Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven flavonoids and three non-flavonoid antioxidants, i.e. butylated hydroxyanisole, chlorpromazine and BW 755 C, were studied as potential scavengers of oxygen free radicals. Superoxide anions were generated enzymatically in a xanthine-xanthine oxidase system and non-enzymatically in a phenazine methosulphate-NADH system, and assayed by reduction of nitro blue tetrazolium. The generation of malonaldehyde (MDA) by the ascorbate-stimulated air-oxidised boiled rat liver microsomes was considered as an index of the non-enzymatic formation of hydroxyl radicals. Flavonoids but not non-flavonoid antioxidants lowered the concentration of detectable superoxide anions in both enzymic and non-enzymic systems which generated these SOD-sensitive radicals. The most effective inhibitors of superoxide anions were quercetin, myricetin and rutin. Four out of seven investigated flavonoids seemed also to suppress the activity of xanthine oxidase as measured by a decrease in uric acid biosynthesis. All ten investigated compounds inhibited the MDA formation by rat liver microsomes. Non-flavonoid antioxidants were more potent MDA inhibitors than flavonoids. It is concluded that antioxidant properties of flavonoids are effected mainly via scavenging of superoxide anions whereas non-flavonoid antioxidants act on further links of free radical chain reactions, most likely by scavenging of hydroxyl radicals.
 ...
PMID:Flavonoids are scavengers of superoxide anions. 283 Aug 82

Isolated erythrocyte membranes exposed to protease-free xanthine oxidase plus xanthine and ferric iron undergo lipid peroxidation and protein crosslinking (appearance of high molecular weight aggregates on sodium dodecyl sulfate (SDS) gel electrophoresis). Spectrin is more susceptible to crosslinking than the other polypeptides. Thiol-reducible bonds (disulfides) as well as nonreducible bonds are generated, the former type relatively rapidly (detected within 10-20 min) and the latter type more slowly (usually detected after 1 h). Reducible crosslinking is inhibited by catalase, but not by superoxide dismutase, desferrioxamine, butylated hydroxyltoluene, and mannitol; whereas nonreducible crosslinking, like free radical lipid peroxidation, is inhibited by all of these agents except mannitol. Zinc(II) also inhibits lipid peroxidation, but stimulates disulfide bond formation to the virtual exclusion of all other crosslinking. Our results indicate that disulfide formation is dependent on H2O2, but not O2- or iron. However, O2-, H2O2, and iron are all required for lipid peroxidation and nondisulfide crosslinking, suggesting the intermediacy of OH generated via the iron-catalyzed Haber-Weiss reaction. The possible role of malonaldehyde (MDA, a by-product of lipid peroxidation) in the latter type of crosslinking was examined. Solubilized samples of xanthine/xanthine oxidase-treated membranes showed a strong visible fluorescence (emission maximum 450 nm; excitation 390 nm). This resembled the fluorescence of membranes treated with authentic MDA, which forms conjugated imine linkages between amino groups. Fluorescence scanning of SDS gels from MDA-treated membranes showed a strong signal coincident with crosslinked proteins and also one in the low molecular weight, nonprotein region, suggestive of aminolipid conjugates. Similar scanning on xanthine/xanthine oxidase-reacted membranes indicated that all fluorescence is associated with the lipid fraction. Thus, nonreducible protein crosslinks in this system do not appear to be of the MDA-derived, Schiff base type.
 ...
PMID:Xanthine oxidase-catalyzed crosslinking of cell membrane proteins. 380 Mar 91

The antioxidant activity of nimesulide and its main metabolites, 4'-hydroxynimesulide (M1) and 2-(4'-hydroxyphenoxy)-4-N-acetylamino-methansulfonanilide (M2), was investigated using 2 in vitro models: NADPH-supported lipid peroxidation in rat liver microsomes (marker MDA formation) and xanthine/xanthine oxidase, iron-promoted depolymerisation of hyaluronic acid, determined by gel permeation chromatographic analysis (marker molecular weight distribution). In the lipid peroxidation model, all the compounds inhibited MDA formation in a concentration-dependent manner, although with different potencies; the maximum scavenging effect was observed for M1 [50% inhibitory concentration (IC50) = 30 mumol/L; M2 IC50 = 0.5 mmol/L; nimesulide = 0.8 mmol/L]. Nimesulide was more active than its metabolites in preventing OH-induced depolymerisation of hyaluronic acid, with a 50% effective concentration of approximately 230 mumol/L, which was fairly comparable to that of tenoxicam. This protective effect was due to the OH.-entrapping capacity of the drug, which, in the Fenton-driven model, is easily converted, via OH. attack, to M1 and putatively to 2-hydroxy-4-nitro-methansulfonanilide.
 ...
PMID:Antioxidant activity of nimesulide and its main metabolites. 750 57

