Serum Xanthine Oxidase Activity Research Articles

Changes in Systemic Blood Pressure and Serum Xanthine Oxidase Activity Induced by The Stimulation of Alcohol Metabolism by Fructose in Man

Changes in Systemic Blood Pressure and Serum Xanthine Oxidase Activity Induced by The Stimulation of Alcohol Metabolism by Fructose in Man

Effects of Genistein, Apigenin, Quercetin, Rutin and Astilbin on serum uric acid levels and xanthine oxidase activities in normal and hyperuricemic mice

Flavonoids are widely found in plants and many of them possess biological and pharmacological activities. In the present study, we assessed the effects of the flavonoids Genistein, Apigenin, Quercetin, Rutin and Astilbin on xanthine oxidase (XO) activities in vitro, and in serum and the liver. The effects of the flavonoids on serum uric acid levels were also measured in vivo. In vitro studies indicated that the flavonoids tested did not significantly affect XO activity. However, significant increases and decreases in XO activities were observed in vivo. Moreover, serum XO activity was correlated with serum uric acid levels, while no correlation was observed for liver XO activity. The present study showed that serum uric acid levels in mice treated with the flavonoids tested here are higher than control levels. Therefore, the flavonoids tested here are not candidates for replacing Allopurinol as a treatment to reduce serum uric acid levels.

The significance of serum xanthine oxidase and oxidation markers in acute paraquat poisoning in humans

Objectives Determine xanthine oxidase (XO) activity and oxidative-stress parameters in human acute paraquat poisoning. Design and methods Twnty-five patients and 26 healthy control participants were recruited. Serum XO, superoxide dismutase (SOD), Glutathione (GSH) and malondialdehyde (MDA) were determined by spectrophotometric methods. Results XO activity and MDA levels were higher and SOD activity and GSH level were lower in the patients group. XO activity and MDA level were significantly higher, and the GSH level and SOD activity were lower in the paraquat poisoning fatality group. There was a significant negative correlation between the XO activity and both the SOD and GSH, while there was a significant positive correlation between XO activity and the MDA level in the patients group. Conclusions XO activity contributes to the development of oxidative injury in patients with paraquat poisoning. Serum XO activity could be used as a marker for prognosis in human acute paraquat intoxication.

Dialysis modality-dependent changes in serum metabolites: accumulation of inosine and hypoxanthine in patients on haemodialysis

The body metabolism of patients with end-stage renal disease may be altered in response to long-term dialysis treatment. Moreover, the pattern of serum metabolites could change depending on the type of dialysis modality used. However, dialysis modality-dependent changes in serum metabolites are poorly understood. Our aim was to profile comprehensively serum metabolites by exploiting a novel method of (1)H-NMR-based metabonomics and identify the differences in metabolite patterns in subjects receiving haemodialysis (HD) and peritoneal dialysis (PD). Anuric and non-diabetic HD patients were matched to PD patients for age, sex and dialysis duration. Accurate concentrations of serum metabolites were determined using the target-profiling procedure, and differences in the levels of metabolites were compared using multivariate analysis. Principal Components Analysis score plots showed that the metabolic patterns could be discriminated by dialysis modalities. Hypoxanthine and inosine were present only with HD, whereas serum xanthine oxidase activity and uric acid levels were not different. In contrast, PD was associated with higher levels of lactate, glucose, maltose, pyruvate, succinate, alanine, and glutamate linked to glucose metabolism and the tri-carboxylic acid cycle. Maltose appeared only in patients using icodextrin solution for PD. Known uraemic retention solutes such as urea, creatinine, myo-inositol and trimethylamine-N-oxide were increased in both dialysis groups. Metabonomics shows apparent differences in the profiles of serum metabolites between HD and PD, which were influenced by dialysis-related processes. Inosine and hypoxanthine are present only in HD patients, which is likely to represent more hypoxic and oxidative stress.

