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)

The effects of reactive oxygen species (ROS) on cultured rat mesangial cells were studied by measuring planar cell surface area (PCSA) after incubation with xanthine plus xanthine oxidase (XXO), in the presence of superoxide dismutase (SOD; 5 micrograms/ml) or catalase (CAT; 20 micrograms/ml), or after incubation with H2O2. Myosin light chain (MLC) phosphorylation was assessed in cells prelabeled with o-[32P]phosphoric acid and incubated with H2O2, after protein separation with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A possible intermediate role for platelet-activating factor (PAF) was analyzed by preincubation of the cells with a PAF antagonist BN 52021 (BN, 5 x 10(-5) M) and by measuring PAF-specific [3H]acetate incorporation and immunoassayable PAF. XXO significantly decreased PCSA (14%), an effect abolished by CAT but not by SOD. H2O2 induced a similar effect, in a dose-dependent and time-dependent manner. MLC phosphorylation increased by 81 +/- 15% after H2O2 incubation, and this effect was blocked by BN. BN also completely blocked the effect of H2O2 on PCSA. PAF-specific [3H]acetate incorporation increased in the presence of H2O2 (from 6,886 +/- 2,030 to 58,703 +/- 16,063 counts.min-1.mg-1) as well as the immunoassayable PAF production by cells (from 0.90 +/- 0.19 to 6.71 +/- 2.27 ng/mg). These results suggest that ROS, particularly H2O2, could modulate the surface area of mesangial cells, modifying the ultrafiltration coefficient, thus explaining the decrease in glomerular filtration rate in those pathological situations characterized by an increased ROS synthesis. PAF could be involved in the genesis of these effects.
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PMID:Effects of reactive oxygen species on cultured rat mesangial cells and isolated rat glomeruli. 141 75

Low-density lipoproteins (LDL) oxidized by oxygen radicals (OR) 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 may induce foam cells transformation. 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). It is unknown whether LDL are modified via direct lipid oxidation by OR, or whether LDL are subsequently oxidized via chain reactions after initial OR attack. To distinguish between these 2 mechanisms, LDL were exposed to OR formed by xanthine/xanthine oxidase (X/XO). Peroxidation was measured from malonyldialdehyde (MDA) levels. Parallel experiments were performed in presence of the superoxide radical scavenger superoxide dismutase (SOD; 330 U/ml), or the hydrogen peroxide scavenger catalase (CAT; 1000 U/ml), or by adding the chain-reaction inhibitor butylhydroxytoluene (BHT; 1 mM) at selected time points. SOD, but not CAT prevented LDL peroxidation, indicating an obligatory role for superoxide radicals. Superoxide generation in this model lasts only a few minutes, however, MDA levels continued to increase over several hours. Furthermore, this phenomenon was blocked when BHT was added at various times after X/XO. These data show that LDL peroxidation is triggered by initial OR generation but then involves chain reactions which do not require continuous exposure to OR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Human low-density lipoproteins are peroxidized by free radicals via chain reactions triggered by the superoxide radical]. 166 2

The purpose of this study was to determine if the bronchoconstriction and airway hyperresponsiveness (AHR) resulting from aerosolized xanthine (x; 0.1%)-xanthine oxidase (xo; 4.1 U) and the subsequent production of oxygen radicals is mediated by the secondary generation of lipid mediators. In seven conscious sheep, specific lung resistance (SRL) was measured before and after x-xo challenge; approximately 30 min later when SRL had returned to baseline, airway responsiveness to carbachol was determined from dose-response curves by calculating the cumulative provocating dose of carbachol in breath units (BU, defined as one breath of a 1% wt/vol carbachol solution) that increased SRL 400% over baseline (PD400). Inhaled x-xo caused in immediate increase in SRL of 162 +/- 36% (mean +/- SE; p less than 0.05) over baseline and decreased PD400 from a baseline value of 32.5 +/- 5.0 to 16.6 +/- 1.7 BU (p less than 0.05). Pretreatment with the H2O2 scavenger, catalase (CAT,; 38 mg aerosol), methylprednisolone succinate (MS; 1 mg/kg given intravenously), the cyclooxygenase inhibitor, indomethacin (IND; 2 mg/kg given intravenously), and the PAF antagonist, WEB-2086 (3 mg/kg given intravenously) all attenuated the x-xo-induced increase in SRL (p less than 0.05); the leukotriene D4 antagonist, MK-571 (5 mg by aerosol) had no effect. All agents inhibited the x-xo-induced decrease in PD400: mean BUs were 27 after CAT, 32 after WEB-2086, 34 after IND, 31 after MS, and 25 after MK-571 (all p less than 0.05 versus x-xo alone).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipid mediators contribute to oxygen-radical-induced airway responses in sheep. 174 41

