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)

Bleomycin, in the presence of ferric salts, oxygen and a suitable reductant, degrades DNA with the release of base propenals, detected as thiobarbituric acid (TBA) reactivity, and the formation of 8-hydroxydeoxyguanosine (8OHdG) detected by HPLC. When xanthine oxidase is added to the incubated mixture of DNA degradation products, TBA-reactivity is destroyed but 8OHdG formation is increased. EPR Spin trapping experiments show that hydroxyl radicals (OH) are formed in the reaction mixture and can be inhibited by the inclusion of either superoxide dismutase or catalase. These findings suggest that the base propenals and possibly malondialdehyde, formed from them, are aldehydic substrates for xanthine oxidase and, the product of this reaction is superoxide (O2-) and hydrogen peroxide (H2O2). Thus, TBA reactivity is destroyed in the formation of O2- and H2O2 which stimulate further oxidative damage to DNA resulting in increased 8OHdG formation.
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PMID:Bleomycin-iron damage to DNA with formation of 8-hydroxydeoxyguanosine and base propenals. Indications that xanthine oxidase generates superoxide from DNA degradation products. 169 21

We have investigated the effect of the soybean isoflavone genistein on 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in calf thymus DNA exposed to either UV irradiation or the Fenton reaction system. Under the conditions used we observed that UV light and the Fenton reaction significantly increase 8-OHdG formation in DNA. Co-incubation with genistein inhibits the formation of 8-OHdG induced by either UV light irradiation or the Fenton reaction in a dose-dependent manner. The quenching effect of genistein on 8-OHdG formation induced by UV light is much more potent than that by the Fenton reaction, suggesting that the mechanisms of 8-OHdG formation may differ between the two systems. We further compared the antioxidant activities and quenching effect on 8-OHdG formation of genistein with biochanin A. Genistein potently scavenges both hydrogen peroxide in the medium and superoxide anion generated by xanthine/xanthine oxidase, whereas biochanin A has either a weak or no scavenging effect on these reactive oxygen species. However, both genistein and biochanin A display a similar quenching effect on UV light-induced 8-OHdG formation. These results suggest that the quenching effect of genistein and biochanin A on UV light-induced 8-OHdG formation is different from their ability to scavenge hydrogen peroxide and superoxide anion. The potent inhibition of UV light-induced oxidative DNA damage by genistein suggests its potential anticarcinogenic role in photocarcinogenesis.
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PMID:Inhibition of UV light- and Fenton reaction-induced oxidative DNA damage by the soybean isoflavone genistein. 856 40

The exposure of cells to ultraviolet B radiation (UV-B) can induce the production of reactive oxygen species (ROS) which damage cellular components. Free radical scavengers and antioxidants can interfere with the production of ROS. We measured 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, a marker of oxidative DNA damage in rabbit corneal-derived cells (SIRC) exposed to UV-B in the presence of 4-coumaric acid, a natural polyphenol. The levels of 8-OHdG were increased significantly (P<0.01) following irradiation (from 12+/-1.2x10(-6) to 29+/-6.2x10(-6) dG, means+/-SE). When 10 microM 4-coumaric acid was added to the medium, 8-OHdG levels were similar to those of unexposed cells (16.8+/-0.8x10(-6) dG). UV-B irradiation decreased superoxide dismutase (SOD) activity in SIRC cells from 0.29+/-0.6 to 0.15+/-0.04 mU/mg (means+/-SE). The presence of 10 microM 4-coumaric acid prevented the decrease in SOD activity (0.20+/-0.05 mU/mg, P<0.05). On the contrary, SIRC cells exposed to UV-B had higher levels of xanthine oxidase (XO) activity compared with control ones (0.40+/-0.07 and 0.24+/-0.08 mU/mg, means+/-SE, respectively). In the presence of 10 microM 4-coumaric acid, the increase in XO activity was prevented (0.16+/-0.03 mU/mg; mean+/-SE). In conclusion, UV-B-induced oxidative DNA damage in SIRC cells is inhibited by 4-coumaric acid, which, probably through its free radical scavenging activity, stabilizes SOD activity and blocks the increase of XO activity following UV-B irradiation. Thus, the topical use of 4-coumaric acid may prevent free radical damage in the cornea.
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PMID:Protection against ultraviolet B-induced oxidative DNA damage in rabbit corneal-derived cells (SIRC) by 4-coumaric acid. 1249 17