The Significance of the Measurement of Serum Xanthine Oxidase and Oxidation Markers in Patients with Acute Organophosphorus Pesticide Poisoning

This study investigated whether xanthine oxidase (XO) plays an important role in the mechanism of toxicity of acute organophosphorus pesticide poisoning (AOPP). The serum activities of XO, superoxide dismutase (SOD), paraoxonase-1 (PON1), butyrylcholinesterase (BChE) and malondialdehyde (MDA) were compared in 49 patients with AOPP and 50 age- and gender-matched healthy controls. Serum XO and MDA activities were higher and the serum SOD, PON1 and BChE activities were lower in the AOPP patients compared with the controls. Pearson correlation analysis demonstrated a significant negative correlation between XO activity and the SOD, PON1 and BChE activities, but a significant positive correlation between XO activity and MDA. These results suggest that increased activity of XO and decreased antioxidant enzyme activity contribute to the development of oxidative injury in AOPP patients. Thus, effective antioxidant therapy may be a therapeutic option following AOPP.

Determination of Serum Adenosine Deaminase and Xanthine Oxidase Levels in Patients with Crimean–Congo Hemorrhagic Fever

OBJECTIVE:Crimean–Congo hemorrhagic fever is an acute viral hemorrhagic fever with a high mortality rate. Despite increasing knowledge about hemorrhagic fever viruses, little is known about the pathogenesis of Crimean–Congo hemorrhagic fever. In this study, we measured serum adenosine deaminase and xanthine oxidase levels in Crimean–Congo hemorrhagic fever patients.METHODS:Serum adenosine deaminase levels were measured with a sensitive colorimetric method described by Giusti and xanthine oxidase levels by the method of Worthington in 30 consecutive hospitalized patients (mean age 42.6 ± 21.0). Laboratory tests confirmed their diagnoses of Crimean–Congo hemorrhagic fever. Thirty-five subjects (mean age 42.9 ± 19.1) served as the control group.RESULTS:There was a significant difference in adenosine deaminase and xanthine oxidase levels between cases and controls (p<0.05). However, neither adenosine deaminase nor xanthine oxidase levels varied with the severity of disease in the cases assessed (p>0.05).CONCLUSION:Adenosine deaminase and xanthine oxidase levels were increased in patients with Crimean–Congo hemorrhagic fever. Elevated serum xanthine oxidase activity in patients with Crimean–Congo hemorrhagic fever may be associated with reactive oxygen species generated by the xanthine/xanthine oxidase system during inflammatory responses. In addition, elevated lipid peroxidation may contribute to cell damage and hemorrhage. The association of cell damage and hemorrhage with xanthine oxidase activity should be further investigated in large-scale studies.

Elevated serum xanthine oxidase activities in patients with Henoch–Schonlein purpura

Elevated serum xanthine oxidase activities in patients with Henoch–Schonlein purpura

The Activities of Paraoxonase, Xanthine Oxidase, Adenosine Deaminase and the Level of Nitrite in Pseudoexfoliation Syndrome

Aim: Our purpose was to investigate the possible roles of nitrite levels and the activity of paraoxonase (PON), xanthine oxidase (XO) and adenosine deaminase (ADA) in the pathogenesis of pseudoexfoliation (PEX) syndrome. Methods: Serum samples were taken from 43 patients with PEX and 41 control subjects. The serum PON, XO and ADA activities and nitrite levels were assayed by spectrophotometric methods. Results: The PON, ADA and XO activities and nitrite levels (means ± standard deviation) were 81.72 ± 42.56 U/ml, 19.75 ± 5.72 U/l, 0.16 ± 0.09 U/l and 94.23 ± 27.72 μmol/l in the PEX group, respectively. In the control group, the PON, ADA and XO activities and the nitrite levels were 111.02 ± 43.51 U/ml, 15.21 ± 3.93 U/l, 0.13 ± 0.06 U/l and 61.96 ± 19.05 μmol/l, respectively. The serum PON activity was significantly lower in the PEX group when compared with the control group. The serum XO and ADA activities and nitrite levels were significantly higher in the patients with PEX when compared with the control subjects. Conclusion: Decreased PON (an antioxidant enzyme) activity as well as increased ADA and XO activities and nitrite levels indicate that oxidative stress is increased and purine metabolism is altered in PEX syndrome.

