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)

The role of O2 free radicals in the reduction of sarcolemmal Na+-K+-ATPase, which occurs during reperfusion of ischemic heart, was examined in isolated guinea pig heart using exogenous scavengers of O2 radicals and an inhibitor of xanthine oxidase. Ischemia and reperfusion reduced Na+-K+-ATPase activity and specific [3H]ouabain binding to the enzyme in ventricular muscle homogenates and also markedly lowered sodium pump activity estimated from ouabain-sensitive 86Rb+ uptake by ventricular muscle slices. These effects of ischemia and reperfusion were prevented to various degrees by O2-radical scavengers, such as superoxide dismutase, catalase, dimethyl-sulfoxide, histidine, or vitamin E or by the xanthine oxidase inhibitor, allopurinol. The degree of protection afforded by these agents paralleled that of reduction in enhanced lipid peroxidation of myocardial tissue as estimated from malondialdehyde production. These results strongly suggest that O2 radicals play a crucial role in the injury to sarcolemmal Na+-K+-ATPase during reperfusion of ischemic heart.
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PMID:O2 free radicals: cause of ischemia-reperfusion injury to cardiac Na+-K+-ATPase. 302 76

The anti-oxidant efficacy, in vitro, of the gold compounds auranofin (AF) and gold sodium thiomalate (GST) was examined by studying their effects on the generation of reactive oxygen species (ROS) using zymosan-stimulated polymorphonuclear leukocytes (PMNs) and a cell-free, xanthine-xanthine oxidase system. The oxygen species investigated were the superoxide radical anion (O2-), hydrogen peroxide (H2O2) and the hydroxyl radical (OH.). AF had an inhibitory effect on ROS production by PMNs. In particular, OH. generation was significantly suppressed in a dose-dependent fashion. AF did not inhibit ROS production in the cell-free system. GST produced only a small degree of inhibition at higher concentrations. These findings suggest that AF may play an important role in the inhibition of respiratory bursts and the generation of inflammatory reaction products. Since the products of the respiratory burst, especially potent oxidants such as OH. and H2O2, are thought to be important inflammatory mediators, it is postulated that the blockade of toxic ROS generation by AF affects rheumatoid as well as dermatological inflammation and tissue damage.
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PMID:Anti-oxidant effects of gold compounds. 302 64

The effects of allopurinol pretreatment (1 mg/ml in the drinking water for 7 days at an estimated daily dose of 75 mg/kg) on biochemical and chemical changes occurring following left circumflex coronary artery ligation (40 min) and reperfusion (60 min) were examined in pentobarbital-anesthetized rabbits. During the ischemic phase, allopurinol pretreatment provided significant preservation of cellular ATP levels and of mitochondrial ATP generation as compared with untreated animals (P less than 0.05). During the reperfusion phase, allopurinol pretreatment significantly prevented the decrease in left ventricular pressure, sodium and calcium accumulation and decreases in sarcolemmal Na+,K+-stimulated and sarcoplasmic reticulum K+,Ca2+-stimulated ATPase activities as compared with untreated animals (P less than 0.05). In contrast, the decrease in mitochondrial (azide-sensitive) ATPase during ischemia and the partial recovery during reperfusion were unaffected by allopurinol pretreatment. Our results indicate that the myocardial protective effects of allopurinol may differ mechanistically in the ischemic and reperfusion phases of injury. The fact that rabbit hearts do not contain detectable xanthine oxidase activity would seem to preclude an obligatory role of this enzyme both in the generation of myocardial ischemic/reperfusion injury and in the protective actions of allopurinol.
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PMID:Effects of allopurinol on myocardial ischemic injury induced by coronary artery ligation and reperfusion. 303 15

Acridine dyes, fluorescein and lucifer yellow CH are fluorescent photosensitizers used experimentally to selectively stain and photodynamically destroy eukaryotic cells and subcellular structures. We have determined that the mechanism of light- and oxygen-dependent inactivation of E. coli by these dyes involves oxygen radicals and hydrogen peroxide. All of the dyes oxidized NAD(P)H+ under illumination. Superoxide (O2), detected as the superoxide dismutase (SOD)-inhibitable reduction of ferricytochrome c, was a major product of the dye sensitized photooxidation. Cationic acridine dyes penetrated the membranes of E. coli and were photoreduced intracellularly. Reduced dyes diffused back into the medium and mediated the reduction of extracellular ferricytochrome c. The anionic dyes fluorescein and lucifer yellow CH were unable to mediate extracellular cytochrome c reduction, indicating that these dyes were impermeable to the E. coli membrane. Acridine dyes, when illuminated, inhibited the growth of E. coli in a rich medium, and induced the synthesis of SOD. Fluorescein and lucifer yellow CH did not inhibit growth or induce SOD synthesis because they were unable to enter the cells. Superoxide (O2) and hydrogen peroxide (H2O2), generated by the enzyme xanthine oxidase were toxic to E. coli B. Inactivation by xanthine oxidase was partially inhibited by exogenous SOD and completely inhibited by exogenous catalase or SOD plus catalase. Similarly, exogenous SOD plus catalase protected against inactivation by acridines and fluorescein-NADH or lucifer yellow CH-NADH mixtures. Prior induction of superoxide dismutase and catalase in E. coli B significantly protected cells against a subsequent challenge by illuminated acridine dyes. SOD and catalases preinduction combined with additions of exogenous SOD and catalase completely protected E. coli B against photodynamic inactivation by acridine yellow. The hydroxyl radical scavengers, dimethyl sulfoxide, sodium benzoate and thiourea, protected E. coli B against photodynamic inactivation by acridine orange. The results implicate O2, H2O2, and the hydroxyl radical (OH) as underlying molecular agents of the phototoxicity mediated by acridine orange, acridine yellow, fluorescein and lucifer yellow CH.
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PMID:Oxygen radicals mediate cell inactivation by acridine dyes, fluorescein, and lucifer yellow CH. 303 47