The aim of this study was to test the effect of antioxidant supplementation on enzymatic abnormalities and free radical-modified DNA adducts associated with premalignant changes in the gastric mucosa of elderly patients with HP-negative atrophic gastritis (CAG). Sixty patients with atrophic gastritis and intestinal metaplasia underwent a nutritional interview and a gastroscopy with multiple biopsy samples in the antrum that were processed for histology and for assaying: alpha-tocopherol, MDA, xanthine oxidase (XO), ornithine decarboxylase (ODC), and 8-OHdG. Patients were randomly allocated into three matched groups and supplemented for 6 months with (1) vitamin E, 300 mg/day; (2) multivitamin, two tablets t.i.d.; and (3) Immun-Age 6 g/day nocte (ORI, Gifu, Japan), a certified fermented papaya preparation with basic science-validated antioxidant/immunomodulant properties. Ten dyspeptic patients served as controls. Histology and biochemistry were blindly repeated at 3 and 6 months. CAG patients showed a significantly (P <.05) increased level of mucosal MDA and XO concentration that were reverted to normal by each supplementation (P <.05). All supplements caused a significant decrease of ODC (P <.01), but Immun-Age yielded the most effective (P < 0.05) and was the only one significantly decreasing 8-OhdG (P < 0.05). These data suggest that antioxidant supplementation, and, namely, Immun-Age, might be potential chemopreventive agents in HP-eradicated CAG patients and especially in the elderly population.
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PMID:The aging/precancerous gastric mucosa: a pilot nutraceutical trial. 1524 13

Oxidative stress has been associated with Down syndrome (DS) and with its major phenotypic features, such as early ageing. In order to evaluate an in vivo pro-oxidant state, the following analytes were measured in a group of DS patients aged 2 months to 57 years: (a) leukocyte 8-hydroxy-2'-deoxyguanosine (8-OHdG); (b) blood glutathione; (c) plasma levels of: glyoxal (Glx) and methylglyoxal (MGlx); some antioxidants (uric acid, UA, ascorbic acid, AA and Vitamin E), and xanthine oxidase (XO) activity. A significant 1.5-fold increase in 8-OHdG levels was observed in 28 DS patients vs. 63 controls, with a sharper increase in DS patients aged up to 30 years. The GSSG:GSH x 100 ratio was significantly higher in young DS patients (< 15 years), in contrast to DS patients aged >or=15 years that showed a significant decrease in the GSSG:GSH x 100 ratio ratio vs. controls of the respective age groups. Plasma Glx levels were significantly higher in young DS patients, whereas no significant difference was detected in DS patients aged >or=15 years. Unlike Glx, the plasma levels of MGlx were found to be significantly lower in DS patients vs. controls. A significant increase was observed in plasma levels of UA in DS patients that could be related to an increased plasma XO activity in DS patients. The plasma concentrations of AA were also increased in young (< 15 years) DS patients, but not in older patients vs. controls in the same age range. The levels of Vitamin E in DS patients did not differ from the values determined in control donors. The evidence for a multiple pro-oxidant state in young DS patients supports the role of oxidative stress in DS phenotype, with relevant distinctions according to patients' ages.
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PMID:Multiple evidence for an early age pro-oxidant state in Down Syndrome patients. 1661 64

