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)

Cyclic AMP (cAMP) is a key intracellular second messenger which at increased levels has been shown to have anti-inflammatory and tissue-protective effects. Its concentration is determined by the activities of both adenylate cyclase (AC) and the phosphodiesterase (PDE) enzymes. The aim of this study was to compare the effects of increased cAMP and glucocorticoid dexamethasone administration on B. melitensis-induced lipid peroxidation, Brucella suppressed antioxidant enzyme activities and PDE4 transcripts in rats. Intracellular cyclic AMP level was elevated by two different approaches; activation of AC and inhibition of PDE activities. Rats were inoculated with B. melitensis for seven days then a single dose of nonselective PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX), the adenylate cyclase activator forskolin and dexamethasone were administrated to each infected group, and animals were challenged for 48 h. Brucella-induced lipid peroxidation was significantly reduced by the cAMP elevating agents as well as dexamethasone administration in plasma, liver and spleen. The antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were significantly decreased by the pathogen. Whilst suppressed GSH-Px activity was reversed by cAMP elevating agents, SOD activity was not restored. Superoxide generating enzyme xanthine oxidase activity was not altered at the end of the infection period. Brucella infection increased plasma IL-12 level and this effect was also suppressed by the cAMP elevating agents, whereas TNF-alpha, IFN-gamma and IL-10 levels were unchanged. Intracellular cAMP levels are entirely hydrolyzed by cAMP-specific PDE 4 isozymes (PDE4s) in inflammatory and immunocompetent cells. Brucella reduced mRNA transcript levels for PDE4A by 40%, though PDE4B and 4D transcriptions were being unaffected in spleen. It was concluded that B. melitensis infection decreased activity of the antioxidant defence system, induced lipid peroxidation and suppressed PDE4A transcription. Administration of cAMP elevating agents exhibited similar affect with dexamethasone on lipid peroxidation, IL-12 production and antioxidant enzyme activities in Brucella infection.
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PMID:The effects of increased cAMP content on inflammation, oxidative stress and PDE4 transcripts during Brucella melitensis infection. 1739 85

The interaction of exercise training and ethanol on the myocardial antioxidant enzymes and the oxidative stress markers was investigated in the Wistar strain male albino rats. We also tested the interactive effects of exercise training and ethanol on the age-associated free radical production and antioxidant defense system. We found a significant decrease (p<0.05) in the activity levels of superoxide dismutase (SOD) and catalase (CAT) in the myocardium of old rats when compared to young rats by 26% and 58%, respectively, suggesting the onset of age-dependent decrease in the myocardial antioxidant enzyme system. In contrast to the decreased antioxidant enzyme activity, xanthine oxidase (XOD) and lipid peroxidation (LPO) levels were elevated, suggesting the age-induced oxidative stress. Exercise training significantly (p < 0.05) elevated the activities of SOD, CAT, XOD and LPO levels in both the age groups of animals. Ethanol consumption significantly lowered the SOD and CAT activities in both the age groups, whereas a significant increase was observed in the XOD and LPO levels. In contrast, the combination of exercise training plus ethanol lowered XOD and LPO levels in both the age groups of rats compared to ethanol treated rats. A significant (p < 0.05) increase in the activities of SOD and CAT was reported in the rats treated with the combination of exercise training plus ethanol. This increase was more pronounced in the younger rats than the older rats. The findings of the present investigation on the potential role of antioxidant enzymes to counter the ethanol-induced pro-oxidants showed an increase with the interaction of exercise training. With age, a decrease in the antioxidant enzyme capacity was observed. This reveals that the old age rats were more affected to the pro-oxidants when compared to the young age rats. In conclusion it is demonstrated that two months treadmill endurance exercise training is beneficial to both young and old rats in improving antioxidant defense to challenge the oxidative stress in the myocardial tissue and thereby successfully countering the free radical production due to ethanol intoxication.
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PMID:Myocardial antioxidant status and oxidative stress after combined action of exercise training and ethanol in two different age groups of male albino rats. 1758 7

