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)

In an earlier communication we reported that Nigella sativa suppresses potassium bromate-induced renal oxidative damage. In the present study, we report the chemopreventive effect of Nigella sativa against ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative stress, hyperproliferative response and renal carcinogenesis. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances renal lipid peroxidation, xanthine oxidase, gamma-glutamyl transpeptidase and hydrogen peroxide (H2O2) generation with reduction in renal glutathione content, antioxidant enzymes and phase II metabolizing enzymes. It also caused increase in blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and thymidine [H] incorporation into renal DNA. It also enhanced DEN (N-diethylnitrosamine)-initiated renal carcinogenesis by increasing the percentage incidence of tumours. Treatment of rats orally with Nigella sativa (50 and 100 mg/kg body weight) resulted in significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity, DNA synthesis (P<0.001) and incidence of tumours. Renal glutathione content (P<0.01), glutathione-metabolizing enzymes (P<0.001) and antioxidant enzymes were also recovered to significant levels (P<0.001). Thus, our data suggest that Nigella sativa is a potent chemopreventive agent and suppresses Fe-NTA-induced oxidative stress, hyperproliferative response and renal carcinogenesis in Wistar rats.
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PMID:Inhibition of two stage renal carcinogenesis, oxidative damage and hyperproliferative response by Nigella sativa. 1578 20

We conducted a Medline search for controlled studies evaluating currently available drugs for pharmacological neuroprotection. They had to be administered prior to transient global cerebral ischaemia without further non-pharmacological measures. We deliberately excluded focal ischaemia since its pathophysiology is substantially different from global ischaemia. A total of 45 articles conducted exclusively in laboratory animals met these criteria. The following classes of agents were evaluated: anaesthetics, GABAergic drugs, calcium-antagonists, anticonvulsives, sodium-channel blockers, potassium-channel activators, NMDA-receptor antagonists, hormones, vasodilators, dopamine- and alpha2-agonists, magnesium, xanthine oxidase- and cyclooxygenase inhibitors, a nootropic, a protease inhibitor, and immunosuppressants. Some of them were applied chronically and others administered via clinically impracticable routes. The available literature favours isoflurane, phenytoin, lamotrigine, magnesium, and potentially, nimodipine, and flunarizine. If factors like costs, toxicity, side effects, route and mode of application are considered, isoflurane and MgSO4 that have also been safely applied to patients with compromised left ventricular pump function are advantageous but their true role in human neuroprotection remains unclear.
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PMID:A systematic review of currently available pharmacological neuroprotective agents as a sole intervention before anticipated or induced cardiac arrest. 1579 72

The purpose of the present study was to investigate whether the local prevention of luminal superoxide-mediated biological damage in the rat jejunal mucosa could be achieved by liposomal superoxide dismutase (SOD) and the SOD mimic tempamine (TMN). Cationic liposomes loaded with either SOD or TMN were perfused in the rat jejunum prior to the induction of oxidative insult. Reactive hydroxyl radicals were generated in situ in a closed circulating intestinal loop of the rat from the reaction between hypoxanthine and xanthine oxidase in the presence of chelated ferrous sulfate. Mucosal activity of lactate dehydrogenase and levels of potassium ions were used to quantify the tissue damage. Intracellular uptake and locality of SOD were examined in HT-29 cells. The intestinal uptake of SOD and TMN was further measured by using rat colon sacs. Entrapment in cationic liposomes was found to significantly enhance the antioxidant effect of SOD and TMN against the induced oxidative damage in the jejunal mucosa, compared with their free forms. The effect was found to be local and was caused by the increased mucosal adhesion of the liposomes. The cationic liposomes also triggered SOD uptake into the HT-29 cell line. It is concluded that the increased residence time of the cationic liposomes of SOD and TMN in the jejunal mucosa resulted in a local effect against oxidative injury. This local protection may be exploited for drug delivery purposes.
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PMID:Local prevention of oxidative stress in the intestinal epithelium of the rat by adhesive liposomes of superoxide dismutase and tempamine. 1580 72

