Renal purine efflux and xanthine oxidase activity during experimental nephrosis in rats: Difference between puromycin aminonucleoside and adriamycin nephrosis

1990 ◽  
Vol 78 (3) ◽  
pp. 283-293 ◽  
Author(s):  
Fabrizio Ginevri ◽  
Rosanna Gusmano ◽  
Roberta Oleggini ◽  
Silvia Acerbo ◽  
Roberta Bertelli ◽  
...  
Keyword(s):  
Uric Acid ◽  
Free Radicals ◽  
Urinary Excretion ◽  
Xanthine Oxidase ◽  
Oxidase Activity ◽  
Xanthine Dehydrogenase ◽  
Renal Tissue ◽  
Puromycin Aminonucleoside ◽  
Oxidase System ◽  
Baseline Values

1. The hypothesis was tested that the renal xanthine oxidase system provides a source of oxygen free radicals in puromycin aminonucleoside and adriamycin experimental nephrosis by generating uric acid from hypoxanthine and xanthine. 2. The concentrations in renal tissue of the putative intermediary products of puromycin aminonucleoside metabolism, hypoxanthine and xanthine, and of their precursors, adenosine and inosine, were lower in rats treated with puromycin aminonucleoside than in normal controls, whereas concentrations of the metabolites were normal after adriamycin intoxication. Their daily urinary excretion was lower in the 24 h after puromycin amino-nucleoside administration compared with the baseline values and returned to near normal levels within 5 days. After adriamycin the 24 h urinary excretion of xanthine and uric acid was double the baseline levels (P <0.001). 3. When equimolar amounts of hypoxanthine were injected instead of puromycin aminonucleoside, the concentration of all bases increased slightly in renal tissue and their urinary efflux was double the baseline level: allantoin, uric acid, the unmodified nucleotide and xanthine were the most represented compounds in urine. 4. The enzymatic activities relative to xanthine oxidase (EC 1.1.3.22) and xanthine dehydrogenase (EC 1.1.1.204) in renal tissues were unchanged 1 day after puromycin aminonucleoside or hypoxanthine intoxication and only moderately increased in both groups at 13 days (the time of appearance of heavy proteinuria in the puromycin aminonucleoside-treated group). In contrast, xanthine oxidase and xanthine dehydrogenase activities were higher in adriamycin-treated rats at 1 and 15 days after the treatment (P <0.001). 5. Feeding rats with normoprotein diets containing tungsten induced a marked and constant decrease of renal xanthine oxidase and xanthine dehydrogenase activities to 20% of the baseline values in both puromycin amino-nucleoside- and adriamycin-treated rats. Inhibition of renal xanthine oxidase and xanthine dehydrogenase activities by tungsten was associated with a marked reduction (P <0.001) of proteinuria in adriamycin-treated rats and the same occurred with allopurinol, a specific inhibitor of xanthine oxidase activity. In contrast, tungsten treatment did not reduce the proteinuria associated with puromycin aminonucleoside, which reached a maximum 13 days after puromycin aminonucleoside intoxication. Hypoxanthine-treated rats were normoproteinuric after 2 months of observation. 6. These data demonstrate an activation of renal xanthine oxidase and xanthine dehydrogenase after adriamycin intoxication which is relevant to the induction of proteinuria. They also argue against the involvement of the renal xanthine oxidase system as a source of free radicals in puromycin aminonucleoside nephrosis and suggest that the nucleotide cycle is not a normal route for puromycin aminonucleoside degradation. Other metabolic pathways for free radical generation from puromycin aminonucleoside must be considered.

Changes in xanthine oxidase in ischemic rat brain

1989 ◽  
Vol 71 (3) ◽  
pp. 417-420 ◽  
Author(s):  
Yuji Kinuta ◽  
Mieko Kimura ◽  
Yoshinori Itokawa ◽  
Masatsune Ishikawa ◽  
Haruhiko Kikuchi
Keyword(s):  
Uric Acid ◽  
Free Radicals ◽  
Cerebral Ischemia ◽  
Xanthine Oxidase ◽  
Rat Brain ◽  
Oxidase Activity ◽  
High Performance ◽  
Vessel Occlusion ◽  
Content Type ◽  
Xanthine Oxidase Activity