In this study, calf aortic endothelial cells (ECs) were cultured in vitro to study the ECs damages induced by exogenous oxygen free radical (OFR), and the protective effects of ginsenosides. Exogenous OFR was generated by three methods: enzyme reaction (xanthine-xanthine oxidase), chemical reaction (Cu(2+)-ascorbate) and electrolysis. The experimental results indicated that the xanthine-xanthine oxidase method is most suitable for the study of free radical mediated ECs damages. Addition of ginsenosides (40 microliters.ml-1) reduced the concentration of MDA in the cultured ECs, while the 6-keto-PGF1 alpha content in the medium was reduced (P > 0.05) and the morphologic damages of the ECs was alleviated. It is concluded that ginsenosides exerted a protective effects on ECs damages against lipid peroxidation, and ginsenosides might play an important role in antiatherosclerosis through its protective effect on endothelial cells.
 ...
PMID:[Protective effects of ginsenosides on oxygen free radical induced damages of cultured vascular endothelial cells in vitro]. 786 80

In the present study, it was observed that somatostatin could significantly protect rat gastric mucosa from injury induced by cold-restraint stress and inhibit the stress induced increase of malonaldehyde (MDA) content. In the gastric mucosa of stress rats, the xanthine oxidase (XO) activity were increased and the glutathione peroxidase (GSH-Px) activity were decreased respectively, while the superoxide dismutase (SOD) activity showed no change. After pretreatment with somatostatin, the decrease of GSH-Px activity was significantly reversed, whereas XO and SOD activities were not significantly affected. The above results show that the protective effect of somatostatin against the stress-induced injury of gastric mucosa may be related to an enhancement of the ability of gastric mucosa to scavenge oxygen-derived free radicals.
 ...
PMID:[Protective effect of somatostatin against stress injury of gastric mucosa may be related to the scavenge of free radicals]. 797 28

Lipid peroxidation (LPO) is the oxidative deterioration of polyunsaturated fatty acids (PUFA) with the production of lipid hydroperoxides, cyclic peroxides, cyclic endoperoxides, and finally fragmentation to ketones and aldehydes (including malonaldehyde, MDA). Estimation of LPO through MDA formation measured by assaying thiobarbituric acid (TBA) reactive products remains the method of choice to study the development of oxidative stress in tissues. However, MDA estimation by TBA reactive products is non-specific and often gives erroneous results. In this report we describe a method using high-performance liquid chromatographic separation to estimate MDA, formaldehyde (FDA), acetaldehyde (ADA), acetone, and propionaldehyde (PDA), the degradation products of oxygen-derived free radicals (ODFR) and PUFA, as presumptive markers for LPO. Oxidative stress was induced in the tissue by perfusing an isolated rat heart with hydroxyl radical generating system (xanthine + xanthine oxidase + FeCl3 + EDTA). The coronary effluents were collected, derivatized with 2,4-dinitrophenylhydrazine (DNPH), and extracted with pentane. Aliquots of 25 microliters in acetonitrile were injected onto a Beckman Ultrasphere C18 (3 microns) column. The products were eluted isocratically with a mobile phase containing acetonitrile-water-acetic acid (40:60:0.1, v/v/v), measured at three different wavelengths (307, 325 and 356 nm) using a Waters M-490 multichannel UV detector and collected for gas chromatography-mass spectrometry (GC-MS) analysis. The peaks were identified by cochromatography with DNPH derivatives of authentic standards, peak addition, UV pattern of absorption at the three wavelengths, and by GC-MS. The retention items of MDA, FDA, ADA, acetone, and PDA were 5.3, 6.6, 10.3, 16.5, and 20.5 min, respectively. The results of our study indicated progressive increase of all five lipid metabolites as a function of the duration of ODFR perfusion. Hydroxyl radical scavengers, superoxide dismutase plus catalase, completely inhibited the formation of these lipid metabolites, demonstrating that the release of lipid metabolites from the isolated heart was indeed in response to oxidative stress. Since MDA, FDA, ADA, acetone, and PDA are the products of ODFR-PUFA interactions, this method allows proper estimation of LPO which monitors the oxidative stress developed during the reperfusion of ischemic myocardium.
 ...
PMID:High-performance liquid chromatographic method for the simultaneous detection of malonaldehyde, acetaldehyde, formaldehyde, acetone and propionaldehyde to monitor the oxidative stress in heart. 813 6

The aim of this study was to set up a simple procedure for assessing lipid peroxidation (L.P.) and testing the activity of antioxidant compounds. L.P. was determined in rat brain homogenates by measuring the endogenous and stimulated accumulation of malonaldehyde (MDA). MDA was assayed by an HPLC method. Homogenates spontaneously formed appreciable amounts of MDA. The addition of increasing concentrations of FeCl2 resulted in a linear accumulation of MDA, up to 16.6-fold at 50 microM. An organic form of iron (Fe-saccharate) was less active on MDA formation (11.4-fold increase at 100 microM). The addition of xanthine-xanthine oxidase resulted in only a 2.4-fold increase in MDA formation. Various antioxidant or chelating compounds effectively inhibited L.P., with IC50 between 0.1 microM (phenoxazine) and 4-50 microM (alpha-tocopherol). Their potencies depended on the iron concentration and time of preincubation with the homogenates. In conclusion, this is a simple and reliable procedure for studying L.P. and inhibiting agents, provided that the experimental conditions are carefully assessed.
 ...
PMID:Studies on lipid peroxidation in the rat brain. 817 67

