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)

Reactive oxygen species such as OH, peroxynitrite and the non-radical, hypochlorous acid, play outstanding roles in many disease. The formation of OH (Fenton)-type radicals is catalyzed by enzymes such as xanthine oxidase (XOD) via one-electron reduction of molecular oxygen producing superoxide radical anions (O2). Subsequent transfer of one electron to hydrogen peroxide by Fe2+ or Cu+ -ions yields OH-radicals measurable as ethene release from 1-keto-4-methylthiobutyrate (KMB). Xanthine oxidase or activated neutrophils are prominent sources of this strong oxidant produced at inflammatory sites. Many natural compounds such as salicylates or flavonoids interfere either with the production of these activated oxygen species or function as radical scavengers and thus as antioxidants. Extracts from willow-bark (Salix spec.) and also other species such as ash-tree (Fraxinus spec.) or poplar (Populus spec.) have been used as antiinflammatory drugs since a long time. In this communication we wish to report on model reactions to demonstrate a) the radical scavenging activities of such plant extracts inhibiting ethene release from KMB induced by Fenton-type oxidants and b) the inhibition of the formation of nitrogen monoxide (NO) from hydroxylamine including XOD either in the presence or absence of myoglobin (MYO) measurable as nitrite formation: In the absence of MYO, superoxide dismutase is an excellent inhibitor of nitrite formation but is inactive in its presence. Extracts from the willow-bark or the drug Phytodolar however, are inhibitory both in the presence and absence of MYO. As active principle, the flavonoid rutin included in these extracts is likely to function as one inhibitor of the XOD-mediated reaction.
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PMID:Superoxide-dependent and -independent nitrite formation from hydroxylamine: inhibition by plant extracts. 968 63

Chemoprevention of free radical-mediated diseases including cancer by natural products is an emerging discipline due to its wider applicability and acceptance. The present study deals with the chemopreventive effect of Salix caprea against phorbol ester-induced oxidative stress and tumor promotion in murine skin. In the present investigation, it was observed that a single application of 12-O-tetradecanoyl-13-phorbol acetate (TPA) (20 nmol/0.2 ml acetone/animal) caused a significant (P < 0.05) depletion of cutaneous antioxidants viz., glutathione, glutathione reductase, glutathione peroxidase, catalase and phase II drug metabolizing enzymes viz., glutathione-S-transferase, quinone reductase. An increase in the hydrogen peroxide generation and protein oxidation (measured in terms of protein carbonyl content) was also observed with a single application of TPA. However, the pretreatment of animals with different doses of Salix caprea (0.5, 1.0 and 1.5 mg/kg/0.2 ml acetone) caused a significant recovery in the TPA-mediated depletion in antioxidant levels. The pretreatment of animals with Salix caprea was observed to inhibit the TPA-mediated depletion in phase II enzymes. It was also observed that Salix caprea reversed the TPA-mediated depletion in the activity of phase II enzymes that is an important characteristic of cancer chemopreventive agents. Phorbol esters are known to induce the tumor promotion by increasing rate of DNA synthesis, ornithine decarboxylase activity (ODC), and xanthine oxidase activity. In the present investigation, it was observed that the pretreatment of animals with Salix caprea caused a significant (P < 0.05) depletion in the TPA-induced DNA synthesis, ODC and xanthine oxidase activity in mice skin. Salix caprea significantly reduced the tumor promotion in mice skin when tested in two-stage chemical carcinogenesis model. It was observed to inhibit significantly P < 0.05) the 7,12-dimethyl benz[a] anthracene (DMBA)-initiated phorbol ester promoted skin carcinogenesis. It was concluded from the results that Salix caprea is an effective antioxidant and chemopreventive agent against phorbol ester-induced tumor promotion.
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PMID:Salix caprea inhibits skin carcinogenesis in murine skin: inhibition of oxidative stress, ornithine decarboxylase activity and DNA synthesis. 1512 Apr 50

Superoxide (O2-) enhances Na reabsorption by the thick ascending limb (THAL). Na absorption in this segment involves the Na-K-2Cl cotransporter, K channel, and Na-K-ATPase. We hypothesized that O2- stimulates NaCl absorption primarily by enhancing Na-K-2Cl cotransport. First, we measured steady-state intracellular Na (Nai) and chloride (Cli). Xanthine oxidase (XO; 0.75 mU/ml) and hypoxanthine (HX; 0.125 mM) were added to the bath to increase O2-. During the control period, Nai was 12.2 +/- 1.9 mM. After treatment with O2-, it rose to 20.9 +/- 3.3 mM, a 71% increase (P < 0.01). Cli also increased (P < 0.01). Neither XO nor HX alone had a significant effect on Nai or Cli. Next, we tested cotransport activity by measuring the initial rate of increase in Nai caused by changing luminal Na-Cl-K from 50/0/0 to 140/134/4 mM. During the control period, the initial rate of increase was 0.13 +/- 0.02 arbitrary units (AU)/min. After treatment with O2-, it was 0.22 +/- 0.04 AU/min (P < 0.025), a 69% increase. Neither XO nor HX alone had a significant effect. Furosemide completely blocked the increase in intracellular Na in the control and O2- treatment periods. Next, we studied K channel activity by measuring the depolarization caused by increasing luminal K from 1 to 25 mM using a voltage-sensitive dye. During the control period, maximum depolarization was 7.31 +/- 0.77 AU. After O2- treatment, it was 6.18 +/- 0.90 AU (P < 0.05), a 15% decrease. Finally, we assessed the effects of O2- on Na-K-ATPase activity in THAL suspensions by measuring ATP hydrolysis. Vmax and K1/2 for Na were not affected by O2-. We concluded that O2- stimulates THAL NaCl absorption primarily by enhancing Na entry via Na-K-2Cl cotransport.
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PMID:Superoxide enhances Na-K-2Cl cotransporter activity in the thick ascending limb. 1582 Dec 59