. Thus all events involving proteases will augment viral pathogenesis.
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PMID:[Deleterious pathogenic mechanism involving host response in influenza virus infection in mice]. 936 Mar 90

In recent years, accumulated evidence indicates that free radical species and nitric oxide (NO) or its derivatives are the key denominators in carcinogenesis. Our present topics discussed in this article will focus on the biological significance of free radical generation induced by viral and bacterial infections. In influenza virus infection in mice, the level of xanthine oxidase (XO) at the infected sites was elevated to a great extent. The timing of paralleled induction of XO with that of inducible NO synthase (iNOS) indicates efficient simultaneous reaction: NO + O2*- --> ONOO- (peroxynitrite). Peroxynitrite formation was identified by immunostaining of nitrotyrosine at the local site of infected organs. Peroxynitrite exhibits unique chemical reactivities such as protein nitration, DNA-strand breakage, guanine nitration, etc., which may then bring about not only cytotoxic effect but also mutagenesis. Numbers of evidence in vitro and in vivo show that treatment with chemical carcinogens such as carbon tetrachloride and heterocyclic amines also generated superoxide. The chronic inflammatory reactions, e.g., zymosan- and silica-induced granuloma, revealed very similar free radical generation in vivo. In addition, most experimental solid tumors have elevated levels of iNOS in the tumor tissue, and NO thus generated facilitates vascular permeability, which accelerates nutritional supply to the tumor tissue and hence sustains the rapid tumor growth. These circumstantial evidences suggest that inflammatory responses induced by various pathogens would accelerate mutagenesis as well as tissue damage, whereas NO also sustains more effectively solid tumor growth when normal cells are transformed to tumor or carcinoma cells by the host-derived free radical species.
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PMID:Nitric oxide and oxygen radicals in infection, inflammation, and cancer. 972 38

The role of reactive oxygen species (ROS) participating in antiviral host defense is considered. Unlike antibacterial defense, when ROS and their derivatives act as biological weapons killing pathogenic bacteria, the function of ROS in the antiviral defense is assumed to be mediated by apoptosis. It is suggested that a cell activates generation of superoxide and hydrogen peroxide by xanthine oxidase as well as by intracellular NADPH-oxidase in response to appearance of a virus in its cytoplasm. Increase in ROS level turns on the process of programmed cell death in the infected cells. Moreover, H2O2 diffuses into the adjacent cells (due to its high membrane permeability), also inducing apoptosis (death of bystander cells). So, the infected cell and its neighbors (which are the most likely to be infected) are eliminated, thus blocking the spreading of the viral infection.
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PMID:Possible role of reactive oxygen species in antiviral defense. 991 63

Influenza virus infection is associated with development of oxidative stress in lung and blood plasma, viz. increase of primary and secondary lipid peroxidation products. It was established that rimantadine treatment led to a decrease of the products of lipid peroxidation in tissues of mice experimentally infected with influenza virus A/Aichi/2/68 (H3N2). The effect is strongest in blood plasma (a decrease of about 50%) and weaker in the lung (about 20%). To elucidate the mechanism of this action of rimantadine, experiments were carried out with some model systems. The capability of rimantadine to scavenge superoxide radicals (scavenging properties) was studied in a system of xanthine-xanthine oxidase to generate superoxide. The amount of superoxide was measured spectrophotometrically by the NBT-test and chemiluminesce. Rimantadine does not show scavenging properties and its antioxidant effect observed in vivo, is not a result of its direct action on the processes of lipid peroxidation and/or interaction with antioxidant enzymes. The antioxidant properties of rimantadine were investigated by measurement of induced lipid peroxidation in a Fe2+ and (Fe2+ - EDTA) system with an egg liposomal suspension. Our findings with model systems do not prove an antioxidant or prooxidant effect of the drug on the processes of lipid peroxidation. Apparently, the observed antioxidant effect of rimantadine in vivo is not connected directly with free radical processes in the organism.
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PMID:Antioxidant properties of rimantadine in influenza virus infected mice and in some model systems. 1109 38


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