Cadmium (Cd) exposure has been recognized to result in a wide variety of cellular responses, including oxidative stress and body weight loss. The aim of the present study was to examine the effect of lycopene supplementation on the antioxidant defense system, lipid peroxidation (LPO) level, nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha) production, and body weight in Cd-exposed rats. Animals were divided into four groups (n = 7): control, Cd-treated, Cd plus lycopene-treated, and lycopene-treated. Cadmium (as CdCl2) was administrated orally for 20 days (6.6 mg kg(-1) day(-1)), and lycopene (10 mg kg(-1) day(-1)) was similarly administered. Lycopene administration significantly suppressed Cd-induced LPO in plasma and kidney homogenates. Lycopene also reversed Cd-decreased body weight compared to the control. Cadmium treatment had diverse effects on the antioxidant enzyme activities. Although antioxidant superoxide dismutase activity was unchanged, glutathione peroxidase activity was decreased, and catalase activity was elevated in kidney homogenates of Cd-administrated group. However, lycopene treatment reversed Cd-changed enzyme activities to the control level. Xanthine oxidase activity and TNF-alpha concentration were not altered by Cd administration, indicating that superoxide anion production and inflammation were not stimulated. Cadmium did not change NO levels in kidney homogenates but decreased those in plasma, and this effect was not prevented by lycopene supplementation. The result suggests that consumption of adequate levels of lycopene may be useful to prevent heavy-metal-induced LPO and body weight loss.
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PMID:Oral administration of lycopene reverses cadmium-suppressed body weight loss and lipid peroxidation in rats. 1787 60

Erdosteine is a mucolytic agent having antioxidant properties through its active metabolites in acute injuries induced by pharmacological drugs. This study was designed to investigate the renoprotective potential of Erdosteine against gentamicin (GM)-induced renal dysfunction by using Technetium-99 m dimercaptosuccinic acid (Tc-99 m DMSA) uptake and scintigraphy in rats. For this purpose, male Wistar rats were randomly allotted into one of the four experimental groups: Control, Erdosteine, GM, and GM + Erdosteine groups. GM and GM + Erdosteine groups received 100 mg/kg GM intramuscularly for 6 days. In addition, Erdosteine and GM + Erdosteine groups received 50 mg/kg Erdosteine orally for 6 days. Renal function tests were assessed by serum blood urea nitrogen (BUN), creatinine levels, as well as scintigraphic and tissue radioactivity measurements with Tc-99 m DMSA. Renal oxidative damage was determined by renal malondialdehyde (MDA) levels, by antioxidant enzyme activities; superoxide dismutase (SOD) and catalase (CAT) and activities of oxidant enzymes; xanthine oxidase (XO) and myeloperoxidase (MPO). GM administration resulted in marked renal lipid peroxidation, increased XO and MPO activities and decreased antioxidant enzyme activities. GM + Erdosteine group significantly had lower MDA levels, higher SOD and CAT activities and lower XO and MPO activities, when compared to GM. Also GM + Erdosteine had lower levels of serum BUN, creatinine and higher renal tissue Tc-99 m DMSA uptake and radioactivity with respect to GM. In conclusion, our results supported a protective role of Erdosteine in nephrotoxicity associated with GM treatment.
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PMID:Renoprotective effect of erdosteine in rats against gentamicin nephrotoxicity: a comparison of 99mTc-DMSA uptake with biochemical studies. 1789 18

In this study, we aimed to investigate the possible protective effects of caffeic acid phenethyl ester (CAPE) on lipid peroxidation (LPO) and the activities of antioxidant enzymes in the liver of rats exposed to the 900 MHz electromagnetic field (EMF). EMF of cellular phones may affect biological systems by increasing free radical, which appear mainly to enhance LPO, and by changing the antioxidative activities of liver, thus leading to oxidative damage. CAPE, an active component of propolis extract, exhibits antioxidant properties and several studies suggest that supplementation with antioxidant can influence EMF exposure induced hepatotoxicity. Thirty male Sprague-Dawley rats were divided into three groups: control (n = 10), 900 MHz EMF (n = 10) and 900 MHz EMF + CAPE (n = 10). CAPE was injected intraperitoneally for 30 days before exposure to EMF. Liver tissue was removed to study the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), xanthine oxidase (XO) and the levels of LPO. The activities of XO, CAT and level of LPO increased in the 900 MHz electromagnetic field (EMF) group compared with the control group, although XO, CAT activities and LPO levels were decreased by 900 MHz EMF + CAPE administration. The activities of SOD and GSH-Px decreased in the 900 MHz EMF group compared with the control group, although their levels were increased by EMF + CAPE administration. It can be concluded that CAPE may prevent the 900 MHz EMF-induced oxidative changes in liver by strengthening the antioxidant defense system by reducing reactive oxygen species and increasing antioxidant enzyme activities.
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PMID:The protective effect of caffeic acid phenethyl ester (CAPE) on oxidative stress in rat liver exposed to the 900 MHz electromagnetic field. 1967 36

