Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.17.3.2 (xanthine oxidase)
8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypothesis that posthypoxic renal injury is mediated by xanthine oxidase-derived oxygen free radical production was tested in an in vitro model of rat proximal tubule epithelial cells in primary culture subjected to 60 min of hypoxia and 30 min of reoxygenation. Hypoxia-reoxygenation-induced injury, measured as lactate dehydrogenase (LDH) release, was 54.0 +/- 7.1%. Inhibition of xanthine oxidase by 10(-4) M allopurinol attenuated injury (LDH release = 35.5 +/- 3.7%; P less than 0.01). Oxypurinol was similarly effective. Alternatively, cells were treated with 50 or 100 microM tungsten to inactivate xanthine oxidase. Tungsten prevented hypoxia-reoxygenation-induced superoxide radical production (basal = 97 +/- 8, hypoxia-reoxygenation = 172 +/- 12, and plus tungsten = 73 +/- 8 nmol/micrograms protein) and attenuated hypoxia-reoxygenation-induced injury (LDH release: basal = 18.8 +/- 3.0%, hypoxia-reoxygenation = 62.0 +/- 4.8%, plus 50 microM tungsten = 24.8 +/- 5.0%, and plus 100 microM tungsten = 6.0 +/- 0.7%). In addition, hypoxia and reoxygenation increased the ratio of xanthine oxidase to total activity (xanthine oxidase + xanthine dehydrogenase) from 73 to 100%. Therefore xanthine oxidase was responsible for hypoxia-reoxygenation-induced superoxide radical formation and hypoxia-reoxygenation-induced injury. Xanthine oxidase is likely to be the major source of oxygen free radicals during renal ischemia and reperfusion.
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PMID:Xanthine oxidase produces O2-. in posthypoxic injury of renal epithelial cells. 132 7

Escherichia coli is the most frequent cause of pyelonephritis. Its possible virulence factors include the ability to adhere and colonize the urinary tract, an important initiating factor in all urinary tract infections (UTIs). The importance of P fimbriae in this adhesion is stressed and the evidence for its importance in pyelonephritis is presented in epidemiologic studies of patients, as well as in animal studies. It appears that both host receptor density and the nonsecretor state is responsible for susceptibility to urinary tract infection. Vesicoureteral reflux can be responsible for ascending upper tract infection, but infection with P-fimbriated E coli may lead to ascending pyelonephritis without reflux because of the paralytic effect of lipid A on ureteral peristaltic activity. Renal ischemia leads to renal damage following infection by reperfusion damage due to the release of superoxide. Experimentally, this ischemic damage can be prevented by allopurinol, a xanthine oxidase inhibitor. The acute inflammatory response can produce renal damage because of the respiratory burst of phagocytosis, which while killing phagocytosed bacteria also damages renal tubules. An amelioration of the inflammatory response by treatment with superoxide dismutase or corticosteroids has been shown to modulate renal damage. Vaccination with P fimbriae has been shown experimentally to prevent the initiation of the disease. However, since vaccines are not clinically available, the clinical and animal studies on therapy of acute disease are stressed. Acute pyelonephritis during the first 3 years of life more often produced the renal damage that could lead to end-stage renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Etiology and pathophysiology of pyelonephritis. 167 Sep 5

Renal ischemia injures the renal tubular cell by disrupting the vital cellular metabolic machinery. Further cell damage is caused by restoration of blood flow when oxygen free radicals are produced. Cellular sources of oxygen free radicals include the electron transport chain, the microsomal electron transport chain, oxidant enzymes (xanthine oxidase, cyclo-oxygenase), phagocytes, and cellular auto-oxidation of Fe2+ and epinephrine. Oxygen radicals cause lipid peroxidation of cell and organelle membranes, disrupting the structural integrity and capacity for cell transport and energy production. Studies in models of acute renal failure have yielded convincing evidence that oxygen free radical production occurs during ischemia/reperfusion. More than a dozen reports have demonstrated the ability of exogenous antioxidants to ameliorate renal injury in vivo. Direct demonstration of increased oxygen free radical production during reoxygenation following hypoxia has been shown in cultured renal epithelial cells. Oxygen free radicals also play a role in toxic acute renal failure. The therapeutic usefulness of free radical scavengers remains to be tested.
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PMID:Oxygen free radicals in acute renal failure. 175 21

