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

Aqueous solutions of engine exhaust condensation products were derived from cars powered by diesel or four-stroke gasoline engines (with and without three-way catalytic converter). The cars were operated on a static test platform. Samples of the different exhaust solutions accumulated in a Grimmer-type distillation trap (VDI 3872) during standard test programs (Federal Test Procedure) were incubated with important biomolecules. As indicators of reactive oxygen species or oxidative destruction, ascorbic acid, cysteine, glutathione, serum albumin, the enzymes glycerinaldehyde phosphate dehydrogenase and xanthine oxidase, and the oxygen free-radical indicator keto-methylthiobutyrate were used. During and after the incubations, oxygen activation (consumption) and oxidative destruction were determined. Comparison of the oxidative activities of the different types of exhaust condensates clearly showed that the exhaust condensate derived from the four-stroke car equipped with a three-way catalytic converter exhibited by far the lowest oxidative and destructive power.
 ...
PMID:Oxidative destruction of biomolecules by gasoline engine exhaust products and detoxifying effects of the three-way catalytic converter. 128 38

We have previously demonstrated that oxypurinol (40 mg/kg i.p.), a xanthine oxidase inhibitor, can reduce focal ischemic brain injury in the rat when applied pre-ischemically. By using a model of occlusion of the middle cerebral artery (MCA) in tandem with occlusion of the ipsilateral carotid artery, the present study further demonstrates that delayed (60 min) administration of oxypurinol also exhibits a protective action on ischemic damage in the stroked rat brain. Oxypurinol significantly reduced the ischemic cerebral infarct zone by preventing the development of brain damage primarily in areas distant to the central lesion core. A corresponding amelioration of brain swelling and attenuation of neurological deficits were evident. Similar protection against focal ischemic brain damage was evident when the adenosine deaminase inhibitor, deoxycoformycin (500 micrograms/kg), was administered prior to the onset of ischemia. However, with delayed (60 min) administration deoxycoformycin had no protective effect. These findings support the hypothesis that manipulation of adenosine catabolism can be an effective therapeutic approach to the prevention or treatment of brain injuries, such as those occurring during ischemic stroke or cardiac arrest.
 ...
PMID:Deoxycoformycin and oxypurinol: protection against focal ischemic brain injury in the rat. 161 98

A free radical is any species capable of independent existence that contains one or more unpaired electrons. Free radical reactions have been implicated in the pathology of more than 50 human diseases. Radicals and other reactive oxygen species are formed constantly in the human body, both by deliberate synthesis (e.g. by activated phagocytes) and by chemical side-reactions. They are removed by enzymic and nonenzymic antioxidant defence systems. Oxidative stress, occurring when antioxidant defences are inadequate, can damage lipids, proteins, carbohydrates and DNA. A few clinical conditions are caused by oxidative stress, but more often the stress results from the disease. Sometimes it then makes a significant contribution to the disease pathology, and sometimes it does not. Several antioxidants are available for therapeutic use. They include molecules naturally present in the body [superoxide dismutase (SOD), alpha-tocopherol, glutathione and its precursors, ascorbic acid, adenosine, lactoferrin and carotenoids] as well as synthetic antioxidants [such as thiols, ebselen (PZ51), xanthine oxidase inhibitors, inhibitors of phagocyte function, iron ion chelators and probucol]. The therapeutic efficacy of SOD, alpha-tocopherol and ascorbic acid in the treatment of human disease is generally unimpressive to date although dietary deficiencies of the last two molecules should certainly be avoided. Xanthine oxidase inhibitors may be of limited relevance as antioxidants for human use. Exciting preliminary results with probucol (antiatherosclerosis), ebselen (anti-inflammatory), and iron ion chelators (in thalassaemia, leukaemia, malaria, stroke, traumatic brain injury and haemorrhagic shock) need to be confirmed by controlled clinical trials. Clinical testing of N-acetylcysteine in HIV-1-positive subjects may also be merited. A few drugs already in clinical use may have some antioxidant properties, but this ability is not widespread and drug-derived radicals may occasionally cause significant damage.
 ...
PMID:Drug antioxidant effects. A basis for drug selection? 172 62