Xanthine oxidase (XO) is a key enzyme that can catalyze the conversion of xanthine to uric acid, causing various diseases in humans. We have developed a high-throughput chip-based assay that uses a photodiode array (PDA) microchip system to explore the inhibitory effects of drug analogs on XO. Inhibitory activities of cyclosporin A, aminoglutethimide, dithranol and naringenin against XO were assessed using this chip-based xanthine assay in the presence or absence of the antioxidant enzyme, superoxide dismutase (SOD). In addition, the mechanism of drug action was also disclosed by monitoring the combined effect of respective drug analogs and SOD on XO in the assay. The assessment was based on the red light absorption property of nitroblue tetrazolium (NBT) formazan, formed by free radical-mediated NBT reduction. Compared to naringenin (50 and 100 microM; a known XO inhibitor), cyclosporin A (5 and 10 microM) exhibited similar XO inhibitory activity, whereas dithranol (1 and 3 microM) and aminoglutethimide (2.5 and 5mM) showed minimum XO inhibition. Low standard deviation obtained during the assay demonstrates the preciseness and accuracy of the developed approach. Compared to the existing methods, the developed approach is advantageous due to its simplicity and compatibility with high-throughput screening procedures. Furthermore, this approach can be applied to the early phase of drug discovery screening to explore various drug analogs for their XO inhibitory activities.
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PMID:On-chip assay for determining the inhibitory effects and modes of action of drugs against xanthine oxidase. 1967 20

Familial hypercholesterolemia (FH) is a clinical condition with high risk for developing atherosclerosis. Increased oxidative stress (OS) and FH have been related to atherosclerosis, but no data are available on levels of OS and antioxidant enzyme activity in circulating mononuclear cells (CMCs) from FH patients. Circulating mononuclear cells are important mediators in atherosclerosis development, and chronically increased blood OS present in FH can induce modification in CMC activity. The objective of the study was to analyze the OS levels in CMCs from FH patients and controls. We have selected 30 nonrelated FH index patients and 30 normoglycemic and normocholesterolemic controls matched by age, sex, body mass index, abdominal circumference, and homeostasis model assessment index. Production of free radicals was analyzed by measurement of xanthine oxidase activity in plasma, reduced and oxidized glutathione (GSH and GSSG, respectively), and malonyldialdehyde in levels CMCs. Antioxidant status was analyzed by measuring antioxidant enzyme activity as superoxide dismutase, catalase, and glutathione peroxidase. We have found that FH patients showed significantly higher xanthine oxidase and malonyldialdehyde enzyme activities, as well as increased GSSG and lower GSH values resulting in a higher GSSG/GSH ratio. These data indicate a higher free radical production in plasma and increased OS levels in CMCs from patients than from controls. No significant differences were found in superoxide dismutase, catalase, and glutathione peroxidase activities between both groups. These data show an important alteration of OS regulation in FH and the absence of antioxidant response in CMCs mediated by some of the major antioxidant enzymes.
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PMID:Increased oxidative stress levels and normal antioxidant enzyme activity in circulating mononuclear cells from patients of familial hypercholesterolemia. 1980 85