Oxidative and nitrosative stress are known to exert various adverse effects on biological systems and this seems to be one of the major contributor of nephrotoxicity induced by cyclosporine A (CsA), which is a major clinical challenge, despite its potent immunosuppressive effect. Sulphated polysaccharides of marine origin are well known for its antioxidant properties, among its other biological applications. CsA administration (25 mg/kg body weight, orally, for 21 d) showed increased level of oxidants and xanthine oxidase activity. CsA induced nitrosative stress was evident from a marked elevation in the expression of inducible nitric oxide synthase mRNA in renal tissue and a concomitant increase in plasma nitric oxide level. Augmented levels of malondialdehyde, 8-hydroxy-2-deoxyguanosine and protein carbonyl coupled with diminished protein thiols; hallmarks of lipid peroxidation, DNA damage and protein oxidation were noted in CsA administered rats. Membrane damage was further confirmed by altered ATPase activities in the renal tissue. Simultaneous treatment with sulphated polysaccharides (5 mg/kg body weight, subcutaneously) remarkably prevented the above alterations mediated by oxidative and/or nitrosative stress during CsA induction. Hence, these findings conclude that the use of an antioxidant agent like sulphated polysaccharides could be a useful tool in reducing CsA-induced nephrotoxicity.
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PMID:Oxidative and nitrosative stress mediated renal cellular damage induced by cyclosporine A: role of sulphated polysaccharides. 1760 63

Several dietary flavonoids such as quercetin, luteolin and genistein have been suggested to have cancer chemopreventive effects, although the mechanisms are not fully understood. In the present study, the effects of these flavonoids as antioxidants were investigated in the following systems: (1) production of hydrogen peroxide (H2O2) and superoxide anion (O2*-), (2) lipid peroxidation induced by FeCl2 in rat liver, and (3) formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) induced by either UV or Fenton reaction in calf thymus DNA. The results showed that quercetin and luteolin were equally potent in scavenging H2O2, with genistein having a moderate effect. Quercetin and luteolin had a potent inhibitory effect on O2*- generation by xanthine/xanthine oxidase while genistein had a moderate effect. Quercetin and luteolin were potent in inhibiting lipid peroxidation induced by FeCl2 in rat liver while genistein had a very weak inhibitory effect. All the test compounds had a potent quenching effect on 8-OHdG formation induced by UV light irradiation, with the order of effects being genistein > luteolin > quercetin. Of the test compounds, luteolin exhibited the most potent quenching effect on Fenton-induced 8-OHdG formation. The scavenging of oxygen free radicals, the inhibitory effect on lipid peroxidation and the quenching effect on 8-OHdG formation by quercetin, luteolin and genistein may, at least in part, be responsible for their anticarcinogenic effects.
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PMID:Dietary flavonoids, quercetin, luteolin and genistein, reduce oxidative DNA damage and lipid peroxidation and quench free radicals. 1837 28

The aims of the present study were to determine the level of oxidative stress and the salient factors leading to the relapse of acute myeloid leukemia (AML). Oxidative stress-related parameters and the expressions of specific genes were monitored in 102 cases of AML during a pretreatment period from a primary status to a relapse status. In addition, age-matched healthy subjects were classified as controls. The activities of adenosine deaminase and xanthine oxidase were higher in the relapse condition, whereas those of glutathione peroxidase, monoamine oxidase, and superoxide dismutase, and the total antioxidant capacity (T-AOC) were lower in the primary condition and in controls. Of particular note, levels of advanced oxidation protein products, malondialdehyde, and 8-hydroxydeoxyguanosine were also significantly higher in relapse patients. Furthermore, real-time PCR with SYBR Green revealed that the expression levels of human thioredoxin (TRX) and indoleamine 2,3-dioxygenase were increased in relapse patients. Pearson correlation analysis revealed that the T-AOC was positively correlated with GSH but negatively correlated with 8-OHdG, TRX, and indoleamine 2,3-dioxygenase. Linear regression showed that a low T-AOC and up-regulated TRX expression were the independent factors correlated with relapse. A strong association between oxidative stress and the incidence of disease relapse was observed, which has potential prognosis implications. These results indicate that oxidative stress is a crucial feature of AML and probably affects the development and relapse of AML.
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PMID:Involvement of oxidative stress in the relapse of acute myeloid leukemia. 2023 20