Experiments were designed to determine the role of oxygen-derived free radicals in modulating contractions of vascular smooth muscle and endothelium-mediated relaxations to acetylcholine. The effects of generating or scavenging these radicals were studied in rings of canine coronary arteries suspended for isometric tension recording. Xanthine oxidase plus xanthine caused relaxations, which were greater in rings with endothelium than in rings without endothelium; the relaxations were not affected by superoxide dismutase or mannitol, but could be prevented by catalase. Xanthine oxidase plus xanthine depressed endothelium-mediated relaxations to acetylcholine; this effect was prevented by superoxide dismutase, but was not affected by catalase or mannitol. Exogenous hydrogen peroxide induced catalase-sensitive relaxations, which were depressed by the removal of the endothelium. Superoxide dismutase evoked catalase-sensitive relaxations only in rings with endothelium. Endothelium-mediated relaxations to acetylcholine were slightly depressed by superoxide dismutase or catalase alone; the combination of the two enzymes or mannitol caused a major shift to the right of the concentration-response curve to acetylcholine. In rings without endothelium, relaxations caused by sodium nitroprusside were not affected by the scavengers (alone or in combination) but were augmented by xanthine oxidase plus xanthine. These data suggest that the endothelium-derived relaxing factor released by acetylcholine is not likely to be an oxygen-derived free radical; hydrogen peroxide has a direct inhibitory action on coronary arterial smooth muscle and triggers endothelium-dependent relaxations; and superoxide anions depress and hydroxyl radicals facilitate endothelium-dependent relaxations caused by activation of muscarinic receptors.
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PMID:Oxygen-derived free radicals, endothelium, and responsiveness of vascular smooth muscle. 308 20

The primary objective of this study was to determine the effect that the xanthine oxidase inhibitor allopurinol (ALLO) and the hydrogen peroxide scavenger catalase (CAT) have on the cardiovascular compensatory ability of the dog to respond to severe hemorrhagic hypotension. Twenty-four mongrel dogs were anesthetized with sodium pentabarbitol and surgically prepared to monitor 1) average arterial blood pressure (AAP), 2) central venous pressure (CVP), 3) heart rate (HR), 4) cardiac index (CI = CO/kg), and hindlimb skeletal muscle blood flow (MBF). Total body vascular conductance (TBC) and skeletal muscle vascular conductance (MVC) were calculated by dividing the CI or MBF by the difference between the AAP and CVP. Eight animals were placed into each of the following three groups, bled over a 1-hr period of time to an AAP of 50 mm Hg and monitored for an additional 2 hr. Group I controls received an intravenous volume of lactated Ringer's equivalent to that volume given to groups II and III. Group II was pretreated 24 hr prior to hemorrhage with 100 mg/kg ALLO orally and received a bolus injection of 25 mg/kg 15 min prior to hemorrhage plus an intravenous infusion of 5 mg/kg/hr over the 3-hr study. Group III was given the same ALLO treatment as group II plus an additional 5-mg/kg/hr intravenous infusion of CAT throughout the duration of the 3-hr study. The results show that the intense compensatory increase in total body vascular tone which occurs during severe hypovolemia is significantly reduced at the 60-, 120-, and 180-min periods in the ALLO/CAT group; however, when ALLO alone was used this effect lasted only through the 120-min period. A similar, but statistically less convincing, picture was seen in the skeletal muscle vascular bed. Thus, the ALLO/CAT group seemed to inhibit some free radical mechanisms better than the ALLO group during and immediately following hemorrhage. Allopurinol alone lost its effectiveness before the 3 hr, which suggests that a free radical mechanism may play an early role in the pathophysiologic shock sequence. As shock continues, however, other factors seem to override the free radical mechanism. One possible explanation for this early tissue protective action of allopurinol and catalase is the inhibition of the oxygen free-radical-induced microvascular swelling and plugging.
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PMID:The effect of allopurinol and catalase on cardiovascular hemodynamics during hemorrhagic shock. 316 71