✓ Xanthine oxidase activity in the rat brain was measured by means of high-performance liquid chromatography with electrochemical detection of uric acid. Cerebral ischemia was produced by a four-vessel occlusion method. In the control rat, the enzyme activity was 0.87 ± 0.13 nmol/gm wet weight/min at 25°C (mean ± standard deviation), of which 92.4% was associated with the nicotinamide adenine dinucleotide (NAD)-dependent dehydrogenase form and only 7.6% with the oxygen-dependent superoxide-producing oxidase form. However, the ratio of the latter form increased to 43.7% after 30 minutes of global ischemia, despite the total xanthine oxidase activity remaining the same. Thus, it was revealed that uric acid can be synthesized in the rat brain and that cerebral ischemia induced the conversion of xanthine oxidase from an NAD-dependent dehydrogenase to an oxygen-dependent superoxide-producing oxidase. Although the xanthine oxidase pathway has been proposed as a source of oxygen-derived free radicals in various ischemic organs other than brain, the results of the present study suggest the involvement of the oxygen free radicals generated from this pathway in the pathogenesis of the ischemic injury of the rat brain.

scholarly journals Bactericidal activity of a superoxide anion-generating system. A model for the polymorphonuclear leukocyte.

1979 ◽  
Vol 149 (1) ◽  
pp. 27-39 ◽  
Author(s):  
H Rosen ◽  
S J Klebanoff
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Bactericidal Activity ◽  
Parent Strain ◽  
Carotenoid Pigments ◽  
Bacterial Killing ◽  
Oxidase System ◽  
System A ◽  
Presence And Absence ◽  
Generating System

The acetaldehyde-xanthine oxidase system in the presence and absence of myeloperoxidase (MPO) and chloride has been employed as a model of the oxygen-dependent antimicrobial systems of the PMN. The unsupplemented xanthine oxidase system was bactericidal at relatively high acetaldehyde concentrations. The bactericidal activity was inhibited by superoxide dismutase (SOD), catalase, the hydroxyl radical (OH.) scavengers, mannitol and benzoate, the singlet oxygen (1O2) quenchers, azide, histidine, and 1,4-diazabicyclo[2,2,2]octane (DABCO) and by the purines, xanthine, hypoxanthine, and uric acid. The latter effect may account for the relatively weak bactericidal activity of the xanthine oxidase system when purines are employed as substrate. A white, carotenoid-negative mutant strain of Sarcina lutea was more susceptible to the acetaldehyde-xanthine oxidase system than was the yellow, carotenoid-positive parent strain. Carotenoid pigments are potent 1O2 quenchers. The xanthine oxidase system catalyzes the conversion of 2,5-diphenylfuran to cis-dibenzoylethylene, a reaction which can occur by a 1O2 mechanism. This conversion is inhibited by SOD, catalase, azide, histidine, DABCO, xanthine, hypoxanthine, and uric acid but is only slightly inhibited by mannitol and benzoate. The addition of MPO and chloride to the acetaldehyde-xanthine oxidase system greatly increases bactericidal activity; the minimal effective acetaldehyde concentration is decreased 100-fold and the rate and extent of bacterial killing is increased. The bactericidal activity of the MPO-supplemented system is inhibited by catalase, benzoate, azide, DABCO, and histidine but not by SOD or mannitol. Thus, the acetaldehyde-xanthine oxidase system which like phagocytosing PMNs generates superoxide (O.2-) and hydrogen peroxide, is bactericidal both in the presence and absence of MPO and chloride. The MPO-supplemented system is considerably more potent; however, when MPO is absent, bactericidal activity is observed which may be mediated by the interaction of H2O2 and O.2- to form OH. and 1O2.

Hypouricemic Effects of Phenylpropanoid Glycosides Acteoside ofScrophularia ningpoensison Serum Uric Acid Levels in Potassium Oxonate-Pretreated Mice

2008 ◽  
Vol 36 (01) ◽  
pp. 149-157 ◽  
Author(s):  
Cai Guo Huang ◽  
Yan Jun Shang ◽  
Jun Zhang ◽  
Jian Rong Zhang ◽  
Wen Jie Li ◽  
...  
Keyword(s):  
Uric Acid ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Xanthine Oxidase ◽  
Serum Uric Acid ◽  
Mouse Liver ◽  
Xanthine Dehydrogenase ◽  
Phenylpropanoid Glycoside ◽  
Phenylpropanoid Glycosides ◽  
Potassium Oxonate

