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)

Reperfusion injury following ischemia is thought to be the consequence of reactive oxygen species possibly generated either by xanthine oxidase activity or by processes associated with neutrophil activation in the affected organ or tissue. The conversion of xanthine dehydrogenase to the oxidase as well as the interactions between endothelium and neutrophils in the margination and activation of the latter are all considered to be results of conditions resulting from the ischemic episode. Determination of the redox status of glutathione in an ischemic/reperfused organ is frequently employed as an indicator of oxidative stress created by the production of oxygen free radicals during the reperfusion period. In this procedure, the ratio of oxidized glutathione (GSSG) to total glutathione (GSH + GSSG) is utilized to demonstrate the proportion of glutathione oxidized during reperfusion. We determined this ratio in the rat small intestine during ischemia and reperfusion and found that while the ratio of GSSG/(GSH + GSSG) does increase, this increase was the result of GSH disappearance rather than an increase in GSSG, and that essentially all of this loss occurred during the ischemic episode. We demonstrated that no oxidation of GSH occurred that was attributable to reperfusion per se; nor was there an increase of GSSG during this reoxygenation period.
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PMID:Evidence that the large loss of glutathione observed in ischemia/reperfusion of the small intestine is not due to oxidation to glutathione disulfide. 846 26

The protective effect of N-acetylcysteine (NAC) against oxidant lung injury was investigated in a model of acute immunological alveolitis in the rat. Intrapulmonary immune complex deposition into rat lungs, induced by intratracheal infusion of immunoglobulin G (IgG) anti-bovine serum albumin (BSA) antibodies and intravenous injection of the antigen, caused lung damage associated with a marked decrease in [14C]5-hydroxytryptamine ([14C]5HT) uptake capacity, taken as a biochemical marker of endothelial cell function. The oral administration of a single dose of NAC (2 mmol.kg-1) 60 min before antigen/antibody (Ag/Ab) treatment was effective in preventing pulmonary endothelial cell [14C]5HT uptake loss induced by immune complex deposition. The mechanisms involved in this lung protective action of NAC were investigated by studying the antioxidant activity of NAC on hypoxanthine/xanthine oxidase-induced lung damage in vitro, and the effectiveness of the drug as lung glutathione (reduced form) (GSH) precursor in diethylmaleate-depleted rats. The results obtained provide further evidence on the ability of NAC to reduce the susceptibility of lung tissue to free radical-induced damage, by potentiating the antioxidant defence systems.
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PMID:Protection by N-acetylcysteine against pulmonary endothelial cell damage induced by oxidant injury. 847 21

The ability of endogenous glutathione (GSH) to modify the activity of the enzyme xanthine oxidase (XO) in rat liver was investigated. The effect of hepatic GSH depletion on the conversion of xanthine dehydrogenase (XDH) (EC 1.1.1.204) to XO (EC 1.1.3.22) was determined 10 min after i.p. administration of different amounts of diethylmaleate to fasted rats. After administration of 400 mg/kg, total hepatic non-protein GSH (reduced + oxidized GSH) decreased significantly to 14% of controls. In this condition the level of oxidized GSH was unchanged and no lipid peroxidation was observed, while a significant increase of reversible XO and a minor increase of the irreversible form of the enzyme was detected.
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PMID:Effect of glutathione depletion on the conversion of xanthine dehydrogenase to oxidase in rat liver. 851 79