In this study, antioxidant and free radical scavenging activities of an endemic Salvia species (Salvia brachyantha (Bordz) probed. was assessed in vitro using 1,1-diphenyl-2-picryhydrazyl (DPPH) radical, beta-carotene linoleic acid, superoxide anion radical, hydroxyl radical, and reducing power assays. Regarding our data, the plant extract exhibited antioxidant and radical scavenging activities at different magnitudes of potency. In addition, this study was undertaken to assess whether methanol extract of S. brachyantha could increase the endogenous antioxidant enzymes in cells, and where such increased cellular defences could provide protection against oxidative cell injury. Pre treatment of rat heart cell lines with 100 microg/ml of plant extract for 24h significantly prevented cell damage and enhanced activity of antioxidant enzymes induced by a treatment with xanthine/xanthine oxidase. Increased reactive oxygen species and cell apoptosis induced by xanthine/xanthine oxidase was dose-dependently prevented when cells were pre treated for 24h with plant extract. These results indicated that S. brachyantha could protect against cell injury via induction of the antioxidant enzyme defences. The extract of this plant might be valuable antioxidant natural sources and seemed to be applicable in both healthy medicine and food industry.
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PMID:Antioxidant, free radical scavenging activities of Salvia brachyantha and its protective effect against oxidative cardiac cell injury. 2003 3

Individuals with impaired lipid and glucose metabolism are at increased risk for postprandial oxidative stress. Acute exercise can attenuate the rise in both blood triglyceride (TAG) and glucose, and increase antioxidant enzyme activity after food intake, which may decrease the oxidative stress response. This study investigated the effect of acute exercise on blood TAG and oxidative stress biomarkers in prediabetic women. Sixteen prediabetic women (30 +/- 3 years of age; fasting blood glucose, 107 +/- 3 mg x dL(-1); body mass index, 32 +/- 2 kg x m(-2)) consumed a high-fat meal with and without a session of aerobic exercise 15 minutes preceding the meal (45-minute duration, 65% heart rate reserve), in a random order cross-over design. Blood samples were collected premeal (fasted) and at 1, 2, 4, and 6 hours postmeal and assayed for Trolox equivalent antioxidant capacity (TEAC), xanthine oxidase (XO) activity, hydrogen peroxide (H2O2), malondialdehyde (MDA), TAG, and glucose. No interaction or condition main effects were noted (P > 0.05). However, time main effects were noted for XO, H2O2, MDA, and TAG (P < 0.0001), with values higher from 1 to 6 hours postmeal compared with premeal, and for TEAC (P = 0.05), with values lower at 4 hours postmeal. Glucose remained relatively unchanged (P > 0.05). Acute exercise, performed at the intensity and duration of the present study, does not influence postprandial TAG and oxidative stress in obese prediabetic women. Such individuals may need a greater volume of exercise for measurable effects.
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PMID:Acute exercise does not attenuate postprandial oxidative stress in prediabetic women. 2004 85

Reactive oxygen species (ROS) produce damage to all major cellular constituents. The antioxidant properties of the ethyl acetate fraction of Empetrum nigrum was assessed against hydrogen peroxide (H(2)O(2))-induced cell damage. Empetrum extract was found to scavenge (1) intracellular ROS in cell system, (2) hydroxyl radicals generated by the Fenton reaction (FeSO(4) + H(2)O(2)), and (3) superoxide radicals generated by xanthine/xanthine oxidase in a cell-free system as detected by electron spin resonance (ESR) spectrometry. Cell damage was produced by H(2)O(2) treatment as evidenced by DNA damage, lipid peroxidation, and increased protein carbonyl formation; however, Empetrum extract prevented H(2)O(2)-induced damage to these parameters. Empetrum extract increased viability of Chinese hamster lung fibroblast (V79-4) cells exposed to H(2)O(2), as evidenced by decreased apoptotic nuclear fragmentation, and lower sub G(1) cell population. Further, Empetrum extract restored the cellular antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and heme oxygenase-1 (HO-1), which were reduced by H(2)O(2) treatment. In conclusion, Empetrum extract protected cells against H(2)O(2)-induced cell damage via antioxidant properties by scavenging ROS and enhancing antioxidant enzyme activities.
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PMID:Risk reduction of ethyl acetate fraction of Empetrum nigrum var. japonicum via antioxidant properties against hydrogen peroxide-induced cell damage. 2007 24


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