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 antiperoxidant action of berbamine (Ber) was demonstrated by colorimetric estimation of malondialdehyde (MDA) formation, and the scavenging effect of Ber on O2- was investigated by chemiluminescence method and ESR-spin trapping technique. Ber 11-100 mumol/L remarkably inhibited MDA formation induced by incubating mice liver homogenate at 37 degrees C with vibration for 1 h. Ber 1-100 mumol/L and 0.2-0.6 mmol/L effectively scavenged O2- in alkaline DMSO and xanthine/xanthine oxidase systems respectively. The results show that Ber is an antioxidant.
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PMID:[Antioxidant effect of berbamine]. 196 56

We used mouse soleus in vitro (n = 30) and canine gastrocnemius-plantaris preparations (n = 20) pump-perfused at the animal's blood pressure to establish if free radicals contribute to fatigue in oxidative skeletal muscle. The soleus from each leg contracted for 200 ms (70 Hz) once every minute for 60 min in Hepes buffer gassed with 100% oxygen at 27 degrees C. When contracting in Hepes alone, both muscles fatigued at 0.9 mN/mm2.min over the 60 min. The addition of purines to the bath increased the rate to 1.4 mN/mm2.min and the addition of xanthine oxidase to generate free radicals increased the rate again to 1.9 mN/mm2.min. Thus free radicals appeared to attenuate oxidative skeletal muscle function. Each canine muscle contracted isometrically at 4 Hz for 30 min and then rested for 45 min before contracting for a second 30 min at 4 Hz. In each experiment, we infused saline at 0.76 mL/min into resting muscle and at 1.91 mL/min during the first contraction period. During the remainder of the experiment, we infused, at the same rates, saline (n = 4), 10 microM dimethyl sulfoxide (DMSO) (n = 4) to identify the effect of scavenging hydroxyl radicals, 1 mM allopurinol to establish the effect of blocking xanthine oxidase (n = 4), or 200 microM desferoxamine to determine the effect of chelating iron (n = 4). With saline, the fatigue rate over the 30 min of contractions increased from 5.0 +/- 0.2 to 6.3 +/- 0.5 N/kg.min from the first to the second stimulation period. The fatigue rate was slower in the second period with each of the three experimental substances (DMSO, 5.9 +/- 0.8 to 3.2 +/- 0.3; allopurinol, 7.3 +/- 1.1 to 4.6 +/- 0.6; desferoxamine, 6.8 +/- 0.8 to 4.4 +/- 0.8 N/kg.min). The fatigue rate was the same as control when DMSO was infused only during the second contraction period. Therefore, free radicals appeared to contribute to fatigue in oxidative skeletal muscle.
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PMID:Free radicals may contribute to oxidative skeletal muscle fatigue. 205 45

This study investigated whether or not oxygen-derived free radicals are implicated in the mechanism of recurrence of duodenal ulceration. To this end, allopurinol (50 mg qds)--a hydroxyl scavenger and an inhibitor of xanthine oxidase which forms superoxide radicals--and dimethyl sulphoxide (DMSO, 500 mg qds)--a hydroxyl scavenger--were given orally. Three hundred and two consecutive patients with previous symptomatic, endoscopy-proven duodenal ulceration which had been shown endoscopically to have healed and who were smokers and social drinkers, were randomized to receive for one year either placebo, cimetidine 400 mg at bedtime, allopurinol, or DMSO. In two hundred and twenty patients evaluable for efficacy, the cumulative relapse at one year was: placebo 65%, cimetidine 30%, allopurinol 12% and DMSO 13%. Cimetidine was significantly effective (p less than 0.01); however, allopurinol and DMSO were equally efficacious and superior to cimetidine (p less than 0.05). In patients who relapsed, the ulcer recurrence tended to occur early on placebo and to be evenly distributed over the year on active therapy. In all the groups, the relative frequency of symptomatic to silent relapses was similar in the first and second halves of the year and was comparable among the groups. The results suggest that oxygen-derived free radicals are directly implicated in the mechanism of duodenal ulcer relapse and that removing the radicals reduces recurrence of this ulceration.
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PMID:Oxygen-derived free radicals and the prevention of duodenal ulcer relapse: a new approach. 216 71