Understanding of the mechanisms of cell injury and cell death is fundamental to the understanding of both protection against and initiation of cell injury and cell death. We subjected primary cultures of proximal tubular epithelium (PTE) from adult rats to an exogenous oxidative stress, generated by xanthine/xanthine oxidase (X/XOD), and studied its effect on the concentration of cytosolic ionized calcium ([Ca2+]i) by means of digital imaging fluorescence microscopy (DIFM) using a cytosolic calcium probe, fura-2. Exposure to 25 mU/ml X/XOD caused notable increases in [Ca2+]i detectable within 15 sec and increasing to micromolar levels with time. Experiments with Ca(2+)-free medium containing ethylene glycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid (EGTA) showed that the increase of [Ca2+]i was due to influx from the extracellular space. Smaller and slower increases in [Ca2+]i were seen after exposure to lower concentrations of X/XOD (5 and 10 mU/ml). PTE injury and killing were assessed by measuring the release of cytosolic lactate dehydrogenase (LDH), exclusion of trypan blue, and observation of morphologic changes. Exposures to the 25 mU/ml concentration of X/XOD caused significant LDH release after 2 hr and correlated with trypan blue staining of exposed cells. Again, lesser concentrations of X/XOD resulted in a slower release of smaller amounts of LDH, and thus delayed trypan blue staining. Cytoplasmic bleb formation was seen by phase microscopy within minutes of exposure to 25 mU/ml, followed by cell rounding, retraction, and disintegration. Transmission electron microscopy revealed a progression of changes characteristic of lethal cell injury, beginning with dilatation of the endoplasmic reticulum, detachment of ribosomes, condensation of mitochondria, and chromatin clumping and terminating with mitochondrial swelling and formation of intramitochondrial flocculent densities. These studies clearly show that notable increases of [Ca2+]i precede both sub-lethal and lethal changes in rat PTE. These results indicate that interventions designed to minimize or to accelerate calcium entry could be of importance in cell preservation or cell killing, respectively, and therefore to therapeutic strategies for myocardial infarction, stroke, or shock in the former instance and for cancers in the latter.
 ...
PMID:Oxidative injury induces influx-dependent changes in intracellular calcium homeostasis. 177 66

The reperfusion of previously ischemic tissue may lead to the formation of highly reactive free radicals that promote tissue injury. Xanthine oxidase has been implicated as one source of these free radicals. We examined the role of xanthine oxidase in brain injury using a cerebrospinal fluid compression model of global cerebral ischemia with 15 minutes of ischemia and 4 hours of reperfusion. Seven dogs were pretreated with the xanthine oxidase inhibitor allopurinol (50 mg/kg for 5 days). Neurophysiological recovery was monitored with cortical somatosensory evoked potentials. As an attempt to correlate brain recovery with the mechanism of protection, free brain malondialdehyde was measured at the end of reperfusion by high-performance liquid chromatography. Brain water content was measured by wet-dry weights. Compared with seven untreated control dogs, allopurinol pretreatment significantly improved recovery of somatosensory evoked potentials after 4 hours of reperfusion. However, the amount of free malondialdehyde in the allopurinol-treated dogs was 32% greater than that in the controls. Brain water content was similar in the two groups. These results suggest that xanthine oxidase contributes to brain injury after ischemia and reperfusion. However, tissue damage caused by xanthine oxidase may be mediated through mechanisms other than free radical production.
Stroke 1991 May
PMID:Allopurinol pretreatment improves evoked response recovery following global cerebral ischemia in dogs. 202 98

The effects of oxygen-derived free radicals on the contractile activity of the mesenteric collecting lymphatics were evaluated in the anesthetized rat. Lymphatic contractions were monitored before, during and after the application of oxyradicals. Contraction frequency (F), stroke volume (SV), ejection fraction (EF), contraction propagation (PC), and lymph pump flow (LPF) were determined from the lymphatic diameter tracings. Oxyradicals were generated using hypoxanthine and xanthine oxidase. Exposure to oxyradicals inhibited the lymphatic pumping mechanism: 1) F fell from 15.5 +/- 0.8 to 0.8 +/- 0.7 beats/min; 2) EF went from 0.44 +/- 0.02 to 0.08 +/- 0.04; 3) PC dropped from 92 +/- 2 to 56 +/- 8%; and 4) LPF fell precipitously from 41.0 +/- 5.2 to 0.7 +/- 0.4 nl/min. The effects of the oxyradicals were attenuated by superoxide dismutase, implicating superoxide anion as one of the predominant causative agents. We conclude that oxyradicals significantly inhibit the lymph pump and that this inhibition could be a factor contributing to the formation of interstitial edema during inflammation.
 ...
PMID:Reactive oxygen metabolites inhibit spontaneous lymphatic contractions. 205 26