Oxygen free radicals (OFRs) generated during reperfusion are putative mediators of postischemic renal dysfunction. To address this issue, the renal response to ischemia and reperfusion was compared to the response to OFR generation without ischemia. Isolated rat kidneys were perfused at 37 degrees C and 90-100 mm Hg with an asanguinous modified Krebs' buffer. Kidneys were subjected to 30 min of ischemia followed by reperfusion or to OFRs generated by combining 25 mumole hypoxanthine with 1 unit xanthine oxidase. Both insults caused a 50% increase in vascular resistance. This was accompanied by a 30% reduction in perfusate flow rate and an 80% reduction in glomerular filtration and urine flow rates. The OFR scavengers, superoxide dismutase (SOD, 250 units/ml) and catalase (CAT, 500 units/ml), prevented these alterations after OFR generation but not after 30 min of ischemia and reperfusion. SOD and CAT also afforded no protection against the less severe dysfunction observed after 10 or 20 min of ischemia and reperfusion. OFRs do not appear to be prominent mediators of postischemic renal dysfunction; other factors, probably associated with ischemia must be primarily responsible.
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PMID:Postischemic renal dysfunction: the limited role of xanthine oxidase-generated oxygen free radicals. 226 85

In the feline intestine studies have implicated superoxide (O.-) and other oxygen derived free radicals as initiators of injury as measured by increased capillary permeability during the reperfusion period. Biochemical mechanisms of this free radical generation include: xanthine oxidase dependent O.- production, hydrogen peroxide (H2O2) formation by superoxide dismutase (SOD), hydroxyl radical (OH-) production via the Haber-Weiss reaction, and lipid radical formation from membrane peroxidation. Pathological consequences of these events include inflammatory neutrophil infiltration, damage to the collagen and mucosal basement membrane, increased capillary permeability, edema, cell degeneration and necrosis. Animal models of neonatal necrotizing enterocolitis (NNEC) indicate that intestinal injury occurs after the etiologic factors (hypothermia, hypoxia) are removed. In order to determine the role of active oxygen species in the pathogenesis of NNEC, weanling hamsters and neonatal piglets were cold stressed and activities of pro/antioxidant enzymes were determined, and histopathologic and ultrastructural studies were performed. Cold stressed weanling hamsters showed a 55.7% (P less than 0.05) decrease in xanthine dehydrogenase/xanthine oxidase activity ratio. Light microscopy revealed scattered colonic mucosal erosions and submucosal edema in 50% of cold stressed animals. Transmission electron microscopy demonstrated degeneration of colonic mucosal epithelial cells, enlarged intracellular spaces, cytoplasmic vacuolization, and nuclear membrane swelling. The colonic serosa was also edematous and infiltrated with bacteria. Large intestinal tissue from cold stressed neonatal piglets showed a significant increase (P less than 0.05) in Mn and Cu, Zn, SOD, CAT, GSH-Red, total GSH, and Glc6-PD at 0 and 12 hrs. post stress.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intestinal post-ischemic reperfusion injury: studies with neonatal necrotizing enterocolitis. 259 24