We investigated the hypouricemic effects of cassia oil extracted from Cinnamomum cassia using hyperuricemic mice induced by potassium oxonate, and its inhibitory actions against liver xanthine dehydrogenase (XDH) and xanthine oxidase (XOD) activities. Oral administration of cassia oil significantly reduced serum and hepatic urate levels in hyperuricemic mice in a time- and dose-dependent manner. At doses of 450 mg/kg of cassia oil or above, serum urate levels of the oxonate-pretreated mice were not different from the normal control mice. Cassia oil at 600 mg/kg was found to be as potent as allopurinol, which reduced hepatic urate levels to lower than normal. In normal mice, urate levels in liver, but not in serum, were altered with dose-dependent decrease after cassia oil treatment. Furthermore, the ratio, liver uric acid/serum uric acid, was determined after cassia oil administration with time- and dose-dependent decreases in hyperuricemic mice. The positive dose-dependent decrease ratio was also observed after cassia oil treatment in the normal animals. The decreased extent of ratio elicited by cassia oil in normal mice appeared to be greater than that in the hyperuricemic animal. In addition, cassia oil significantly exhibited marked reductions in liver XDH/XOD activities, with an apparent dose-dependence in the normal and hyperuricemic mice. The onset of inhibition in enzyme activities elicited by allopurinol was much higher than that elicited by cassia oil. These results suggested that hypouricemic effects of cassia oil could be explained, at least partly, by inhibiting liver in vivo activities of XDH/XOD.
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PMID:Effects of cassia oil on serum and hepatic uric acid levels in oxonate-induced mice and xanthine dehydrogenase and xanthine oxidase activities in mouse liver. 1618 82

Reactive oxygen species (ROS) have the propensity to cause macromolecular damage with consequent modification of cellular function. We investigated the effects of two particular oxidants, superoxide (O2(-)) anions and hydrogen peroxide (H2O2), on oxytocin-induced myometrial contractility using biopsies from women undergoing Caesarean section at term gestation. Isometric tension recordings were performed and concentration-response curves derived after addition of test agents. A maximal reduction in myometrial contractility to 27.2 +/- 4.5% of control was observed followed application of H2O2. The enzyme scavenger catalase (CAT) reduced the inhibitory effect of H2O2 but had little effect at 10-fold lower concentrations. Addition of dialysed xanthine oxidase +/- hypoxanthine significantly inhibited contractility to 23.8.0 +/- 4.2% compared with control. Pre-incubation with superoxide dismutase and CAT diminished this effect. The non-specific potassium channel blocker, tetraethylammonium chloride (1 mM), had no effect on myometrial contractility. We conclude that human myometrium is susceptible to the effects of ROS, which may be produced by reperfusion-ischaemic episodes during labour. Our findings could, in part, explain the weak or prolonged depression of contractions characteristic of myometrial dysfunction culminating in difficult labours.
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PMID:Hydrogen peroxide and superoxide anion modulate pregnant human myometrial contractility. 1618 71

The effects of acacetin (1) and 4,5-O-dicaffeoylquinic acid methyl ester (2), compounds contained in the flowers of Chrysanthemum sinense SABINE, on the serum uric acid level were investigated using the rats pretreated with the uricase inhibitor potassium oxonate as an animal model for hyperuricemia. When administered per orally at doses of 20 and 50 mg/kg, 1 reduced the serum uric acid level by 49.9 and 63.9%, respectively and 2 reduced the level by 31.2 and 44.4%, respectively. On the other hand, when the same doses were given intraperitoneally, both of compounds also exhibited a dose-dependent and more marked reduction of the serum uric acid level (% reduction at 20 and 50 mg/kg were 63.0 and 95.1% in 1, respectively and 66.9 and 86.5% in 2, respectively). Furthermore, the compounds 1 and 2 inhibited the rat liver xanthine oxidase activity with IC(50) values of 2.22 muM and 5.27 muM, respectively. These results demonstrated the hypouricemic action of 1 and 2, which may be attributable to their xanthine oxidase inhibitory activity.
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PMID:Hypouricemic effects of acacetin and 4,5-o-dicaffeoylquinic acid methyl ester on serum uric acid levels in potassium oxonate-pretreated rats. 1632 55

In this study, we investigated the effects and mechanisms of Total Saponin of Dioscorea (TSD) on animal experimental hyperuricemia. Mouse and rat hyperuricemic models were made by orally administering yeast extract paste once a day (30 and 20 g/kg, respectively), for 7 days. Yeast would disturb normal purine metabolism by increasing xanthine oxidase (XOD) activity and generating large quantities of uric acid. This model is similar to human hyperuricemia, which is induced by high-protein diets, due to a purine and nucleic acid metabolic disturbance. Another mouse hyperuricemia model was generated by intraperitoneal injection once with uric acid 250 mg/kg or potassium oxonate 300 mg/kg. Potassium oxonate, a urate oxidase inhibitor, can raise the serum uric acid level by inhibiting the decomposition of uric acid. Likewise, injecting uric acid can also increase serum uric acid concentration. The concentration of uric acid in serum or urine was detected by the phosphotungstic acid method, and the activity of XOD was assayed by a test kit. The results showed that TSD (240, 120 and 60 mg/kg, ig) could significantly lower the level of serum uric acid in hyperuricemic mice. TSD (120 and 60 mg/kg, ig) could also lower the level of serum uric acid in hyperuricemic rats, reduce the activity of XOD in the serum and liver of hyperuricemic rats, and increase the level of urine uric acid concentration as well as 24-hour total uric acid excretion. In conclusion, TSD possesses a potent anti-hyperuricemic effect on hyperuricemic animals, and the mechanism may be relevant in accelerating the excretion and decreasing the production of uric acid.
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PMID:Effect and mechanism of total saponin of Dioscorea on animal experimental hyperuricemia. 1643 41

