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)

This study was planned to define the metabolic pathways for free radical production by isolated glomeruli and glomerular epithelial cells in vitro after exposure to cytotoxic doses of doxorubicin. A net increment in glomerular superoxide anion (O2.) synthesis was observed at doxorubicin doses between 10 and 30 micrograms/ml, a drug level which also induced a parallel increment in uric acid synthesis. Since the synthesis of O2. with production of uric acid implies an activity of xanthine oxidase, a few experiments were performed with glomeruli which had been deprived of xanthine oxidase activity. In this case doxorubicin-inducible O2. and uric acid synthesis by glomeruli was practically nil. A similar stimulatory effect of O2. synthesis was induced by doxorubicin on glomerular epithelial cells and also in this case O2. synthesis was suppressed by pre-treating cells with deoxyconformicin, a selective inhibitor of adenosine deaminase. Finally, equimolar amounts of the drug were equally cytotoxic even when kept constantly outside the cell by a stable linkage with an agarose macroporous bed. In summary, these data demonstrate that O2. is generated by isolated glomeruli and glomerular epithelial cells 'in vitro' when exposed to cytotoxic amounts of doxorubicin and that purine degradation to uric acid furnish the metabolic pathways for glomerular O2. generation. However, doxorubicin is comparably cytotoxic on glomerular epithelial cells from outside cells thus suggesting that also a membrane perturbation may activate the series of events leading to cell injury.
Eur J Pharmacol 1992 Sep 01
PMID:Multiple mechanisms for doxorubicin cytotoxicity on glomerular epithelial cells 'in vitro'. 133 79

The biochemical mechanisms underlying blood lymphoid cell genome destabilization in patients with HIV infection have been analyzed. Lymphocytes from HIV patients are characterized by increasing intensity of free radical oxidation together with activation of the xanthine oxidase D-form conversion into the O-form, enhanced activity of UV-endonuclease, and intensification of prooxidant-induced proteolysis. These changes increasing with the progress of the disease with a maximum at the AIDS stage form a metabolic basis for labilization of the lymph cell genome. The degree of biochemical manifestations of genome instability (levels of chromatin degradation products and intensity of formation of one-filament nicks of DNA) increase in the dynamics of HIV-infection. The data obtained are discussed in terms of the author's conception on the origin of AIDS from retroposons (retrotransposons?). A hypothesis is postulated on accumulation of autonomous genetic information on the basis of genome labilization under the influence of genotoxic factors. Clinico-biochemical data on the appearance of HIV proteins (p17, p24) in the blood of patients (previously negative for all HIV markers) in the presence of transfusions of HIV-negative blood and UV-irradiation of the autoblood are also discussed from this standpoint.
Biokhimiia 1992 Sep
PMID:[Genomic instability and AIDS]. 133 9

We studied the activities of xanthine dehydrogenase and xanthine oxidase in rat forebrain after complete ischaemia. Complete ischaemia was induced by decapitation after transcardiac infusion with saline. The activities of xanthine dehydrogenase and xanthine oxidase immediately after ischaemia were 93.3 +/- 38.7 and 18.8 +/- 7.7 microU/mg protein, respectively, and at 24 h after ischaemia were 183.5 +/- 75.1 and 60.8 +/- 15.2 microU/mg protein, respectively. The ratios of xanthine dehydrogenase/xanthine oxidase immediately and 24 h after ischaemia were 5.04 +/- 1.03 and 3.04 +/- 0.99, respectively. These data indicate that xanthine dehydrogenase and xanthine oxidase activities were maintained even 24 h after complete ischaemia. Conversion of xanthine dehydrogenase to xanthine oxidase proceeds slowly during complete ischaemia.
Neurol Res 1992 Sep
PMID:Change of xanthine dehydrogenase and xanthine oxidase activities in rat brain following complete ischaemia. 136 Jun 27

Three factorial experiments were conducted to determine if high dietary fluoride (F) would inhibit selenite toxicity in rats. Initially, three levels of selenite (0.05, 3, and 5 mg/kg diet) were matched against three levels of F (2, 75, and 150 mg/kg diet). Fluoride failed to prevent the depressive effect of selenite on 8-wk food intake and body wt gain. Selenium (Se) concentration of plasma and kidney and enzymatic activity of whole blood glutathione peroxidase (GSH-Px) were also unaffected by F. Liver Se concentration, however, was slightly (12%) but significantly (p < 0.025) reduced when the highest F and Se levels were combined. Fluoride (150 mg/kg) appeared to reduce liver selenite toxicity (5 mg/kg). Therefore, further study focused on liver histology with treatments that eliminated the middle levels of selenite and F. Fluoride prevented the hepatic necrosis seen in selenite-toxic rats. Similar histological lesions were not observed for kidney or heart. Fluoride partially (26%) but significantly (p < 0.025) reduced thiobarbituric-reactive substances in selenite-toxic rats, but there was no F effect on intracellular distribution of liver Se, glutathione levels in liver and kidney, or on liver xanthine oxidase activity. Overall, the protective effect of F on selenite toxicity appears to be confined to liver pathology. The exact mechanism for this effect, however, remains unclear.
Biol Trace Elem Res 1992 Sep
PMID:Effect of dietary fluoride on selenite toxicity in the rat. 138 17