To determine whether antioxidant mechanisms within red blood cells (RBCs) significantly contribute to preserving hypoxic pulmonary vasoconstriction (HPV) in both the absence and the presence of oxidative stress, we investigated HPV changes in isolated rabbit lungs perfused with solutions containing RBCs treated with various inhibitors of superoxide dismutase (SOD), anion channels, catalase (CAT), or glutathione peroxidase (GSH-Px). Perfusion was maintained at a constant flow rate of 70 ml/min, and lung temperature at 37 to 38 degrees C. Hematocrit was adjusted to 7%. In the absence of overt oxidative stress, HPV was significantly enhanced in the perfusate containing control RBCs (untreated RBCs) as compared with that in Krebs-Henseleit buffer. Inhibition of SOD, CAT, and GSH-Px within RBCs, as well as anion channels located on the RBC membrane, had little influence on HPV. Neither exogenous SOD nor CAT altered HPV. In the presence of high levels of reactive oxygen species (ROS), generated by addition of xanthine (100 microM) and xanthine oxidase (10 mU/ml) to the reservoir, HPV was considerably suppressed in the perfusate containing only buffer but was restored in the perfusate with control RBCs. Inhibition of CAT or GSH-Px in RBCs preserved the HPV, whereas inhibition of SOD or anion channels failed to preserve HPV obtained during exposure to high ROS levels. Addition of exogenous SOD, but not CAT, to the perfusate containing RBCs in which endogenous SOD had been inhibited restored HPV under high ROS conditions. In conclusion, (1) although RBCs augment HPV in the absence of ROS, this finding is not attributable to the antioxidants in RBCs. (2) RBCs restore HPV upon exposure to high ROS. This finding may well be explained by antioxidant mechanisms operating within RBCs, especially those of endogenous SOD.
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PMID:Modulation of hypoxic pulmonary vasoconstriction by antioxidant enzymes in red blood cells. 854 18

In order to develop an efficient antioxidant therapeutic regime for inflammatory disease in the lung N-acetylcysteine (NAC) and reduced glutathione (GSH) were tested to inhibit O2 and H2O2 in vitro and ex vivo. NAC and GSH inhibited both at > or equal to 10(-4)M significantly H2O2 (5 x 10(-8)) mol/ml; p < 0.05). In contrast, in an assay consisting of xanthine/xanthine oxidase/ferricytochrome c Cu++/Zn++ superoxide dismutase (SOD), but not NAC and GSH had an anti-O2 effect (SOD: at > or equal to 10(-5)M, p < 0.01 when compared with 0). In accordance with these results, NAC and GSH had good anti-H2O2 efficacy in freshly isolated and ex vivo cultured mononuclear (MN) and polymorphonuclear cells (PMN) derived from patients with COPD (smoker, n = 30). Both drugs reduced H2O2 significantly when used in concentrations already at > or equal to 10(-9)M (p < 0.05). However, neither GSH nor NAC influenced O2 produced by these inflammatory cells effectively. Antioxidative properties of NAC are well explained by the SH-group within the molecular structure which can be oxidized by certain oxygen radicals. Good H2O2 scavenger function ex vivo, which seems to contradict the results obtained in vitro, illustrates additional cellular GSH-precursor efficacy of both substances in cell dependent assay systems. Thus, to achieve direct anti-H2O2 efficacy in vivo high local NAC concentrations (10(-4)M)) are necessary.
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PMID:[N-acetylcysteine: a functional oxygen radical scavenger in vitro and ex vivo in monocytes and neutrophilic granulocytes of patients with COPD]. 858 24

Glutathione (GSH) is the most important cytosolic antioxidant. Since GSH levels are decreased with age, we hypothesized that T-lymphocytes from old mice would be more sensitive to oxidative stress. T-lymphocytes from young and old mice were exposed to hypoxanthine/xanthine oxidase, and lymphocyte viability, proliferation, GSH content, and calcium signaling were measured. Before exposure, proliferation of T-lymphocytes from young mice was greater than that of old; following exposure, the converse was true. This was in spite of the fact that old mice had lower total GSH levels and greater levels of glutathione disulfide. After oxidative challenge, intracellular calcium responses to anti-CD3 were decreased in naive T-lymphocytes from all mice, while memory lymphocytes were less affected. Higher proportions of memory lymphocytes in old mice resulted in their greater overall preservation of lymphocyte function following oxidative injury, contrary to expectations that lower lymphocyte GSH content with age would increase susceptibility to oxidative stress.
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PMID:Aged murine T-lymphocytes are more resistant to oxidative damage due to the predominance of the cells possessing the memory phenotype. 861 97