Oxygen metabolites formed during reperfusion of ischemic kidneys prevent recovery of renal function after short periods of renal ischemia. Xanthine oxidase has been proposed as a source of toxic oxygen metabolites during reperfusion of ischemic kidneys. To determine whether the enzyme is converted from the non-oxygen metabolite-producing dehydrogenase (type D) to the oxygen metabolite-producing oxidase (type O), we measured type D and type O (total, reversible, and irreversible) xanthine oxidase in renal cortical homogenates after 30 min of ischemia in vivo and 60 min of reperfusion by the isolated perfused kidney technique. Total enzyme activity (type D plus type O) was not altered by ischemia or reperfusion. Compared with nonischemic conditions, ischemia increased total type O (53 +/- 5 vs. 21 +/- 3%, P less than 0.01) and reversible type O (15.4 +/- 1.5 vs. 2.1 +/- 1.4 U/g) xanthine oxidase activities. Reperfusion further increased total type O (82 +/- 3%) and reversible type O (27.7 +/- 3.3 U/g, both P less than 0.01 vs. nonischemic perfusions) xanthine oxidase activities. To determine the physiological role of xanthine oxidase in renal ischemia, we depleted rats of xanthine oxidase by feeding tungsten. After 4 wk of tungsten, renal xanthine oxidase levels were reduced by greater than 90% and renal function was markedly improved during reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of xanthine oxidase in ischemia/reperfusion injury. 231 73

Previous studies show that chronic pyelonephritis and end stage renal disease may follow acute pyelonephritis in children and adolescents when improperly or inadequately treated. Our study shows that there is a significant decrease in renal function following untreated acute bacterial pyelonephritis due to nephron loss. The acute inflammatory response is responsible for much of the renal damage, although damage from renal ischemia is an additional significant factor. The present study used a combination of an antibiotic and a xanthine oxidase inhibitor (allopurinol) as compared to antibiotic therapy alone begun 72 hours after infection. Both were successful in eradicating the infection rapidly, but did not entirely prevent renal damage. Treatment prior to 72 hours thus is important. It appears that the combined treatment, designed to eradicate the bacteria as well as reduce the post-ischemic reperfusion damage and the phagocytic burst of phagocytosis is ideal, as this combined treatment was effective in preventing almost all renal damage and loss of renal function.
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PMID:Treatment of experimental pyelonephritis in the monkey. 240 97

It is known that renal ischemia enhances the production of adenosine, which is further metabolized by xanthine oxidase, and that the inhibition of this metabolizing enzyme by allopurinol ameliorates the consequences of renal ischemia. This study was undertaken to define the effect of allopurinol on the renal responses to adenosine. It was found that 5 minutes of intrarenal infusion of adenosine in control dogs produced a typical biphasic response characterized by an initial vasoconstriction, decreasing renal blood flow by 46.3% +/- 6.0%, followed by vasodilation, increasing renal blood flow by 8.5% +/- 3.6% above the control levels. Adenosine infusion was also accompanied by a significant reduction of plasma renin activity, from 8.4 +/- 0.6 ng/ml/hour to 3.8 +/- 0.4 ng/ml/hour. The administration of an intravenous infusion of 50 mg allopurinol did not alter the vasoconstrictor phase of adenosine--the average decrease was 41.1% +/- 3.3%; however, it prevented much of the vasodilation because renal blood flow over the 5 minutes remained 17.9% +/- 5.0% less than the levels recorded before adenosine infusion. Allopurinol also prevented the decrease of plasma renin activity, for which the average values recorded before and after adenosine were 9.6 +/- 0.6 ng/ml/hour and 8.2 +/- 0.6 ng/ml/hour, respectively. The results of this study indicate that allopurinol exerts specific effects on the vasodilatory component of adenosine and prevents the adenosine-suppressive effect on the renin-angiotensin system.
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PMID:Effect of allopurinol on the renovascular responses to adenosine. 351 11

