Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sensitivity of fibroblasts derived from patients with chronic actinic dermatitis (CAD) ultraviolet B (UVB), UVA and superoxide radical was examined. Fibroblasts from the skin of 3 patients with CAD showed abnormal hypersensitivity after exposure to mid-UV (UVB) and near-UV (UVA) radiation in both the dividing and quiescent phases. In their dividing phases, the 3 cell strains (CAD1TO, CAD2TO and CAD3TO) exhibited 78, 55 and 82 J/m2 for the mean lethal dose (Do) values in UVB survival curves. In the quiescent phases their Do values were 262, 226 and 165 J/m2, respectively. Regarding UVA sensitivity, Do value in the dividing phases were 4.9, 3.9 and 3.8 x 10(4) J/m2, and in the quiescent phases, 2.0, 1.9 and 1.7 x 10(5) J/m2. Do values were lower than in the cell strains derived from healthy individuals (Do = 120 +/- 18 and 390 +/- 72 J/m2) for UVB sensitivity in the dividing and quiescent phases and (5.9 +/- 0.6) x 10(4) and (3.2 +/- 1.0) x 10(5) J/m2 for UVA sensitivity in the dividing and quiescent phases. DNA repair synthesis was similar between the cell lines. Furthermore, the 3 CAD cell lines showed a higher sensitivity to superoxide radical generated by hypoxanthine/xanthine oxidase treatment. These results suggest that patients with CAD may suffer from a defect in dealing with damage induced by oxygen radicals.
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PMID:Hypersensitivity of skin fibroblasts from patients with chronic actinic dermatitis to ultraviolet B (UVB), UVA and superoxide radical. 166 59

Skin tumor promotion induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) was inhibited by a concurrent and topical application of phthalic acid mono-n-butyl ester cupric salt (PAMBCu) in CD-1 mice initiated with 7,12-dimethylbenz[a]anthracene. PAMBCu inhibited TPA-caused epidermal ornithine decarboxylase (ODC) induction and ear edema formation, i.e. skin inflammation. However, neither PAMBCu nor superoxide dismutase (SOD) inhibited TPA-caused ODC induction in primary cultured mouse epidermal cells. 7-Bromomethylbenz[a]anthracene (BrMBA) is known to be a non-TPA type of tumor promoting agent. Epidermal ODC induction and inflammation caused by BrMBA were not inhibited by a concurrent application of PAMBCu. When mice were topically treated twice with PAMBCu, i.e. concurrently with and 7 h after BrMBA treatment, BrMBA-caused ODC induction was markedly suppressed. The same dose regimen of PAMBCu, however, failed to inhibit tumor promotion and inflammation caused by BrMBA. PAMBCu showed SOD-mimetic activity in superoxide generating systems, i.e. xanthine-xanthine oxidase reaction and TPA-stimulated polymorphonuclear leukocytes (PMN). Mono-n-butyl phthalate, which lacks SOD-mimetic activity, failed to inhibit TPA-caused ODC induction and skin inflammation. Therefore, inhibition by PAMBCu of TPA-caused tumor promotion, epidermal ODC induction and inflammation may be attributable to its SOD-mimetic activity. The results also support the contention that a superoxide anion of non-epidermal cell origin, such as PMN and macrophages, plays a role (probably some enhancing role) in in vivo ODC induction and tumor promotion caused by TPA. Failure of PAMBCu to inhibit BrMBA-caused tumor promotion suggests that superoxide anion generation is not involved in the tumor promoting action of this agent and that the anti-tumor promoting action of PAMBCu is dependent on the nature of the tumor promoting agents.
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PMID:Anti-tumor promoting action of phthalic acid mono-n-butyl ester cupric salt, a biomimetic superoxide dismutase. 211 May 12

It is well known that retinoids are effective in the treatment of various dermatological disorders. It has been reported that retinoids have inhibitory effects on the generation of superoxide (O2-) by stimulated polymorphonuclear leukocytes (PMNs). In the present study, we investigated the effects of retinoids on the generation of O2- and other reactive oxygen species (ROS), including OH., H2O2 and chemiluminescence, by zymosan-stimulated PMNs and in the xanthine-xanthine oxidase system, because these potent ROS may play an important role in PMN-mediated skin inflammation. It was found that some retinoids had antioxidant effects in the PMN system; however, apart from the effect of tretinoin and Ro 10-1670 on OH. generation, none of the retinoids studied inhibited ROS generation in the xanthine-xanthine oxidase system. On the basis of these results, we discuss a possible mechanism connected with the role of ROS by which retinoids have favourable effects on several inflammatory skin disorders.
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PMID:Anti-oxidant effects of retinoids on inflammatory skin diseases. 301 48