We investigated the role of free radicals, especially from activated neutrophils, in acute xanthine and xanthine oxidase-induced lung injury in rats. We evaluated the effects of intravenously administered intracellular and extracellular free radical scavengers (for O2-., H2O2, and .OH), methylprednisolone (MP), and Ulinastatin (UST, a protease inhibitor), on this animal model of lung injury. At 5 min prior to the intrabronchial injection of a mixture of xanthine (X, 100 nmol) and xanthine oxidase (XO, 1 unit) used to induce unilateral lung damage, rats were pretreated intravenously with superoxide dismutase (SOD, 40 mg/kg), SOD (40 mg/kg) plus catalase (CAT, 30 mg/kg), dimethylthiourea (DMTU, 500 mg/kg), N-2-mercaptopropionyl glycine (MPG, 20 mg/kg), MP, 30 mg/kg, and UST, 50,000 units/kg. Each scavenger was infused intravenously at one-half the initial dose for 20 min after intrabronchial injection; 3 hr later, we examined the wet/dry lung weight ratios and the levels of thiobarbituric acid-reactive substances (TBARS) in lung tissue. Intrabronchial injection of the X/XO mixture markedly increased wet/dry lung weight ratios and lung tissue content of TBARS. Histopathologic changes were observed in the injected lung as well. Pretreatment with SOD + CAT, DMTU, and UST significantly reduced the increases in wet/dry lung weight ratios and lung tissue content of TBARS induced by the intrabronchial injection of the X/XO mixture. Our data suggest indirectly that free radicals (H2O2, .OH) and proteases from activated neutrophils may contribute, in part, to the lung damage induced by the O2-.-generating system of xanthine and xanthine oxidase.
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PMID:Effects of free radical scavengers, methylprednisolone, and ulinastatin on acute xanthine and xanthine oxidase-induced lung injury in rats. 783 23

In this study, the activities of major enzymes participating in free radical metabolism (xanthine oxidase, XO; Cu,Zn and Mn superoxide dismutases, SOD; glutathione peroxidase, GSH-Px; catalase, CAT) were measured in kidney tissues from guinea pigs treated with gentamicin alone (200 mg/kg/day), gentamicin plus vitamin C (600 mg/kg/day), gentamicin plus vitamin E (400 mg/kg/day), and gentamicin plus vitamins C and E together for 10 days, and from animals treated with physiological saline solution alone during this period. We found no significant differences between control and gentamicin groups with respect to XO and Cu,Zn-SOD activities. However, the activities of Mn-SOD, GSH-Px, and CAT were found to be significantly depressed in the gentamicin-treated group relative to controls. In the gentamicin plus vitamin C group, the renal tissue Mn-SOD activity was found to be higher as compared with control and gentamicin groups. In this group, XO, GSH-Px and CAT activities were also higher than in the gentamicin-treated group, but no statistically significant differences existed between the values of this group and controls. Similar results were also observed in the gentamicin plus vitamin E group for Mn-SOD, GSH-Px, CAT, and XO. In this group, the Cu,Zn-SOD activity was found to be decreased as compared with control and gentamicin groups. In the gentamicin plus vitamins C and E group, the Cu,Zn-SOD activity was found to be decreased, the XO activity to be unchanged, and Mn-SOD, GSH-Px, and CAT activities to be increased as compared with the gentamicin and control groups. The results suggest that the enzymatic antioxidant defense system was significantly disturbed because of the suppressed activities of Mn-SOD, GSH-Px, and CAT in the kidney tissues from animals treated with gentamicin. However, vitamins C and E given concurrently with gentamicin completely abrogated this enzymatic suppression.
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PMID:Reduced enzymatic antioxidant defense mechanism in kidney tissues from gentamicin-treated guinea pigs: effects of vitamins E and C. 868 38