We previously documented a relationship between xanthine oxidase activation, intestinal injury, and bacterial translocation (BT) in rats subjected to hemorrhagic shock. The current experiments were performed to determine the relative roles of hydroxyl radicals and neutrophils in the pathogenesis of shock-induced mucosal injury and BT. The incidence of BT was higher in the shocked rats (30 mm Hg for 30 min) than the sham-shock controls (87% vs 12.5%; p less than 0.01). Administration of the hydroxyl radical scavenger, dimethyl sulfoxide (DMSO), or the iron chelator, deferoxamine, reduced the incidence of BT from 87% to 20% and 40%, respectively (p less than 0.05). DMSO and deferoxamine appear to prevent shock-induced BT by blunting the magnitude of shock-induced mucosal injury. In contrast, neutrophil depletion did not prevent BT or protect the intestinal mucosa in shocked rats. Instead, the incidence of systemic spread of translocating bacteria past the mesenteric lymph nodes to the livers and spleens of the shocked rats was higher in the neutrophil-depleted rats (56%) than in any other group (p less than 0.01). Thus, shock-induced BT and intestinal injury appear to be mediated by oxidants (.OH) derived from xanthine oxidase, rather than granulocytes.
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PMID:Hemorrhagic shock-induced bacterial translocation: the role of neutrophils and hydroxyl radicals. 216 88

Bepridil, a calcium antagonist with anti-anginal, anti-ischemic, and anti-arrhythmic properties was assessed for its ability to scavenge free radicals. Bepridil reduced the stable free radical 1,1-diphenyl-2-picrylhydrazil (DPPH) in the molar ratio 2:1 and, in this respect, was as active as the reference anti-oxidants hydroquinone and alpha-tocopherol. Allopurinol and SOD inhibited cytochrome c reduction in a hypoxanthine-xanthine oxidase superoxide generating system, whereas bepridil was ineffective. Deoxyribose degradation induced by the .OH radical was prevented by bepridil (IC50 = 0.050 mM). This ability to scavenge .OH was similar to that of dimethyl sulfoxide (DMSO) (IC50 = 0.056 mM) and more potent than that observed with mannitol and allopurinol (IC50 values of 0.74 mM and 0.92 mM, respectively). The powerful .OH scavenging activity of bepridil was confirmed in vivo on alloxan induced diabetes in mice. Bepridil exerted a marked protective effect at 0.150 mmol/kg whilst, ethanol and DMSO were active at the doses of 90 and 94 mmol/kg, respectively. These results demonstrate that bepridil is a potent .OH radical scavenger. This property may contribute to the therapeutic activity of this drug in myocardial ischaemia.
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PMID:Studies on the activity of bepridil as a scavenger of free radicals. 217 34

Intestinal ischemia, however, caused, is still a serious and growing clinical problem with an unacceptable mortality rate of over 60%. This high mortality rate is mainly due to the fact that the patients are not admitted to the hospital or not treated early enough. Even if the patients are operated on within 24 h, their mortality rate is still over 50%, and those surviving the initial treatment suffer from postischemic complications. These damages have been accounted until now to tissue ischemia. It has been proven experimentally that also reperfusion or revascularization after time-limited ischemia add to the tissue damages observed, due to the formation of O2-radicals. Thereby the prerequisites for the production of these radicals (the conversion of xanthine dehydrogenase to xanthine oxidase and the increase of hypoxanthine concentrations in the tissue and plasma) are generated during tissue ischemia. These radicals damage directly or initiate several vicious circles leading to mucosal lesions, impaired intestinal function and an enhanced absorption of bacteria and endotoxin. Various substances (SOD, catalase, DMSO, allopurinol, deferoxamine etc.) detoxify oxygen radicals or inhibit the pathomechanisms leading to the enhanced radical generation. Hopefully, the combination of early revascularization with these already available scavengers will improve the high mortality and morbidity of patients suffering from intestinal ischemia.
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PMID:Oxygen radicals in intestinal ischemia and reperfusion. 222 27

The reactions of superoxide radical with persistent nitroxide spin-adducts or with stable spin-labels were studied using ESR spectrometry. Superoxide radicals were produced enzymatically using xanthine - xanthine oxidase or chemically by dissolving potassium superoxide in DMSO. Hydroxyl and methyl spin-adducts of the spin-trap DMPO were performed by sonolysis and subsequently reacted with superoxide radical. Superoxide-induced depletion of DMPO--OH obeyed second order kinetics. Contrary to previously published mechanisms, the reaction requires neither transition metal ions nor thiols. The depleted spin-adducts could not be restored by reoxidation with ferricyanide or copper +H2O2; thus, the superoxide-mediated destruction does not result in a mere one-electron reduction product. Superoxide also depletes other DMPO spin-adducts including DMPO--CH3 and DMPO--H, but not PBN--CH3. In addition, some 5-membered ring stable nitroxides are depleted by superoxide in a pseudo-zero order reaction. In studying systems which generate O2- and OH, the superoxide-induced destruction of DMPO--OH may well lead to erroneous conclusions regarding the primary radicals produced. In particular this reaction might be operative under circumstances where elevated rates of superoxide production take place, such as during oxygen consumption "burst" in phagocytosis, degranulation, or paraquat intoxication.
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PMID:Superoxide reaction with nitroxide spin-adducts. 254 65

