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)

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 the present study, we investigated the effects of high levels of dietary fish oil on the growth of MX-1 human mammary carcinoma and its response to mitomycin C (MC) treatment in athymic mice. We found that high levels of dietary fish oil (20% menhaden oil + 5% corn oil, w/w) compared to a control diet (5% corn oil, w/w) not only lowered the tumor growth rate, but also increased the tumor response to MC treatment. We also found that high levels of dietary fish oil significantly increased the activities of tumor xanthine oxidase and DT-diaphorase, which are proposed to be involved in the bioreductive activation of MC. Since menhaden oil is highly unsaturated, its intake caused a significant increase in the degree of fatty acid unsaturation in tumor membrane phospholipids. This alteration in tumor membrane phospholipids made the tumor more susceptible to oxidative stress, as indicated by the increased levels of both endogenous lipid peroxidation and protein oxidation after feeding the host animals the menhaden oil diet. In addition, the tumor antioxidant enzyme activities, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPOx), and glutathione S-transferase peroxidase (GSTPx), were all significantly enhanced by feeding a diet high in fish oil. MC treatment caused further increases in tumor lipid peroxidation and protein oxidation, as well as in the activities of CAT, SOD, GPOx, and GSTPx, suggesting that MC causes oxidative stress in this tumor model which is exacerbated by feeding a diet high in menhaden oil. Thus, feeding a diet rich in menhaden oil decreased the growth of human mammary carcinoma MX-1, increased its responsiveness to MC, and increased its susceptibility to endogenous and MC-induced oxidative stress, and increased the tumor activities of two enzymes proposed to be involved in the bioactivation of MC, that is, DT-diaphorase and xanthine oxidase. These findings support a role of these two enzymes in the bioactivating of MC and indicate that the type of dietary fat may be important in tumor response to therapy.
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PMID:Dietary menhaden oil enhances mitomycin C antitumor activity toward human mammary carcinoma MX-1. 856 32

Oxygen stress is well recognized to be a key step in the pathogenesis of ethanol-associated liver injury. Ethanol administration induces an increase in lipid peroxidation either by enhancing the production of oxygen-reactive species and/or by decreasing the level of endogenous antioxidants. Numerous experimental studies have emphasized the role of the ethanol-inducible cytochrome P-450 in the microsomes, as well as the molybdo-flavoenzymes xanthine oxidase in the cytosol. This review shows the putative role of ethanol-induced disturbances in iron metabolism in relation to iron as a prooxidant factor. Ethanol administration also affects the mitochondrial free radical generation. Although many previous studies suggest a role for active oxygens in ethanol-induced mitochondrial dysfunction in hepatocytes, the detailed mechanism of ethanol-induced oxidative stress on mitochondria remains to be clarified further. Studies of our laboratory using a confocal laser scanning microscopic system strongly suggest that active oxidants produced during ethanol metabolism modulate mitochondrial energy synthesis in isolated and cultured hepatocytes. In addition, our investigations implicate endogenous glutathione-glutathione peroxidase system and catalase as important antioxidants and cytoprotective machinery in the hepatocyte mitochondria exposed to ethanol. The fluorographic investigations using the confocal laser scanning microscopy may be useful to extend our knowledge and provide a new view about ethanol-associated oxidative stress and metabolic changes in hepatocytes.
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PMID:Ethanol-induced oxidative stress in the liver. 865 98

The protective effect of allopurinol, an inhibitor of the enzyme, xanthine oxidase, against the renal ischaemia-reperfusion of the rat was investigated. Rats were subjected to renal ischaemia by clamping of the left renal artery and vein for 45 min, and were then reperfused for 24 h; these animals were randomized to receive either saline (n = 10) or allopurinol (n = 10) at a dose of 50 mg/kg bolus intraperitoneally 5 min before reperfusion. The control group comprised seven healthy rats not exposed to ischaemia or reperfusion. The blood urea nitrogen and plasma creatinine levels were increased in the allopurinol group, but the increase was less than that in the placebo group, compared with the controls. The kidney glutathione level was significantly reduced in the placebo group but not in the allopurinol group compared with the controls. The glutathione peroxidase activity in the kidney tissues was reduced more than two-fold in the placebo group compared with the controls, but the reduction in glutathione peroxidase was considerably less in the allopurinol group. Renal tissue lactate dehydrogenase, aspartate amino-transferase, gamma-glutamyl transferase and alkaline phosphatase activities were reduced almost two-fold in the placebo group, but allopurinol treatment maintained these enzyme activities close to the control activities. These results provide evidence that allopurinol treatment may have beneficial effects on antioxidant defences against ischaemia-reperfusion injury of rat kidneys.
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PMID:Beneficial effects of allopurinol on glutathione levels and glutathione peroxidase activity in rat ischaemic acute renal failure. 867 98