Placental oxidative stress plays a key role in the pathophysiology of placenta-related disorders, most notably preeclampsia (PE) and intrauterine growth restriction (IUGR). Oxidative stress occurs when accumulation of reactive oxygen species (ROS) damages DNA, proteins and lipids, an outcome that is limited by antioxidant enzymes; mitochondrial uncoupling protein 2 (UCP2) may also limit oxidative stress by reducing ROS production. Here we characterized placental antioxidant defenses during normal gestation and following glucocorticoid-induced IUGR. Placentas were collected on Days 16 and 22 of normal rat pregnancy (term = Day 23) and at Day 22 after dexamethasone treatment from Day 13. Expression of several genes encoding antioxidant enzymes (Sod1, Sod2, Sod3, Cat, Gpx3, Txn1, Txnrd1, Txnrd2, and Txnrd3) and Ucp2 was measured by quantitative RT-PCR in the labyrinth (LZ) and junctional zones (JZ) of the placenta. Expression of Sod1 and Ucp2 mRNAs and the activity of xanthine oxidase, a source of ROS, all increased from Days 16 to 22 in both placental zones, whereas Sod2 and Gpx3 increased only in the rapidly growing LZ. In contrast, Sod3 and Txnrd1 expression fell in the LZ over this period, whereas total superoxide dismutase activity remained stable. Dexamethasone treatment reduced fetal-placental growth and LZ expression of Ucp2 but increased JZ expression of Txn1. Indices of placental oxidative damage (TBARS, F(2)-isoprostanes, and 8-OHdG) did not change with gestational age or dexamethasone, indicative of adequate antioxidant protection. Overall, our data suggest that the rat placenta is protected from oxidative stress by the dynamic zone- and stage-dependent expression of antioxidant defense genes.
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PMID:Antioxidant defenses in the rat placenta in late gestation: increased labyrinthine expression of superoxide dismutases, glutathione peroxidase 3, and uncoupling protein 2. 2039 69

This paper reviews the body of evidence that major depression is accompanied by a decreased antioxidant status and by induction of oxidative and nitrosative (IO&NS) pathways. Major depression is characterized by significantly lower plasma concentrations of a number of key antioxidants, such as vitamin E, zinc and coenzyme Q10, and a lowered total antioxidant status. Lowered antioxidant enzyme activity, e.g. glutathione peroxidase (GPX), is another hallmark of depression. The abovementioned lowered antioxidant capacity may impair protection against reactive oxygen species (ROS), causing damage to fatty acids, proteins and DNA by oxidative and nitrosative stress (O&NS). Increased ROS in depression is demonstrated by increased levels of plasma peroxides and xanthine oxidase. Damage caused by O&NS is shown by increased levels of malondialdehyde (MDA), a by-product of polyunsaturated fatty acid peroxidation and arachidonic acid; and increased 8-hydroxy-2-deoxyguanosine, indicating oxidative DNA damage. There is also evidence in major depression, that O&NS may have changed inactive autoepitopes to neoantigens, which have acquired immunogenicity and serve as triggers to bypass immunological tolerance, causing (auto)immune responses. Thus, depression is accompanied by increased levels of plasma IgG antibodies against oxidized LDL; and increased IgM-mediated immune responses against membrane fatty acids, like phosphatidyl inositol (Pi); oleic, palmitic, and myristic acid; and NO modified amino-acids, e.g. NO-tyrosine, NO-tryptophan and NO-arginine; and NO-albumin. There is a significant association between depression and polymorphisms in O&NS genes, like manganese superoxide dismutase, catalase, and myeloperoxidase. Animal models of depression very consistently show lowered antioxidant defences and activated O&NS pathways in the peripheral blood and the brain. In animal models of depression, antidepressants consistently increase lowered antioxidant levels and normalize the damage caused by O&NS processes. Antioxidants, such as N-acetyl-cysteine, compounds that mimic GPX activity, and zinc exhibit antidepressive effects. This paper reviews the pathways by which lowered antioxidants and O&NS may contribute to depression, and the (neuro)degenerative processes that accompany that illness. It is concluded that aberrations in O&NS pathways are--together with the inflammatory processes--key components of depression. All in all, the results suggest that depression belongs to the spectrum of (neuro)degenerative disorders.
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PMID:A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. 2047 44


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