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

The peroxidation of lipids and changes in the activities of related enzymes in the gastric mucosa were studied in a rat model of gastric mucosal injury induced by the nonsteroidal anti-inflammatory drug indomethacin. The area of gastric erosion and the amount of thiobarbituric acid reactive substances (TBARS) in gastric mucosa were significantly increased beginning 4h after administration of indomethacin. Xanthine oxidase (XOD) activity in the gastric mucosa also increased immediately after administration of the drug. Although XOD activity was significantly suppressed by allopurinol treatment, the induction of gastric mucosal injury and the increase of TBARS in the gastric mucosa were not. Myeloperoxidase (MPO), a marker enzyme of leukocytes, was unaffected by indomethacin administration. But the depletion of polymorphonuclear leukocyte (PMN) counts induced by an injection of anti-rat PMN antibody inhibited both the injury and the increase in TBARS. Indomethacin activated PMN in peripheral blood at 30mg/kg per as and enhanced release of oxygen radicals from PMN in peripheral blood. As compared with the XOD system, the generation of oxygen free radicals may derived mainly from activated PMN. On the other hand, superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) were reduced by the administration of indomethacin. Decreases in SOD and GSH-px activity in gastric mucosa may aggravate mucosal injury by free radicals and lipid peroxidation.
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PMID:Lipid peroxidation in gastric mucosal lesions induced by indomethacin in rat. 874 81

Levels of uric acid, xanthine, hypoxanthine, ascorbic acid (AA), dehydroascorbic acid (DHAA), glutathione (GSH), noradrenaline (NA), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ion (MPP+) were determined in the striatum and/or in the brain stem of 3-month-old male Wistar rats given allopurinol (300 mg/kg day by gavage) for 3 days before a single MPTP 35 mg/kg dose IP. Allopurinol alone decreased uric acid and increased xanthine levels both in the striatum and in the brain stem; moreover, allopurinol decreased striatal DOPAC + HVA/DA ratio and increased 5-HIAA/5HT ratio in the brainstem. Allopurinol affected neither regional MPTP nor MPP+ disposition. Allopurinol potentiated the MPTP-induced decrease in the DOPAC+HVA/DA ratio and increase in striatal AA oxidation; in addition, allopurinol antagonised the MPTP-induced: (i) increase in uric acid levels; (ii) decrease in NA levels in both regions, in DA levels, and in the 5-HIAA/5-HT ratio in the brain stem: (iii) increase in AA oxidation in the brain stem. In conclusion, the MPP(+)-induced oxidative stress mediated by xanthine oxidase seems to be involved in DA depletion in the brainstem and in NA depletion in both regions; moreover, striatal uric acid may have an active role in the neuronal antioxidant pool.
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PMID:Further investigation of allopurinol effects on MPTP-induced oxidative stress in the striatum and brain stem of the rat. 874 98

Oxalate, the major stone-forming constituent induces lipid peroxidation during lithogenesis. In experimental condition oxalate formation was induced by the administration of its precursor glycollate. Glycollate-fed rats showed increased susceptibility to lipid peroxidation in the presence of promoters. In addition, antioxidant enzymes-catalase, superoxide dismutase and glutathione peroxidase also showed decreased activity. Reduced glutathione, total thiols and ascorbic acid were also significantly decreased. On the other hand, an increased xanthine oxidase and decreased glucose-6-phosphate dehydrogenase activity was also observed upon glycollate administration. Cysteine, a sulphydryl compound, is known to inhibit free radical toxicity in various pathologies. Cysteine administration to glycollate-fed rats brought about a significant decrease in the peroxidative level, with an increase in the antioxidant status.
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PMID:Effect of L-cysteine on lipid peroxidation in experimental urolithiatic rats. 874 47


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