A method for measuring the content of two groups of microsomal cytochrome P-450 isozymes--cytochromes P-450W and P-450L--with the active sites directed into the water phase and membrane lipids, respectively, has been developed. The method is based on the ability of the xanthine oxidase-menadione complex to reduce microsomal cytochromes b5 and P-450 under anaerobic conditions by transferring electrons to hemoproteins with the active sites directed into the water phase. Cytochrome b5 is completely reduced (to the dithionite level) and cytochrome P-450 is reduced partially (only a group of cytochromes P-450W). The amount of cytochromes P-450L is estimated using the difference between the total content of cytochrome P-450 reduced by sodium dithionite and the content of cytochromes P-450W. The possibility of controlling the ratio of these two isozyme groups in cytochrome P-450 in vivo in membranes of the endoplasmic reticulum by pretreatment of animals with a variety of chemicals has been demonstrated. The ratio of cytochromes P-450W and P-450L has been shown to decrease two-fold 18 days after three injections of phenobarbital into mice. Carbon tetrachloride and cyclophosphamide also decrease this ratio in vivo.
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PMID:The ratio of two isozyme groups in microsomal cytochrome P-450 under exogenous influence of carbon tetrachloride and cyclophosphamide. 323 47

Milk proteins in acid whey were separated into five fractions according to molecular size by gel filtration chromatography. The second peak, P2, contained proteins between approximately 250,000 and 100,000 daltons. Proteins in P2 were concentrated. After separation into albumins and globulins, each protein group was isolated by DEAE chromatography and hydrophobic interaction chromatography, Isolated albumin fractions were a yellow-colored protein of 89,000 daltons, an unidentified protein of 73,000 daltons, a beta-lactoglobulin of 18,300 daltons, and a red-colored protein of 87,000 daltons. Two types of globulin fractions were isolated: 1) a globulin fraction that coagulated in saturated sodium sulfate but did not coagulate when dialyzed against deionized water included a brown-colored protein of 150,000 daltons, and 2) a bovine serum albumin of 67,000 daltons with unidentified 170,000 and 30,000 daltons bands. A true globulin fraction contained a 77,000 dalton unidentified protein with several faint bands. The red-colored protein was identified as lactoferrin and the brown-colored protein as xanthine oxidase (EC 1.2.3.2.). A yellow-colored protein was concluded to be the denatured protein of contaminated lactoperoxidase (EC 1.11.1.7).
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PMID:Isolation of some minor milk proteins, distributed in acid whey from approximately 100,000 to 250,000 daltons of particle size. 337 95

The morphologic and functional effects of free radicals on renal cells in vitro were investigated, as well as the possibility of avoiding them by pretreatment with scavenger enzymes or a xanthine oxidase inhibitor. Cultured human kidney cells, incubated together with a free radical-generating system, with and without protective agents, were examined by light and scanning electron microscopy. The vimentin filament structure of the incubated cells was visualized by immunofluorescence. The membrane function was studied in human kidney cells by using a dye exclusion test and in rabbit kidney slices by determination of the sodium-potassium pump activity. Exposure of the cells to free radicals caused rapid development of severe morphologic lesions, including extensive cytoskeletal disorganization. After pretreatment, only a few cells had similar, although less severe, lesions. The results of the dye exclusion test and indirect evaluation of the sodium-potassium pump activity did not indicate any major damage to the cell membranes after exposure to free radicals.
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PMID:Protection of renal cells against free radical damage in vitro. A morphologic and functional study on human and rabbit kidney cells. 355 73

Recent studies have implicated oxygen free radicals in ischemia-reperfusion injury to the gastric mucosa. The aims of the present study were to test the hypothesis that the enzyme xanthine oxidase is the source of the oxygen radicals in the ischemic stomach and determine the importance of the iron-catalyzed Haber-Weiss reaction in generating the cytotoxic oxygen radicals. Gastric mucosal clearance of 51Cr-labeled red blood cells was measured during a 30-min control period, a 30-min ischemic period (hemorrhage to 25 mmHg arterial pressure), and a 60-80-min reperfusion period (reinfusion of shed blood). In untreated (control) rats, a dramatic rise (100-fold) in the leakage of 51Cr-labeled red blood cells into the gastric lumen was observed only during the reperfusion period. After the reperfusion period, gastric mucosal damage was further assessed using gross lesion area and histology. Rats were placed on a sodium tungstate diet (to inactivate xanthine oxidase), or treated with either deferoxamine (an iron chelating agent) or superoxide dismutase (a superoxide scavenger). All three interventions substantially reduced 51Cr-labeled red blood cell clearance and gross lesion area relative to untreated rats. However, tissue injury assessed histologically was similar in both treated and untreated animals. The results of this study support the hypothesis that oxygen free radicals mediate the hemorrhagic shock-induced extravasation of red blood cells. The data also indicate that xanthine oxidase is the source of the oxy-radicals and that the iron-catalyzed Haber-Weiss reaction is largely responsible for hydroxyl radical generation in this model.
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PMID:Gastric mucosal injury in the rat. Role of iron and xanthine oxidase. 355 1


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