Minor hypersensitivity reactions to allopurinol presenting as skin rash occur in approximately 2% of patients. A more severe, albeit rare, hypersensitivity reaction with fever, eosinophilia, dermatitis, renal failure, vasculitis and hepatic dysfunction carries a mortality of up to 20%. The incidence of this severe reaction can probably be reduced by adjusting the dose of allopurinol in patients with impaired renal function. Azathioprine and mercaptopurine are metabolised by xanthine oxidase, the enzyme that is inhibited by allopurinol. Concomitant administration can result in life-threatening neutropenia unless the dose of allopurinol is reduced by approximately 75%. The uricosuric agent benzbromarone has recently been withdrawn from the market because of several cases of fulminant hepatic failure with subsequent death of the patient or liver transplantation.
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PMID:[Life-threatening adverse effects of pharmacologic antihyperuricemic therapy]. 1549 19

Physalis peruviana (PP) is a widely used medicinal herb for treating cancer, malaria, asthma, hepatitis, dermatitis and rheumatism. In this study, the hot water extract (HWEPP) and extracts prepared from different concentrations of ethanol (20, 40, 60, 80 and 95% EtOH) from the whole plant were evaluated for antioxidant activities. Results displayed that at 100 mug/ml, the extract prepared from 95% EtOH exhibited the most potent inhibition rate (82.3%) on FeCl2-ascorbic acid induced lipid peroxidation in rat liver homogenate. At concentrations 10-100 microg/ml, this extract also demonstrated the strongest superoxide anion scavenging and inhibitory effect on xanthine oxidase activities. In general, the ethanol extracts revealed a stronger antioxidant activity than alpha-tocopherol and HWEPP. Compared to alpha-tocopherol, the IC50 value of 95% EtOH PP extract was lower in thiobarbituric acid test (IC50=23.74 microg/ml vs. 26.71 microg/ml), in cytochrome c test (IC50=10.40 microg/ml vs. 13.39 microg/ml) and in xanthine oxidase inhibition test (IC50=8.97 microg/ml vs. 20.68 microg/ml). The present study concludes that ethanol extracts of PP possess good antioxidant activities, and the highest antioxidant properties were obtained from the 95% EtOH PP.
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PMID:Antioxidant activities of Physalis peruviana. 1593 Jul 27

The present study was undertaken to investigate the antioxidative and anti-inflammatory activities of the extract of the flower of Campsis grandiflora (Thunb.) K. Schum. Exposure of human dermal fibroblasts to 50% EtOH extract of Campsis grandiflora flower (ECG) at 10 and 100 microg/ml showed significant protective effect against hydrogen peroxide (300 microM). ECG not only protected cell survival from H(2)O(2)-induced toxicity, but also inhibited the H(2)O(2)-induced leakage of lactate dehydrogenase (LDH) enzyme release and DNA fragmentation significantly. It was also found that ECG showed scavenging activities of radicals and reactive oxygen species with IC(50) values of 20 microg/ml against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and 52 microg/ml against superoxide radicals in the xanthine/xanthine oxidase system, respectively. Topically applied ECG dose-dependently inhibited arachidonic acid (AA)- and 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema in mice. Consistent with its antioxidative properties in vitro, the present results suggest the therapeutic potential of ECG for acute skin inflammation that may involve oxidative tissue damage.
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PMID:Antioxidative and acute anti-inflammatory effects of Campsis grandiflora flower. 1616 96

Free radical formation has been investigated in diverse experimental models of LPS-induced inflammation. Here, using electron spin resonance (ESR) and the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone, we have detected an ESR spectrum of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone radical adducts in the lipid extract of mouse skin treated with LPS for 6 h. The ESR spectrum was consistent with the trapping of lipid-derived radical adducts. In addition, a secondary radical-trapping technique using dimethyl sulfoxide (DMSO) demonstrated methyl radical formation, revealing the production of hydroxyl radical. Radical adduct formation was suppressed by aminoguanidine, N-(3-aminomethyl)benzylacetamidine (1400W), or allopurinol, suggesting a role for both inducible nitric oxide synthase (iNOS) and xanthine oxidase (XO) in free radical formation. The radical formation was also suppressed in iNOS knockout (iNOS(-/-)) mice, demonstrating the involvement of iNOS. NADPH oxidase was not required in the formation of these radical adducts because the ESR signal intensity was increased by LPS treatment in NADPH oxidase knockout (gp91(phox-/-)) mice as much as it was in the wild-type mouse. Nitric oxide (*NO) end products were increased in LPS-treated skin. As expected, the *NO end products were not suppressed by allopurinol but were by aminoguanidine. Interestingly, nitrotyrosine formation in LPS-treated skin was also suppressed by aminoguanidine and allopurinol independently. Pretreatment with the ferric iron chelator Desferal had no effect on free radical formation. Our results imply that both iNOS and XO, but neither NADPH oxidase nor ferric iron, work synergistically to form lipid radical and nitrotyrosine early in the skin inflammation caused by LPS.
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PMID:Free radical production requires both inducible nitric oxide synthase and xanthine oxidase in LPS-treated skin. 1653 16