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)

A study was designed to investigate the possibility of reducing peritoneal adhesion formation in mice by pretreatment with allopurinol. Allopurinol, at a dose of 35 mg/kg of body weight/d significantly reduced the severity of peritoneal adhesions (P < .001), and also the neutrophil response to ischemia (P < .05). Tissue myeloperoxidase activity at the site of ischemic injury was significantly lower in the allopurinol-treated mice at the end of 2 weeks (P < .001). However, xanthine oxidase was undetectable in both control and allopurinol-treated mice. These observations suggest that allopurinol reduces the severity of peritoneal adhesion formation in mice, possibly by reducing the neutrophil response to ischemia.
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PMID:Allopurinol reduces the severity of peritoneal adhesions in mice. 759 27

Several pathological situations are characterized by the production of reactive oxygen species (ROS), whereby different sources such as activated leukocytes and xanthine oxidase seem to be mainly responsible. The contribution of immigrating activated neutrophils to symptom development during inflammatory processes or after reperfusion of ischemic tissues is a matter of continuing discussion. We present a simple method for the differentiation between oxygen activating reactions in which neutrophil-derived myeloperoxidase is involved. The method is based on the gas chromatographic detection of ethylene, which is formed by the reaction of alpha-keto-gamma-methylthiobutyric acid (KMB) or 1-amino-cyclopropane-1-carboxylic acid (ACC) with ROS. In the presence of OH-radical-type oxidants, only KMB yields ethylene whereas ACC is fragmented by myeloperoxidase-derived species (OCl-, chloramines). The amounts of ethylene may be used as an indicator for the relative contribution of Fenton-type or myeloperoxidase-catalyzed reactions.
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PMID:Gas chromatographic differentiation between myeloperoxidase activity and Fenton-type oxidants. 764 86

Investigations were carried out to determine the antiulcer effects of silymarin, the hepatoprotective principle of Silybum marianum L. Gaertn., in gastric injury induced by ischemia-reperfusion and its effects on mucosal myeloperoxidase activity, an index of polymorphonuclear leukocyte infiltration, after injury in rats. These results were compared with those from rats that received allopurinol, an inhibitor of xanthine oxidase and with those from rats made neutropenic by prior administration of dexamethasone and methotrexate. Pretreatment with silymarin prevented post-ischemic mucosal injury. The mean ulcer indexes (U.I.) of rats treated with 25, 50 mg, and 100 mg silymarin/kg body weight (4.79 +/- 0.75, 4.50 +/- 0.81, and 3.63 +/- 0.74, respectively) were significantly lower (p < 0.05, 0.05, and p < 0.005) than that of control rats. Allopurinol was considerably more potent in reducing the U.I. than silymarin, with a calculated U.I. of 2.33 +/- 0.45, p < 0.001. These protective effects were specifically related to a reduction in the number of neutrophils in the gastric mucosa. Reduction in the numbers of circulating neutrophils by treating rats with methotrexate (MPO level of 7.2 x 10(-2) +/- 0.56 x 10(-2)U/mg wt) and dexamethasone (MPO level of 6.97 x 10(-2) +/- 0.68 x 10(-2)U/mg wt) also resulted in a significant reduction in the susceptibility to gastric damage induced by ischemia-reperfusion. These results suggest that neutrophils play an important role in the gastric mucosal dysfunction associated with ischemia-reperfusion. These findings also indicate that the inhibitory effects of silymarin on neutrophil function may contribute significantly to its gastroprotective actions.
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PMID:Gastroprotection induced by silymarin, the hepatoprotective principle of Silybum marianum in ischemia-reperfusion mucosal injury: role of neutrophils. 775 16