Superoxide anion free radical (O2-.) has been implicated in the pathogenesis of tissue injury consequent to ischemia/reperfusion in several different organs, including heart and bowel. Superoxide dismutase (SOD), an enzyme free radical scavenger specific for O2-., has been used successfully to protect these organs from structural damage during reoxygenation of ischemic tissue. It has been suggested that the catalytic action of xanthine oxidase in injured tissue is an important source of O2-. during reoxygenation. In order to evaluate the potential of SOD to protect against kidney damage resulting from transient ischemia followed by reperfusion with oxygenated blood, a model of warm renal ischemia was studied. LBNF1 rats underwent right nephrectomy and occlusion of the left renal artery for 45 minutes. Survival in the group of ischemic untreated rats (N = 30) was 56% at 7 days and serum creatinine was greatly elevated (p less than 0.01) in rats remaining alive over the full 7-day period. In strong contrast to these results, all of the animals treated with SOD before reperfusion (N = 18) were alive after 7 days similar to sham operated control rats (N = 8). Serum creatinine in the SOD treated rats was significantly elevated only to postoperative day 3 and thereafter returned to normal. Rats treated with inactive SOD (N = 4) or SOD before ischemia (N = 4) had decreased survival rates compared to ischemic untreated animals and prolonged elevation of serum creatinine. When the ischemia time was extended to 60 minutes, only 19% of the untreated animals (N = 16) survived at 7 days whereas nearly 60% of the SOD-treated animals survived (N = 19). Serum creatinine was greatly elevated during the full 7-day observation period in all surviving rats in the untreated ischemic group, whereas serum creatinine returned to normal (p less than 0.05) after 4 days in the surviving rats treated with SOD. To test whether the action of xanthine oxidase contributed to the kidney damage after reoxygenation, 45 min. ischemic rat kidneys were treated with allopurinol. All of the animals treated with allopurinol (N = 12) were alive at 7 days. Serum creatinine values returned to normal after the episode of ischemia and reperfusion but more slowly than after SOD treatment. Histologic evaluation of kidney tissue taken from animals after ischemia alone showed extensive renal tubular damage, which was essentially absent in kidneys from SOD-treated animals.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Oxygen free radical induced damage in kidneys subjected to warm ischemia and reperfusion. Protective effect of superoxide dismutase. 384 Mar 48

During renal ischemia, ATP is degraded to hypoxanthine. When xanthine oxidase converts hypoxanthine to xanthine in the presence of molecular oxygen, superoxide radical (O-2) is generated. We studied the role of O-2 and its reduction product OH X in mediating renal injury after ischemia. Male Sprague-Dawley rats underwent right nephrectomy followed by 60 min of occlusion of the left renal artery. The O-2 scavenger superoxide dismutase (SOD) was given 8 min before clamping and before release of the renal artery clamp. Control rats received 5% dextrose instead. Plasma creatinine was lower in SOD treated rats: 1.5, 1.0, and 0.8 mg/dl vs. 2.5, 2.5, and 2.1 mg/dl at 24, 48, and 72 h postischemia. 24 h after ischemia inulin clearance was higher in SOD treated rats than in controls (399 vs. 185 microliter/min). Renal blood flow, measured after ischemia plus 15 min of reflow, was also greater in SOD treated than in control rats. Furthermore, tubular injury, judged histologically in perfusion fixed specimens, was less in SOD treated rats. Rats given SOD inactivated by prior incubation with diethyldithiocarbamate had plasma creatinine values no different from those of control rats. The OH X scavenger dimethylthiourea (DMTU) was given before renal artery occlusion. DMTU treated rats had lower plasma creatinine than did controls: 1.7, 1.7, and 1.3 mg/dl vs. 3.2, 2.2, and 2.4 mg/dl at 24, 48, and 72 h postischemia. Neither SOD nor DMTU caused an increase in renal blood flow, urine flow rate, or solute excretion in normal rats. The xanthine oxidase inhibitor allopurinol was given before ischemia to prevent the generation of oxygen free radicals. Plasma creatinine was lower in allopurinol treated rats: 2.7, 2.2, and 1.4 mg/dl vs. 3.6, 3.5, and 2.3 mg/dl at 24, 48, and 72 h postischemia. Catalase treatment did not protect against renal ischemia, perhaps because its large size limits glomerular filtration and access to the tubular lumen. Superoxide-mediated lipid peroxidation was studied after renal ischemia. 60 min of ischemia did not increase the renal content of the lipid peroxide malondialdehyde, whereas ischemia plus 15 min reflow resulted in a large increase in kidney lipid peroxides. Treatment with SOD before renal ischemia prevented the reflow-induced increase in lipid peroxidation in renal cortical mitochondria but not in crude cortical homogenates. In summary, the oxygen free radical scavengers SOD and DMTU, and allopurinol, which inhibits free radical generation, protected renal function after ischemia. Reperfusion after ischemia resulted in lipid peroxidation; SOD decreased lipid peroxidation in cortical mitochondria after renal ischemia and reflow. We concluded that restoration of oxygen supply to ischemic kidney results in the production of oxygen free radicals, which causes renal injury by lipid peroxidation.
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PMID:Oxygen free radicals in ischemic acute renal failure in the rat. 643 91