These studies were designed to assess pathophysiologic factors responsible for increased vascular permeability occurring in rat skin that has been thermally injured in vivo. Under the conditions employed, permeability changes and edema formation progressed over time, with peak changes occurring 60 minutes after thermal trauma. The plasma of thermally injured rats showed dramatic increases in levels of xanthine oxidase activity, with peak values appearing as early as 15 minutes after thermal trauma. Excision of the burned skin immediately after thermal injury significantly diminished the increase in plasma xanthine oxidase activity. The skin permeability changes were attenuated by treatment of animals with antioxidants (catalase, superoxide dismutase [SOD], dimethyl sulfoxide [DMSO], dimethylthiourea [DMTU]) or an iron chelator (deferoxamine), supporting the role of oxygen radicals in the development of vascular injury as defined by greatly increased vascular permeability. Studies employing laser Doppler velocimetry in thermally injured skin revealed a pronounced and sustained decrease in blood flow after thermal trauma, a pattern not affected by protective interventions. The failure of neutrophil depletion to protect against the vascular permeability changes and the protective effects of the xanthine oxidase inhibitors (allopurinol and lodoxamide tromethamine) suggest that xanthine oxidase is the most likely source of the oxygen radicals involved in edema formation. Lodoxamide was found to have some hydroxyl radical (HO.) scavenging ability (greater than that of allopurinol) but no iron chelating activity. Some of the protective effects of lodoxamide and allopurinol may be linked to their HO. scavenging ability. These data suggest that, in this model of thermal trauma, vascular injury defined by increased vascular permeability is, in part, related to the activation of xanthine oxidase and the generation of toxic oxygen metabolites that damage microvascular endothelial cells.
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PMID:Role of xanthine oxidase in thermal injury of skin. 254 94

It has been reported that oxygen-derived free radicals play an important role in the pathogenesis of mucosal injury in the small intestine as well as in the stomach. The aims of this study were to test whether ethanol-induced damage in the rat stomach was prevented by the administration of (1) superoxide dismutase (SOD; a scavenger of superoxide radicals), (2) allopurionol (ALP; an inhibitor of xanthine oxidase), (3) dimethyl sulfoxide (DMSO; a scavenger of hydroxyl radicals). SOD significantly decreased the ulcer index from 100 +/- 8.5% (control) to 39.6 +/- 8.2% (P less than 0.001). Ethanol-induced damage was reduced by the administration of ALP by 37.4% (P less than 0.01). DMSO also diminished the ulcer index from 100 +/- 8.5% (control) to 31.6 +/- 5.8% (P less than 0.01). Histochemical studies supported these results. A scanning EM study, however, revealed that surface epithelial cells were not protected by SOD against ethanol-induced damage. These results demonstrated that SOD, ALP and DMSO had the ability to protect gastric mucosa against ethanol-induced injury. Accordingly, oxygen-derived free radicals may be involved in the pathogenesis of ethanol-induced gastric mucosal damage. Surface epithelial cells, however, were not protected even by SOD against ethanol-induced injury.
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PMID:Role of superoxide and hydroxyl radicals in rat gastric mucosal injury induced by ethanol. 255 24

In the present work, an experimental system was designed to study superoxide anion radical, implicated as the cause of vascular dilatation. To circumvent its direct effect, we employed a two-bath system. When the endothelial cells (EC) were exposed to electrical field stimulation (EFS) or to a hypoxanthine-xanthine oxidase system in bath A plus its physiological buffer solution suffused on a helical strip of cat basilar artery in bath B, the contraction to 5-hydroxytryptamine (5-HT) was depressed to approximately 40-50% of the control value. The reduction was not elicited on EFS in a state of calcium deficiency or in the absence of EC. The depression could be prevented by pretreatment with superoxide dismutase (SOD), but not with an effective dose of catalase, dimethyl sulfoxide (DMSO), mannitol, or indomethacin. The percent depression of contraction was paralleled by an increase in SOD-inhibitable cytochrome c reduction, which was not associated with cyclic guanosine 3',5'-monophosphate formation. These results suggest that superoxide-dependent relaxing factor is released from EC differently than the endothelium-derived relaxing factor mediated by acetylcholine.
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PMID:Release of superoxide-dependent relaxing factor(s) from endothelial cells. 255 45


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