A novel biosensor for superoxide radical (O(2)(*-)) detection based on Pseudomonas aeruginosa azurin immobilized on gold electrode was designed. The rate constant of azurin reduction by O(2)(*-) was found to be 10(5)M(-1)s(-1) in solution and five times lower, i.e., 0.2 x 10(5)M(-1)s(-1), for azurin coupled to gold by 3,3'-dithiobis(sulfosuccinimidylpropionate) (DTSSP). The electron transfer rate between the protein and the electrode ranged from 2 to 6s(-1). The sensitivity of this biosensor to O(2)(*-) was 6.8 x 10(2)Am(-2)M(-1). The response to the interference substances, such as uric acid, H(2)O(2), and dimethylsulfoxide was negligible below 10 microM. The electrode was applied in three O(2)(*-) generating systems: (i) xanthine oxidase (XOD), (ii) potassium superoxide (KO(2)), and (iii) stimulated neutrophil granulocytes. The latter was compared with luminol-amplified chemiluminescence. The biosensor responded to O(2)(*-) in all three environments, and the signals were antagonized by superoxide dismutase.
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PMID:Electrochemical characterization and application of azurin-modified gold electrodes for detection of superoxide. 1644 92

Anthocyanins, which are responsible for a variety of bright colors (including red, blue, and purple) in fruits, vegetables, and flowers, are consumed as dietary polyphenols. Anthocyanin-containing fruits are thought to decrease coronary heart disease and are used in anti-diabetic preparations. Diabetes is associated with a variety of cardiovascular complications that may be mediated by endothelial dysfunction, and so this study was designed mainly to characterize the influence of a synthesized anthocyanidin derivative (HK-008) over acetylcholine (ACh)-induced relaxation in mesenteric arterial beds isolated from rats. In a glucose-tolerance test in intact rats, HK-008 (30 mg/kg) reduced the glucose level as effectively as the same dose of glibenclamide. The aortic relaxation induced by pinacidil (an ATP-sensitive potassium channel opener) was greatly inhibited by glibenclamide (10 microM), and also significantly inhibited by HK-008 (10 microM). Interestingly, the ACh-induced relaxation in the perfused, preconstricted mesenteric arterial bed was significantly enhanced by HK-008 (10 microM), and this enhancement was significantly attenuated by indomethacin (10 microM). The ACh-induced mesenteric relaxation was impaired by an increase in oxidative stress, viz. superoxide-generating treatment [xanthine oxidase (XO; 0.1 U/ml) plus hypoxanthine (HX; 10 microM)]. However, this impairment was strongly suppressed by HK-008 (10 microM). These results suggest that HK-008 increases endothelium-induced relaxation by suppressing oxidative stress or modulating prostanoids signaling. This compound may therefore be useful against certain cardiovascular disorders.
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PMID:Effects of anthocyanidin derivative (HK-008) on relaxation in rat perfused mesenterial bed. 1700 Nov 14

Xanthine oxidase inhibitory activity was assayed from six species belonging to different families traditionally used for the treatment of gout and related symptoms by indigenous people of India. The aqueous, methanol-water mixture and methanolic extract of these plants were used for the experiment. Of the 18 extracts assayed, 14 extracts demonstrated xanthine oxidase inhibitory activity at 100 microg/ml, among which 10 extracts showed an inhibition greater than 50% and IC(50) values below 100 microg/ml. The methanolic extracts of Coccinia grandis, Datura metel, Strychnos nux-vomica and Vitex negundo showed more than 50% inhibition, hence, they were screened for their in vivo hypouricaemic activity against potassium oxonate-induced hyperuricaemia in mice. Methanolic extracts of Coccinia grandis and Vitex negundo showed a significant decrease in the serum urate level (3.90+/-0.07 mg/dl, P<0.001) and (6.26+/-0.06 mg/dl, P<0.01), respectively, when compared to hyperuricaemic control (11.42+/-0.14 mg/dl). This effect is almost similar to the serum urate level of allopurinol (3.89+/-0.07 mg/dl).
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PMID:Xanthine oxidase inhibitory activity of some Indian medical plants. 1701 77


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