Phenylpropanoid glycoside acteoside was extracted from the traditional Chinese medicine Scrophularia ningpoenis Hemsl. In the present study, we investigated the effects of acteoside administration on serum uric acid levels in mice rendered hyperuricemic with the uricase inhibitor potassium oxonate. When administered orally for 3 days at doses of 50, 100 and 150 mg/kg, acteoside reduced serum uric acid levels by 15.2, 23.8 and 33.1%, respectively, relative to vehicle-treated hyperuricemic mice. Importantly, in non-hyperuricemic mice, the serum uric acid levels were not affected by acetoside treatment. Acteoside also inhibited mouse liver xanthine dehydrogenase XDH and xanthine oxidase XO activity at all three doses. These results suggest that the hypouricemic action of acteoside may be attributable to its inhibition of XDH/XO activity.

Effects of Onion on Serum Uric Acid Levels and Hepatic Xanthine Dehydrogenase/Xanthine Oxidase Activities in Hyperuricemic Rats

2008 ◽  
Vol 11 (14) ◽  
pp. 1779-1784 ◽  
Author(s):  
Fatemeh Haidari ◽  
Mohammad Reza Rashidi ◽  
Seid Ali Keshavarz ◽  
Soltan Ali Mahboob ◽  
Mohammad Reza Eshraghian ◽  
...  
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Serum Uric Acid ◽  
Xanthine Dehydrogenase

Xanthine oxidase is not a major source of free radicals in focal cerebral ischemia

1991 ◽  
Vol 260 (2) ◽  
pp. H563-H568 ◽  
Author(s):  
A. L. Betz ◽  
J. Randall ◽  
D. Martz
Keyword(s):  
Uric Acid ◽  
Free Radicals ◽  
Cerebral Ischemia ◽  
Xanthine Oxidase ◽  
Brain Edema ◽  
Focal Cerebral Ischemia ◽  
Total Activity ◽  
Brain Regions ◽  
Free Radical Scavengers ◽  
Edema Formation

Xanthine oxidase (XO) has been proposed as an important source of free radicals during ischemia. This enzyme normally exists as a dehydrogenase (XD), but it is converted to XO in some ischemic tissues. Recently, treatment of animals with the XD and XO inhibitor allopurinol or with free radical scavengers before cerebral ischemia has been shown to reduce brain injury. Therefore, we studied conversion of XD to XO in three ischemic and nonischemic brain regions during focal cerebral ischemia resulting from permanent occlusion of the middle cerebral artery (MCAO) in anesthetized rats. In nonischemic brain, 16-22% of the enzyme was in the XO form. After 24 h of ischemia this value was not significantly different (10-15%). Neither the total activity of XO nor that of XD changed, indicating that there was no irreversible conversion of XD to XO. To further explore the possible role of XO, we examined the effect of various doses of allopurinol (5, 20, or 100 mg/kg given 1 h before MCAO or 100 mg/kg given 48, 24, and 1 h before MCAO) on uric acid accumulation, brain edema formation, and cerebral blood flow (CBF) 24 h after MCAO. All but the lowest dose of allopurinol greatly reduced the appearance of uric acid in the ischemic brain; however, only the highest dose of allopurinol had any beneficial effect on brain edema. This reduction in brain edema occurred without a significant improvement in CBF. Thus XO is probably not an important source of free radicals in this model of focal cerebral ischemia.

scholarly journals Xanthine Oxidase of the Clothes Moth, Tineola Bisselliella, and Some Other Insects

1955 ◽  
Vol 8 (3) ◽  
pp. 369 ◽  
Author(s):  
H Irzykiewicz
Keyword(s):  
Methylene Blue ◽  
Uric Acid ◽  
Toxic Effect ◽  
Xanthine Oxidase ◽  
Oxidase Activity ◽  
Acid Production ◽  
Fat Body ◽  
Optimum Concentration ◽  
Optimum Ph ◽  
Wet Weight