When stimulated, neutrophils undergo a respiratory burst converting oxygen to superoxide. Although superoxide is critical for microbial killing by phagocytic cells, the precise role it plays has yet to be established. It has been proposed to optimize their production of hypochlorous acid and to be required for the generation of hydroxyl radicals. Superoxide is also involved in the hydroxylation of salicylate by neutrophils. However, the mechanism of this reaction is unknown. We found that neutrophils stimulated with opsonized zymosan hydroxylated salicylate to produce mainly 2,5-dihydroxybenzoate. Its formation was dependent on superoxide and a heme protein but was independent of hydrogen peroxide and hydroxyl radicals. Production of 2,5-dihydroxybenzoate was enhanced by methionine, which scavenges hypochlorous acid. Neutrophils from an individual with myeloperoxidase deficiency hydroxylated salicylate at only 13% of the level of control cells. Purified human myeloperoxidase and xanthine oxidase plus hypoxanthine hydroxylated salicylate to produce 2,5-dihydroxybenzoate. As with neutrophils, the reaction required superoxide but not hydrogen peroxide and was unaffected by hydroxyl radical scavengers. Thus, myeloperoxidase catalyzes superoxide-dependent hydroxylation. This newly recognized reaction may be relevant to the in vivo functions of superoxide and myeloperoxidase.
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PMID:Superoxide-dependent hydroxylation by myeloperoxidase. 800 21

The importance of sequential events which lead to skin necrosis has significant implications in trauma, vascular injury, and wound healing. In this series of experiments, we tested the hypothesis that xanthine oxidase (XO) activity was increased along an ischemic gradient of a skin flap and that the XO enzyme activity correlated with an increase in neutrophils. There were two animal groups in which the skin flaps were raised and assayed at 0, 1, or 6 hr. In the other group, they were created as bipedicle flaps for 7 days, before the distal attachment was divided and the tissue assayed. In the acutely raised flaps, some animals were treated with the XO inhibitor, allopurinol. Xanthine dehydrogenase (XD) and XO activity was measured with a fluorometric pterin assay and neutrophil concentration was measured using a myeloperoxidase marker. In this model, there was consistent skin necrosis in the distal end of the skin flap (48 +/- 8%). The data showed that both XD and XO activity in the distal ends was statistically significantly increased over the sham control or proximal ends of the skin flaps at 1 hr (P < 0.05). XO activity remained elevated in the distal ends at 6 hr. Allopurinol significantly reduced the neutrophil concentrations in the distal ends of the skin flaps when compared to untreated animals (P < 0.05). Moreover, allopurinol reduced skin necrosis to 12 +/- 1%. Preconditioning of the skin flap reduced the XO activity to sham control levels. The observations implicate XO activity as source of free radical injury in skin necrosis seen in random skin flaps.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of xanthine oxidase and xanthine dehydrogenase in skin ischemia. 812 Nov 73

Premature infants are susceptible to intestinal ischemia during the newborn period when their intestinal tracts are functionally and structurally immature. Studies have shown that exogenous glucocorticoids hasten intestinal maturation. We investigated the effects of hydrocortisone on platelet activating factor (PAF)-induced intestinal ischemia in the neonatal rat. On Postnatal Days 7-11, Sprague-Dawley rats were given intraperitoneal (ip) injections of either saline (SAL) or hydrocortisone (HC; 50 mg/kg total). On Day 12, rats were injected with either PAF (2 micrograms/kg) or an equal volume of saline. After 2 hr the rats were sacrificed and sections were taken for histology. The remaining intestine was analyzed for maltase, lactase, myeloperoxidase (MPO), and xanthine oxidase (XO). Experimental groups were as follows: SAL (N = 8), received saline only; SAL+PAF (N = 8), received saline plus PAF; HC (N = 3), received hydrocortisone+saline; and HC+PAF (N = 5), received hydrocortisone plus PAF. XO was significantly decreased (P < 0.001) in the hydrocortisone-treated groups (HC + SAL = 16.36 +/- 18.42 units/g protein, HC + PAF = 17.33 +/- 9.06 units/g protein) vs the controls (SAL only = 108.90 +/- 20.24 units g/protein, SAL + PAF = 145.77 21.28 units/g protein). MPO was not significantly elevated in SAL + PAF (4.60 +/- 0.95 units/g protein) vs HC + PAF (2.18 +/- 0.80 units/g protein) in this study. Maltase was significantly elevated (P < 0.001) in the HC + PAF (241.46 +/- 40.6 mole/min/g protein) and HC + SAL (152.78 +/- 16.35 mole/min/g protein) vs saline only (28.35 +/- 5.77 mole/min/g protein and SAL + PAF (37.29 +/- 8.70 mole/min/g protein. Animals (7/8) in the SAL + PAF group developed ischemia by inspection and histologic exam.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intestinal ischemia in the newborn: the role of intestinal maturation. 824 92