Several studies indicate that reactive oxygen species (ROS) are involved in defective sperm function pathophysiology. In this study we attempted to determine differentially the effects of xanthine (0.12 mM) plus xanthine oxidase (0.035 U/mL) (X+XO, a ROS promoter system), ROS scavengers (Tiron (TIR, 15 mM); catalase (CAT, 10 micrograms/mL); dimethylsulfoxide (DMSO, 140 mM)), and X+XO plus scavengers on several epididymal mouse spermatozoa functional parameters, incubated in NTPC medium, for 29 min. In the presence of X+XO, progressive gametes significantly diminished. TIR or CAT attenuated this effect, but DMSO did not. Inversely, X+XO increased the bending-forms population; only TIR reversed this phenomenon. The ROS promoter system diminished the viable cell population; all scavengers assayed maintained sperm viability at levels similar to control ones. When exposed to hypoosmotic shock after 29 min incubation with X+XO, the percentage of swollen cells decreased; TIR, CAT, or DMSO did not prevent this effect. Our experiments demonstrate that it is possible to differentiate the deleterious ROS effects upon sperm functional activity. O-2. and H2O2 preferentially seem to modify sperm motility, O-2. exhibiting the greatest ability for generating bending-form gametes, OH-being the most lethal ROS. In addition, sperm membrane clearly appears as the most damaged structure.
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PMID:Differential effects of pharmacologically generated reactive oxygen species upon functional activity of epididymal mouse spermatozoa. 916 98

The aim of this study was to determine whether the administration of free radical antagonists, immediately before and during the early minutes of reperfusion, improves muscle survival 24 hr after a period of ischemia. Rabbit rectus femoris muscles were isolated, made ischemic for 3 1/2 hr and treated with either desferrioxamine (DFX), an Fe3+ chelator, superoxide dismutase and catalase (SOD & CAT), which quench superoxide and hydrogen peroxide, or allopurinol, an inhibitor of xanthine oxidase (XO). After 24 hr reperfusion, muscle viability (+/-s.e.m.), measured by the nitro blue tetrazolium (NBT) vital staining technique, was 41.6 +/- 11.3% for saline-treated ischemic controls, 30.6 +/- 7.6% for DFX-treated, 46.7 +/- 10.3% for SOD & CAT-treated, and 43.3 +/- 9.5% for allopurinol-treated muscles. None of the treated groups differed significantly from the ischemic control group. Tissue myeloperoxidase, ATP and reduced glutathione levels, and plasma lactate dehydrogenase (LDH) and aspartate transaminase (AST) levels were increased by ischemia and reperfusion in all groups, but the changes did not differ between the treatment groups. Levels of XO in the rabbit muscle were determined and found to be very low in both normal and postischemic muscle. As XO is the target enzyme of allopurinol, its absence provides a basis for the lack of effect of this agent. However, it is not clear why DFX and SOD & CAT had no protective effect.
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PMID:Influence of postischemic administration of oxyradical antagonists on ischemic injury to rabbit skeletal muscle. 939 70

Crosslinking hemoglobin with superoxide dismutase and catalase (PolyHb-SOD-CAT) helps to limit free radical reactivity of modified hemoglobin red blood cell substitutes. In the present study, in vitro oxidant challenge experiments were performed with exogenous hydrogen peroxide (H2O2) and xanthine oxidase-derived superoxide (O2.-). PolyHb-SOD-CAT was compared to PolyHb for the presence of secondary hemoprotein-free radical events. PolyHb-SOD-CAT prevents ferrylhemoglobin formation, measured as Na2S-induced absorbance at 620 nm. Similarly, PolyHb-SOD-CAT inhibited ferrozine-detectable iron release at high oxidant-heme ratios. The formation of oxygen radicals, monitored by salicylate hydroxylation, was prevented at high oxidant-heme ratios with PolyHb-SOD-CAT. The peroxidation of liposomal membranes was also inhibited in PolyHb-SOD-CAT mixtures subject to oxidant challenge. These results show that PolyHb-SOD-CAT prevents secondary hemoprotein-associated free radical events. This new type of modified hemoglobin oxygen carrier with antioxidant activity may reduce the potential toxicity of hemoglobin-based substitutes in certain applications, especially during reperfusion of ischemic tissues.
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PMID:Absence of hemoprotein-associated free radical events following oxidant challenge of crosslinked hemoglobin-superoxide dismutase catalase. 960


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