There is considerable evidence suggesting that reactive oxygen species (ROS) are implicated in the pathogenesis of ischemic, toxic, and immunologically-mediated renal injury. In experimental renal ischemia, ROS sources include the electron transport chain, oxidant enzymes (xanthine oxidase), phagocytes, and auto-oxidation of epinephrine. ROS cause lipid peroxidation of cell and organelle membranes and, hence, disruption of the structural integrity and capacity for cell transport and energy production, especially in the proximal tubule segment. In experimental immune glomerulonephritis, ROS are generated by both infiltrating blood-borne cells (polymorphonuclear leukocytes and monocytes) and resident glomerular cells, mainly mesangial cells. Their formation results in morphologic lesions and in modifications of glomerular permeability to proteins through activation of proteases and reduction of proteoglycan synthesis. Additionally, they promote a reduction in glomerular blood flow and glomerular filtration rate through liberation of vasoconstrictory bioactive lipids (prostaglandins, thromboxane, and platelet activating factor) and, possibly, inactivation of relaxing nitric oxide. Further studies are needed to address the role of ROS in human glomerular diseases.
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PMID:Involvement of reactive oxygen species in kidney damage. 822 Oct 27

Oxygen-based free radicals produced by the enzyme xanthine oxidase may be involved in postischemic reperfusion injury. To determine whether oxypurinol, a xanthine oxidase inhibitor and the major metabolite of allopurinol, attenuates renal ischemic reperfusion injury, and, if so, to determine its most effective dose, oxypurinol 2.5, 5, 10 or 20 mg/kg BW was infused 20 min prior to 20 min of complete renal ischemia in uniephrectomized rats. Animals treated with 5 mg/kg BW oxypurinol had significantly higher creatinine clearances on the first and second days postischemia than did untreated animals. In other animals given either buffered saline or oxypurinol at 5 mg/kg BW i.v. 20 min before ischemia, the inulin clearance (CIn) returned to near-control values within 1 h after ischemia. At 24 h there was a secondary decline in the CIn in animals receiving buffered saline, whereas in the animals treated with oxypurinol, this decline was less evident. In animals given oxypurinol at 5 mg/kg BW 40 min after ischemia, the CIn was significantly greater than in those receiving buffered saline. No changes in renal blood flow or renal vascular resistance were observed, suggesting that the effect of oxypurinol was not hemodynamically mediated. Analysis of plasma hypoxanthine, xanthine, uric acid and oxypurinol levels by high-pressure liquid chromatography revealed that in the absence of oxypurinol, a significant increase in uric acid production occurred between 20 and 170 min after the period of ischemia. In the presence of oxypurinol, there was a marked reduction in the rate of production of uric acid for the first 3 h postischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of oxypurinol on renal reperfusion injury in the rat. 844 35


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