Caffeine is sequentially metabolized by cytochrome P4501A2 (CYP1A2), N-acetyltransferase (NAT) and/or xanthine oxidase (XO). In the present study the activity of these three enzymes was estimated from ratios of the metabolites formed from dietary caffeine and excreted into the urine collected as spot samples. In the urine samples from 10 out of 377 subjects concentrations of caffeine metabolites were too low to allow reliable measurements of the ratios. In 335 healthy subjects the NAT activity showed a typically bimodal distribution with 47% fast acetylators and 53% slow acetylators, consistent with a Danish population. The ratios reflecting CYP1A2 and XO activities were log normal and normal distributed, respectively. In 103 non-smoking men and 90 non-smoking women the ratio of caffeine metabolites expressing CYP1A2 activity was 4.7 +/- 1.6 and 4.3 +/- 1.9 as compared to 7.8 +/- 2.5 and 7.3 +/- 3.0 in 31 male and 25 female subjects smoking 10 cigarettes/day or more respectively, verifying induction of CYP1A2 by tobacco (P less than 0.05), but minimal sex-related differences. In 12 non-smoking pregnant women and in 28 women using oral contraceptives the CYP1A2 ratio was 29 and 20% reduced respectively (P less than 0.05). In a multivariate analysis the only significant predictor of the XO ratio was the consumption of caffeine with an increase of 2% per cup of coffee or equivalent (P less than 0.05). In 23 healthy male subjects 30 days of vigorous exercise increased the CYP1A2 ratio by 70% and the XO ratio by 42% (P less than 0.05), but left the NAT ratio unchanged. In nine healthy volunteers daily ingestion of 500 g of broccoli for 10 days increased the CYP1A2 ratio by an average of 12% (P less than 0.05), compared to a control period with ingestion of an equivalent weight of non-cruciferous green vegetables. The ratios of metabolites from dietary caffeine in spot urine samples offer ethical, non-invasive and reliable estimates of CYP1A2, NAT and XO. These enzymes are highly relevant for the bioactivation of potentially toxic compounds and the formation of oxygen radicals. The method is applicable in large-scale epidemiological studies, allowing, for example, prospective testing of the relationship between these enzyme activities and the development of disease. Exercise may increase CYP1A2 activity to a magnitude corresponding to heavy smoking, as well as XO by mechanisms that remain to be clarified.
Carcinogenesis 1992 Sep
PMID:Foreign compound metabolism capacity in man measured from metabolites of dietary caffeine. 139 40

The effects of reactive oxygen species (ROS) on cultured rat mesangial cells were studied by measuring planar cell surface area (PCSA) after incubation with xanthine plus xanthine oxidase (XXO), in the presence of superoxide dismutase (SOD; 5 micrograms/ml) or catalase (CAT; 20 micrograms/ml), or after incubation with H2O2. Myosin light chain (MLC) phosphorylation was assessed in cells prelabeled with o-[32P]phosphoric acid and incubated with H2O2, after protein separation with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A possible intermediate role for platelet-activating factor (PAF) was analyzed by preincubation of the cells with a PAF antagonist BN 52021 (BN, 5 x 10(-5) M) and by measuring PAF-specific [3H]acetate incorporation and immunoassayable PAF. XXO significantly decreased PCSA (14%), an effect abolished by CAT but not by SOD. H2O2 induced a similar effect, in a dose-dependent and time-dependent manner. MLC phosphorylation increased by 81 +/- 15% after H2O2 incubation, and this effect was blocked by BN. BN also completely blocked the effect of H2O2 on PCSA. PAF-specific [3H]acetate incorporation increased in the presence of H2O2 (from 6,886 +/- 2,030 to 58,703 +/- 16,063 counts.min-1.mg-1) as well as the immunoassayable PAF production by cells (from 0.90 +/- 0.19 to 6.71 +/- 2.27 ng/mg). These results suggest that ROS, particularly H2O2, could modulate the surface area of mesangial cells, modifying the ultrafiltration coefficient, thus explaining the decrease in glomerular filtration rate in those pathological situations characterized by an increased ROS synthesis. PAF could be involved in the genesis of these effects.
Am J Physiol 1992 Sep
PMID:Effects of reactive oxygen species on cultured rat mesangial cells and isolated rat glomeruli. 141 75