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

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

For quantitative evaluation of lipid peroxidation after perinatal hypoxia in umbilical arterial cord blood samples from 109 healthy, acidotic, and asphyctic neonates with a gestational age ranging from 26 to 41 wk, the levels of aldehydic lipid peroxidation products malondialdehyde (MDA) and 4-hydroxynon-2-enal (HNE) were measured. Furthermore, the concentrations of oxidized and reduced glutathione (GSSH and GSH) and the purine compounds hypoxanthine and uric acid were determined. With increasing gestational age MDA and HNE levels increased. Furthermore, an increased level of GSH was also found. After perinatal hypoxia the concentrations of MDA and HNE rose distinctly (p < 0.001), reflecting sensitively the extent of in vivo lipid peroxidation. HNE is proposed to be a new parameter for quantitative evaluation of posthypoxic cellular damage in the perinatal period. HNE is a more specific parameter for estimation of lipid peroxidation processes in comparison with MDA. Additionally, HNE is cytotoxic and mutagenic at nanomolar concentrations. The increased levels of both MDA and HNE were accompanied by a strong decrease of GSH concentrations (p < 0.001), indicating the rapid consumption of GSH via a glutathione peroxidase reaction but additionally the high reactivity of HNE with sulfhydryl groups. During oxygen deficiency, increased levels of hypoxanthine (p < 0.01) and uric acid (p < 0.05) were due to the accelerated degradation of purine nucleotides. The rate of purine degradation including xanthine oxidase reactions characterizes the extent of an important radical source during oxygen deficiency, contributing to peroxidation of polyunsaturated fatty acids and the formation of peroxidation of polyunsaturated fatty acids and the formation of secondary aldehydic lipid peroxidation products.
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PMID:Increased levels of lipid peroxidation products malondialdehyde and 4-hydroxynonenal after perinatal hypoxia. 879 39

To prevent oxidative tissue damage induced by strenuous exercise in the liver and kidney superoxide dismutase derivative (SM-SOD), which circulated bound to albumin with a half-life of 6 h, was injected intraperitoneally into rats. Exhausting treadmill running caused a significant increase in the activities of xanthine oxidase (XO), and glutathione peroxidase (GPX) in addition to concentrations of thiobarbituric acid-reactive substances (TBARS) in hepatic tissue immediately after running. There was a definite increase in the immunoreactive content of mitochondrial superoxide dismutase (Mn-SOD) 1 day after the running. Meanwhile, the TBARS concentration in the kidney was markedly elevated 3 days after running. The activities of GPX, and catalase in the kidney increased significantly immediately and on days 1 and 3 following the test. The immunoreactive content of Mn-SOD also increased 1 day after running. The exercise induced no significant changes in immunoreactive Cu, Zn-SOD content in either tissue. The administration of SM-SOD provided effective protection against lipid peroxidation, and significantly attenuated the alterations in XO and all the anti-oxidant enzymes, measured. In summary, the present data would suggest that exhausting exercise may induce XO-derived oxidative damage in the liver, while the increase in lipid peroxidation in the kidney might be the result of washout-dependent accumulation of peroxidised metabolites. We found that the administration of SM-SOD provided excellent protection against exercise-induced oxidative stress in both liver and kidney.
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PMID:Superoxide dismutase derivative prevents oxidative damage in liver and kidney of rats induced by exhausting exercise. 882 Aug 84

Since the description of bronchopulmonary dysplasia (BPD) in premature infants, the supplemental oxygen administered has been suspect in the etiology of BPD. This has prompted studies on the effect of hyperoxia on lung growth in neonatal animals. So far, these have not led to a treatment which either prevents or mitigates BPD. Another approach to investigate the effect of hyperoxia on the immature lung is to use lung explants from 12-d gestation mouse fetuses. Exposing explants to different concentrations of oxygen for 48 h, we found that exposures to oxygen both below (10%) and above (35% or greater) normoxia adversely affected branching morphogenesis and growth. The effect was irreversible at exposures of 50% oxygen and greater. To determine the role of reactive oxygen species (ROS) in the effect of hyperoxia, antioxidants and inhibitors of ROS formation were added to the incubating explants, and their influence on reducing the adverse effect of 50% oxygen was assessed. The combination of CuZn superoxide dismutase (SOD) and catalase, manganese SOD, manganese-3-tetrakis(1-methyl-4-pyridyl)porphorin, a low molecular weight SOD mimetic, and to a lesser extent, deferoximine, an antioxidant and inhibitor of hydroxyl radical formation, were successful in reducing the effect of 50% oxygen on morphogenesis. Not successful were N-nitro-L-arginine methyl ester (an inhibitor of nitric oxide synthase); allopurinol (an inhibitor of xanthine oxidase); N-acetylcysteine and ebselen (a glutathione peroxidase mimetic); Trolox (a synthetic tocopherol); catalase, and CuZnSOD used alone. These results provide evidence that superoxide anion and possibly hydroxyl radical are the ROS most likely responsible for the growth effects of hyperoxia on mouse fetal lung morphogenesis.
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PMID:Oxygen toxicity to the developing lung of the mouse: role of reactive oxygen species. 882 70


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