Xanthine oxidase activity in Tineola larvae averages 200� /!moles of uric acid per g whole larva (wet weight) per hr and in Tenebrio, Lucilia, Anthrenocerus, Ephestia, and Anthrenus larvae activity ranges between 13�4 and 1�3. The optimum pH for Tineola xanthine oxidase lies between pH 7�7 and 8� 0, and the optimum concentration of xanthine is at or below 1�3 X 10-3M. Methylene blue in concentrations up to 5�3 X 1O-3M has no toxic effect on this enzyme, and the lower concentrations of methylene blue have a limiting effect. Cyanide and 6-pteridyl aldehyde inhibit Tineola xanthine oxidase. The insect xanthine oxidases are demonstrated to be dehydrogenases. DPN, and pyruvate and DPN together, stimulate uric acid production by Tineola xanthine oxidase in the absence of methylene blue. In Tenebrio larvae there is a higher concentration of xanthine oxidase in the midgut and fat-body than in the remaining tissues.

scholarly journals The superoxide-dependent transfer of iron from ferritin to transferrin and lactoferrin

1988 ◽  
Vol 256 (3) ◽  
pp. 923-928 ◽  
Author(s):  
H P Monteiro ◽  
C C Winterbourn
Keyword(s):  
Lipid Peroxidation ◽  
Free Radicals ◽  
Xanthine Oxidase ◽  
Binding Protein ◽  
Gel Filtration ◽  
Iron Binding ◽  
Oxidase System ◽  
Oxidative Reactions ◽  
Phospholipid Liposomes ◽  
Iron Binding Protein

By the use of gel filtration and [59Fe]ferritin, apotransferrin and apolactoferrin were shown to take up iron released from ferritin by superoxide generated by hypoxanthine and xanthine oxidase. Apotransferrin also inhibited uptake of released iron by ferrozine. Ferritin and the xanthine oxidase system induced lipid peroxidation in phospholipid liposomes. This peroxidation was inhibited by apotransferrin or apolactoferrin. Thus, although superoxide and other free radicals can release iron from ferritin, either iron-binding protein, if present, should take up this iron and prevent its catalysing subsequent oxidative reactions.

Decreased hepatosplanchnic antioxidant uptake during hepatic ischaemia/reperfusion in patients undergoing liver resection

2008 ◽  
Vol 114 (8) ◽  
pp. 553-560 ◽  
Author(s):  
Marcel C. G. van de POLL ◽  
Cornelis H. C. Dejong ◽  
Marc A. J. G. Fischer ◽  
Aalt Bast ◽  
Ger H. Koek
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Liver Resection ◽  
Xanthine Oxidase ◽  
Oxidase Activity ◽  
Ischaemic Preconditioning ◽  
Xanthine Oxidase Activity ◽  
Ischaemia Reperfusion ◽  
Plasma Antioxidant Capacity ◽  
Plasma Antioxidant

Oxidative stress mediates cell injury during ischaemia/reperfusion. On the other hand, experimental findings suggest that ROS (reactive oxygen species) induce processes leading to ischaemic preconditioning. The extent and source of oxidative stress and its effect on antioxidant status in the human liver during intermittent ischaemia and reperfusion remains ill-defined. Therefore the aim of the present study was to investigate the occurrence of oxidative stress in humans undergoing liver resection. Liver biopsies, and arterial and hepatic venous blood samples were taken from ten patients undergoing hepatectomy with an intermittent Pringle manoeuvre. Plasma MDA (malondialdehyde) and hepatic GSSG levels were measured as markers of oxidative stress and plasma uric acid as a marker of xanthine oxidase activity. In addition, changes in hepatosplanchnic consumption of plasma antioxidants and hepatic levels of carotenoids and glutathione (GSH) were measured. After ischaemia, hepatosplanchnic release of MDA and increased hepatic GSSG levels were found. This was accompanied by the release of uric acid, reflecting xanthine oxidase activity. During reperfusion, ongoing oxidative stress was observed by further increases in hepatic GSSG content and hepatosplanchnic MDA release. Uric acid release was minimal during reperfusion. A gradual decrease in plasma antioxidant capacity and net hepatosplanchnic antioxidant uptake was observed upon prolonged cumulative ischaemia. Oxidative stress occurs during hepatic ischaemia in man mainly due to xanthine oxidase activity. Interestingly, the gradual decline in plasma antioxidant capacity and net hepatosplanchnic antioxidant uptake during prolonged cumulative ischaemia, preserved both hydrophilic and lipophilic hepatic antioxidant levels. Decreasing plasma levels and net hepatosplanchnic uptake of plasma antioxidants may warrant antioxidant supplementation, although it should be clarified to what extent limitation of oxidative stress compromises ROS-dependent pathways of ischaemic preconditioning.

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