The interaction between milk xanthine oxidase (XO) and lactoperoxidase (LP) in model system and antimicrobial action of these enzymes on Escherichia coli 0-111 were studied. It was shown, that bacterial superoxide dismutase (SOD), which transforms O2-. (XO-reaction product) into H2O2 (substrate of LP), is necessary for binding of the reaction sequence: XO-->LP-->antimicrobial products. It is suggested, that these enzymes unite in the protective system in intestinal infections of newborns. Bacterial SOD in this case acts as the key factor, creating the system.
Biull Eksp Biol Med 1992 Sep
PMID:[Free-radical mechanism of antimicrobial action of xanthine oxidase and lactoperoxidase]. 147 55

Rat ventricular myocytes have been isolated and cultured by two separate procedures. Using phase-contrast and electron microscopies, we illustrate that (a) definitive cell damage is produced when myocytes are exposed to xanthine oxidase--hypoxanthine and (b) purpurogallin between 0.25 and 1.0 mM prolongs survival of both myocyte preparations in a dose-dependent manner. The cytoprotection produced by 1 mM purpurogallin exceeds that given by 2 mM each of ascorbate, Trolox, and mannitol, or 24,200 IU superoxide dismutase/L and (or) 92,000 IU catalase/L. Furthermore, we noted, for the first time, that purpurogallin markedly protects rat aortic endothelial cells, a key target of free radical generation and attack. In contrast, Trolox has a negligible effect here. Mechanistically, we showed that purpurogallin inhibits urate formation by xanthine oxidase more potently than allopurinol. Also, the compound diminishes formation of superoxide-reduced cytochrome c. Therefore, purpurogallin is a potent protector of ventricular myocytes and aortic endothelial cells, both of which are important cells in the cardiovascular system.
Biochem Cell Biol 1992 Sep
PMID:Purpurogallin protects both ventricular myocytes and aortic endothelial cells of rats against oxyradical damage. 148 57

Hyperoxia has been suggested as a risk factor for kernicterus. The toxicity of hyperoxia may be mediated by free radicals. We investigated the effects of free radicals, formed by the hypoxanthine/xanthine oxidase system, with and without additional hyperoxia, on the accumulation of bilirubin and albumin in rat brain. Hypoxanthine was infused for 60 min into retrograde carotid catheters in awake, young, male SPRD rats. After 30 min the infusion was briefly interrupted to inject xanthine oxidase 1 U/kg through the same catheter. Group I (controls) received 0.9% NaCl in lieu of hypoxanthine/xanthine oxidase. Groups I and II breathed room air at all times, while group III breathed 90% O2. After 60 min all groups received a bolus dose of 125I-albumin through a peripheral venous catheter, followed by bilirubin 25 mg/kg for 5 min, then bilirubin 35 mg/kg for 55 min. There were no significant differences between the groups as regards serum bilirubin, serum albumin, brain bilirubin, or brain albumin. Neither during normoxic nor hyperoxic conditions did the hypoxanthine/xanthine oxidase system increase the accumulation of bilirubin or albumin in rat brain.
Early Hum Dev 1992 Sep
PMID:The effects of hypoxanthine, xanthine oxidase and hyperoxia on the accumulation of bilirubin and albumin in young rat brain. 149 69

Intralobular heterogeneity of oxidative stress and its topographic relationship with cell death during low-flow hypoxia were shown in perfused rat liver by digital microfluorography using dichlorofluorescin diacetate, a fluorochrome sensitive to intracellular hydroperoxide formation, and propidium iodide, which labels the nuclei of nonviable cells. The surface of the liver loaded with two precursors was microscopically visualized, and the fluorescence of dichlorofluorescein, a highly fluorescent molecule generated by hydroperoxide-mediated dichlorofluorescin oxidation, was digitally processed. Dichlorofluorescein fluorescence significantly increased in midzonal regions as early as 20 minutes after starting the 25% low-flow hypoxia. At 40 minutes the fluorograph showed multiple dotted patterns, and the intensity peaked at 60 minutes. The onset of cell death studied by propidium iodide was observed at 40 minutes, and its topographic distribution corresponded to the dichlorofluorescein-enhanced midzonal regions. Allopurinol diminished the early midzonal oxidative stress and retarded the onset of cell death. The current findings show that xanthine oxidase-dependent oxidative stress and the resultant cell death during low-flow hypoxia are spatially restricted in the intermediate zone between the periportal and pericentral regions.
Gastroenterology 1992 Sep
PMID:Early midzonal oxidative stress preceding cell death in hypoperfused rat liver. 149 48


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>