This study was conducted with rats to assess the involvement of leukocytes in a model of CO-mediated brain injury. Myeloperoxidase activity, measured as an index of leukocyte sequestration, was found to be increased 10-fold in brain microvessel segments prepared from rats immediately or 90 min after exposure to CO. Fluorescence and light microscopic examinations revealed leukocytes in microvessels taken from CO-poisoned rats, but not in that from control rats. Studies were then conducted with rats that had been made leukopenic or treated with monoclonal anti-CD-18 F(ab')2 fragments to inhibit leukocyte adherence to the vasculature. Neither of these groups of animals exhibited the biochemical changes observed in the brains of sham-treated rats: conversion of xanthine dehydrogenase (XD) to sulfhydryl-irreversible xanthine oxidase (XO), and lipid peroxidation, at 90 min following CO poisoning. Treatment with a synthetic serine protease inhibitor, gabexate mesylate, also prevented these biochemical changes if administered immediately after CO poisoning, but the agent did not inhibit leukocyte sequestration. Rats depleted of XD and XO by a tungsten diet, and those treated with allopurinol to inhibit XD and XO, also exhibited at least a 10-fold increase in myeloperoxidase activity in microvessels immediately after CO poisoning, but only a 5-fold increase at 90 min. In vitro studies demonstrated that B2 integrin-dependent polymorphonuclear leukocyte adherence was impaired immediately following CO poisoning although the adherence molecules were expressed on the membrane surface. Adherence function normalized by 45 min. The results suggest that leukocytes are responsible for the development of biochemical changes in brain following CO poisoning, and the sequence of events is as follows: leukocyte sequestration in the microvasculature, B2 integrin-dependent adherence, protease-mediated conversion of XD to XO, O2 radical-dependent lipid peroxidation.
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PMID:Leukocytes in carbon monoxide-mediated brain oxidative injury. 824 31

Exposure to hyperbaric oxygen [3 atmospheres absolute (ATA) for 45 min] inhibited carbon monoxide (CO)-mediated lipid peroxidation in the brains of rats by preventing the conversion of xanthine dehydrogenase to oxidase, a conversion process known to be due to the action of leukocytes. The effect was the same whether treatment was given 24 hr before or up to 45 min after poisoning. Hyperbaric oxygen did not inhibit the initial interaction of leukocytes with brain microvasculature, based on measurements of myeloperoxidase (MPO) in microvessel segments, but persistent adherence, which is due to B2 integrins, did not occur. Exposing rats to 3 ATA pressure (0.21 ATA O2) after CO poisoning had no significant effects. A progressive reduction in brain microvessel MPO titers occurred with exposure to O2 at 1, 2, or 3 ATA after CO poisoning, but 1 ATA O2 treatment did not significantly inhibit xanthine oxidase formation or lipid peroxidation. In vitro studies with polymorphonuclear leukocytes (PMN) from rats exposed to hyperbaric oxygen corroborated the absence of PMN B2 integrin function, but when these cells were stimulated they exhibited normal B2 integrin expression on their surface and also normal elastase release and superoxide radical production. Adherence functions of PMN that do not require B2 integrins appeared to remain intact after exposure to hyperbaric oxygen, as peritoneal neutrophilia in response to a glycogen challenge was not inhibited. B2 integrin function could be restored by incubating cells with 8 bromo cGMP, and incubation with phorbol ester stimulated the adherence function of both control and hyperbaric oxygen-exposed PMN. These results provide a clear mechanism for the inhibition of CO-mediated brain lipid peroxidation by hyperbaric oxygen and indicate that hyperoxia causes a discrete disturbance of PMN adherence function.
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PMID:Functional inhibition of leukocyte B2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats. 824 32