Acute cerebral ischemia increases the generation of free radicals, causing cell damage, and theoretically may decrease the activity of the scavenging enzyme superoxide dismutase. To investigate the role of superoxide dismutase in cerebral ischemia, we used a model of middle cerebral artery occlusion in rats. In this model an infarct is produced in the pyriform and frontoparietal cortices, extending into the lateral basal ganglia. We measured superoxide dismutase activity by using the xanthine oxidase cytochrome c reduction assay in these areas of rat brains. Tissue samples were analyzed 20 minutes, 2, 6, or 24 hours, or 7 days after middle cerebral artery occlusion and 2 or 24 hours or 7 days after sham operation (n = 8-10 at each time). There was no significant change in superoxide dismutase activity relative to control values in any brain area at any time up to 24 hours after surgery. However, 7 days after middle cerebral artery occlusion a significant decline in superoxide dismutase activity, to 55%-68% (p less than 0.05) of that in unoperated controls, was observed in all brain areas. Our results do not support an important role for changes in the activity of endogenous superoxide dismutase during the acute phase of cerebral ischemia. However, the decrease in superoxide dismutase activity 7 days after ischemia could indicate ongoing additional damage to peri-infarct tissue.
Stroke 1990 Nov
PMID:Effect of ischemia induced by middle cerebral artery occlusion on superoxide dismutase activity in rat brain. 223 56

Free radicals have been shown to play an important role in ischemia-reperfusion injury in several organ systems; however, the role of free radicals in central nervous system ischemia has been less well studied. Many potential free radical-generating systems exist. The primary products of these reactions, superoxide and hydrogen peroxide, may combine to produce hydroxyl radicals. Of the many potential sources of free radical generation, the enzyme xanthine oxidase has been shown to be important in ischemia in noncerebral tissue. We investigated the effect of the hydroxyl radical scavenger dimethylthiourea and the xanthine oxidase inhibitor allopurinol on infarct volume in a model of continuous partial ischemia. Male Sprague-Dawley rats were treated with dimethylthiourea or allopurinol before middle cerebral artery occlusion. Infarct volume was measured by triphenyltetrazolium chloride staining of brains removed 3 or 24 hours after occlusion. Stroke volume was reduced by 30% after dimethylthiourea treatment and by 32-35% after allopurinol treatment. At 24 hours after stroke, cortical tissue was more effectively protected than caudate tissue with both agents. Pretreatment with dimethylthiourea and allopurinol also significantly reduced cerebral edema formation and improved blood-brain barrier function as measured by fluorescein uptake. Our results imply that hydroxyl radicals are important in tissue injury secondary to partial cerebral ischemia and that xanthine oxidase may be the primary source of these radicals.
Stroke 1989 Apr
PMID:Allopurinol and dimethylthiourea reduce brain infarction following middle cerebral artery occlusion in rats. 246 8

In spontaneously hypertensive rats, we studied the participation of xanthine oxidase-linked free radical in ischemia and reperfusion-induced cerebral injury, using allopurinol, a xanthine oxidase inhibitor. The loss of righting reflex was noted in some animals after a 4 hour occlusion of bilateral common carotid arteries and 19 of 25 animals died within 72 hours after reperfusion. One hour after reperfusion, the cerebral water content increased significantly, with an increase in sodium content and a decrease in potassium content. In 7 animals treated with oral administrations of allopurinol (200 mg/kg) 24 hours and 1 hour before occlusion, no death was found either during occlusion or after reperfusion, and the loss of righting reflex was noted in only one animal 24-72 hours following reperfusion. The increase in cerebral water content and accompanied changes in electrolyte contents were clearly prevented by allopurinol. These results suggest the possibility that the production of xanthine oxidase-linked free radical participates in cerebral injury due to ischemia and reperfusion in spontaneously hypertensive rats.
Stroke
PMID:Effect of allopurinol on ischemia and reperfusion-induced cerebral injury in spontaneously hypertensive rats. 302 24

Tissue damage as a consequence of ischemia is a major medical problem in an industrialized society. Whereas the conventional view has attributed this injury process to ischemia itself, recent studies have found that a variable, but often substantial proportion of the injury is caused by toxic oxygen metabolites that are generated from xanthine oxidase at the time of reperfusion. This mechanism was first identified and characterized in a model of moderately mild partial vascular occlusion in the feline small intestine. Strikingly similar mechanisms have been subsequently confirmed as the basis for ischemia/reperfusion injury in the stomach, pancreas, liver, skin, skeletal muscle, heart, lung, kidney and central nervous system. The potential for clinical application of this concept is related primarily to that proportion of the total post-ischemic injury that is due to this reperfusion mechanism, set against the proportion due to ischemia itself. Ironically, in clinical cases of intestinal ischemia the reperfusion component appears to be proportionately small, and the potential for treatment of ischemic bowel disease is correspondingly limited. On the other hand, there is reason to expect that the ablation of free radical-mediated reperfusion injury, something that can be readily achieved through non-toxic means, may provide substantial benefit for the treatment of ischemic renal disease, myocardial infarction, stroke, cardiac arrest, and of organs preserved for transplantation.
 ...
PMID:Free radical-mediated reperfusion injury: a selective review. 330 76


1 2 3 4 5 6 Next >>