In the present investigation alterations in the free radical generating and scavenging enzymes in platelets, neutrophils (PMNLs), heart and lung homogenates following rat pulmonary thromboembolism have been studied. Thrombosis was induced by intravenous infusion of collagen and adrenaline. Levels of malonaldehyde (MDA) were elevated in the PMNLs after thrombosis. Activities of superoxide dismutase (SOD) and catalase (CAT) were found to increase in platelets and PMNLs respectively. However, there was no significant alteration in the lactate dehydrogenase (LDH), lysozyme (LYS), ratio of xanthine oxidase to dehydrogenase (XO/XH) and PMNLs O2- generation before and after thrombosis. Migration of PMNLs following thrombosis was indicated by increased activity of myeloperoxidase (MPO) in the heart. In addition, pretreatment with allopurinol, a xanthine oxidase inhibitor and indomethacin, a cyclooxygenase inhibitor offered protection against thromboembolism induced death/paralysis. Results suggest the involvement of free radicals in thrombosis.
 ...
PMID:Free radical scavenging mechanisms during pulmonary thromboembolism in rats. 846 69

Prolonged hypoxia induced transient drug resistance in Chinese hamster lung fibroblasts. Previously hypoxic cells were resistant to adriamycin and resistant to etoposide. Complete recovery of etoposide sensitivity was observed following reaeration for 24 hr. A change in P-glycoprotein expression was unlikely to contribute to the resistance caused by hypoxia, since adriamycin resistance was not reversed by verapamil. However, alteration in the plasma membrane structure may be involved, since previously hypoxic cells were resistant to extracellular superoxide radical generated by the addition of xanthine/xanthine oxidase. In contrast, adriamycin sensitivity was not altered by hypoxia in 3 human breast-cancer cell lines. MDA-468 and MCF-7/Adr differed in their response to EGF, independent of the presence of hypoxia. These results suggest that hypoxic-stress-induced drug resistance is not generalized.
 ...
PMID:The effect of hypoxia on acquired drug resistance and response to epidermal growth factor in Chinese hamster lung fibroblasts and human breast-cancer cells in vitro. 851 57

Iron catalyzed free radical formation and lipid peroxidation are accepted mechanisms of heme protein-induced acute renal failure. However, the source(s) of those free radicals which trigger lipid peroxidation in proximal tubular cells remains unknown. This study tested the potential involvement of mitochondrial electron transport, xanthine oxidase activity, and arachidonic acid metabolism in the heme-induced peroxidative state. The impact of cytosolic Ca2+ loading also was assessed. Rhabdomyolysis was induced in mice by glycerol injection, and two hours later heme-laden proximal tubular segments (PTS) were isolated for study. PTS from normal mice served as controls. During 30 to 60 minute incubations, heme loaded PTS developed progressive cytotoxicity (LDH release) and iron-dependent lipid peroxidation (malondialdehyde, MDA, generation; inhibited by deferoxamine). Site 2 (antimycin A) or site 3 (cyanide, hypoxia) mitochondrial respiratory chain inhibition completely blocked lipid peroxidation, whereas site 1 inhibition (rotenone) doubled its extent (presumably by shunting NADH through NADH dehydrogenase, a free radical generating system). Conversely, these agents did not substantially alter MDA in normal PTS. Normal and heme loaded PTS developed comparable degrees of LDH release during respiratory blockade irrespective of increased or decreased MDA production (indicating that lipid peroxidation was not a critical determinant of cell death). Neither increasing free arachidonic acid (PLA2 treatment) nor adding cyclooxygenase/lipoxygenase/cytochrome p450 inhibitors conferred a consistent protective effect. Altering free Ca2+ status (chelators; ionophore addition) and xanthine oxidase inhibition had no discernible impacts. Despite mitochondrial free radical production, mitochondrial function, as assessed by the ATP/ADP ratio, seemingly remained intact. In conclusion, (1) the terminal mitochondrial respiratory chain is the dominant source of free radicals which trigger PTS lipid peroxidation; (2) iron is a required secondary factor; (3) although mitochondria fuel lipid peroxidation, they do not appear to be critical targets of the heme-induced oxidant attack.
 ...
PMID:Mitochondrial free radical production induces lipid peroxidation during myohemoglobinuria. 864 15


<< Previous 1 2 3 4 5 6 7 Next >>