Myeloperoxidase, the most abundant enzyme in neutrophils, catalyses the conversion of hydrogen peroxide and chloride to hypochlorous acid. This potent oxidant has the potential to cause considerable tissue damage in many inflammatory diseases. We have investigated the ability of dapsone, diclofenac, primaquine, sulfapyridine and benzocaine to inhibit hypochlorous acid production by stimulated human neutrophils. The drugs were also tested against purified myeloperoxidase using xanthine oxidase to generate hydrogen peroxide and superoxide. The inhibitory effects of the drugs on hypochlorous acid production, either by cells stimulated with phorbol myristate acetate or by myeloperoxidase and xanthine oxidase, were significantly less than those determined with myeloperoxidase and reagent hydrogen peroxide. Comparable potency was observed only when superoxide dismutase was present to remove superoxide. We also observed that with the xanthine oxidase system, inhibition of hypochlorous acid production by dapsone decreased markedly as the concentration of myeloperoxidase increased. Dapsone was a poor inhibitor of hypochlorous acid production by neutrophils stimulated with opsonized zymosan, regardless of the presence of superoxide dismutase. With this phagocytic stimulus, catalase inhibited hypochlorous acid formation by only 60%, which indicates that a substantial amount of the hypochlorous acid detected originated from within phagosomes. Thus, it is apparent that dapsone is unable to affect intraphagosomal conversion of hydrogen peroxide to hypochlorous acid. All the drugs inhibit myeloperoxidase reversibly by trapping it as its inactive redox intermediate, compound II. We propose that superoxide limits the potency of the drugs by reducing compound II back to the active enzyme. Furthermore, under conditions where the activity of myeloperoxidase exceeds that of the hydrogen peroxide-generating system, which is most likely to occur in phagosomes, partial inhibition of myeloperoxidase need not affect hypochlorous acid production. We conclude that drugs that inhibit myeloperoxidase by converting it to compound II are unlikely to be effective against hypochlorous acid-mediating tissue damage.
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PMID:Superoxide is an antagonist of antiinflammatory drugs that inhibit hypochlorous acid production by myeloperoxidase. 839 Feb 58

Recent evidence has suggested that the immaturity of the neonatal intestine may play a key role in the development of ischemic injury. However, relatively little data exist on the susceptibility of the neonatal intestine to ischemic injury at various ages especially in the fed versus fasted states. In this study, the levels of xanthine oxidase ([XO] an enzyme which is a known, major source of free radicals in postischemic tissue) and myeloperoxidase ([MPO] an index of tissue neutrophil infiltration) were measured in 1-, 5-, 10-, 15-, and 20-day-old Sprague-Dawley rats. Rats were divided into fed (n = 8/day) and fasted (n = 8/day) groups 4 hours prior to sacrifice. The entire small intestine was removed and divided into five segments: the duodenum, proximal jejunum, distal jejunum, proximal ileum, and distal ileum. The specimens were homogenized and assayed for XO and MPO levels. A significant increase in XO was observed in the fasted animals compared to the fed animals on all days. Peak levels in XO were observed in both groups from day 5 to 10. MPO levels were significantly higher in the fasted versus fed animals on day 1. MPO levels decreased as the animals aged. These data demonstrate dramatic differences in the levels of inflammatory enzymes of the newborn rat in the fed versus fasted states. Also, marked variations with age are seen in both XO and MPO. Whether the XO and MPO levels present at the time of ischemic insult affect severity of injury remains to be seen.
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PMID:Inflammatory enzyme composition of the neonatal rat intestine: implications for susceptibility to ischemia. 839 43


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