Xanthine oxidase inhibitor allopurinol attenuates the development of diabetic cardiomyopathy

In this study, we investigated the effect of the xanthine oxidase (XO) inhibitor, allopurinol (ALP), on cardiac dysfunction, oxidative-nitrosative stress, apoptosis, poly(ADP-ribose) polymerase (PARP) activity and fibrosis associated with diabetic cardiomyopathy in mice. Diabetes was induced in C57/BL6 mice by injection of streptozotocin. Control and diabetic animals were treated with ALP or placebo. Left ventricular systolic and diastolic functions were measured by pressure-volume system 10 weeks after established diabetes. Myocardial XO, p22(phox), p40(phox), p47(phox), gp91(phox), iNOS, eNOS mRNA and/or protein levels, ROS and nitrotyrosine (NT) formation, caspase3/7 and PARP activity, chromatin fragmentation and various markers of fibrosis (collagen-1, TGF-beta, CTGF, fibronectin) were measured using molecular biology and biochemistry methods or immunohistochemistry. Diabetes was characterized by increased myocardial, liver and serum XO activity (but not expression), increased myocardial ROS generation, p22(phox), p40(phox), p47(phox), p91(phox) mRNA expression, iNOS (but not eNOS) expression, NT generation, caspase 3/7 and PARP activity/expression, chromatin fragmentation and fibrosis (enhanced accumulation of collagen, TGF-beta, CTGF and fibronectin), and declined systolic and diastolic myocardial performance. ALP attenuated the diabetes-induced increased myocardial, liver and serum XO activity, myocardial ROS, NT generation, iNOS expression, apoptosis, PARP activity and fibrosis, which were accompanied by improved systolic (measured by the evaluation of both load-dependent and independent indices of myocardial contractility) and diastolic performance of the hearts of treated diabetic animals. Thus, XO inhibition with ALP improves type 1 diabetes-induced cardiac dysfunction by decreasing oxidative/nitrosative stress and fibrosis, which may have important clinical implications for the treatment and prevention of diabetic cardiomyopathy and vascular dysfunction.

Contribution of xanthine oxidase-derived superoxide to chronic hypoxic pulmonary hypertension in neonatal rats

Xanthine oxidase (XO)-derived reactive oxygen species (ROS) formation contributes to experimental chronic hypoxic pulmonary hypertension in adults, but its role in neonatal pulmonary hypertension has received little attention. In rats chronically exposed to hypoxia (13% O(2)) for 14 days from birth, we examined the effects of ROS scavengers (U74389G 10 mg.kg(-1).day(-1) or Tempol 100 mg.kg(-1).day(-1) ip) or a XO inhibitor, Allopurinol (50 mg.kg(-1).day(-1) ip). Both ROS scavengers limited oxidative stress in the lung and attenuated hypoxia-induced vascular remodeling, confirming a critical role for ROS in this model. However, both interventions also significantly inhibited somatic growth and normal cellular proliferation in distal air spaces. Hypoxia-exposed pups had evidence of increased serum and lung XO activity, increased vascular XO-derived superoxide production, and vascular nitrotyrosine formation. These changes were all prevented by treatment with Allopurinol, which also attenuated hypoxia-induced vascular remodeling and partially reversed inhibited endothelium-dependent arterial relaxation, without affecting normal growth and proliferation. Collectively, our findings suggest that XO-derived superoxide induces endothelial dysfunction, thus impairing pulmonary arterial relaxation, and contributes to vascular remodeling in hypoxia-exposed neonatal rats. Due to the potential for adverse effects on normal growth, targeting XO may represent a superior "antioxidant" strategy to ROS scavengers for neonates with pulmonary hypertension.

Protection against Oxidative Stress in Diabetic Rats by Wheat Bran Feruloyl Oligosaccharides

Diabetes is one of the most costly of the chronic diseases and is increasing in epidemic proportions in developing countries. It has been found that some antioxidants play a role in protection against oxidative stress, which is associated with diabetes. In this study, enzyme-released feruloyl oligosaccharides from wheat bran were given intragastrically (ig) to test their effect on antioxidant capacity, body weight restoring capacity, and serum glucose level in alloxan-induced diabetic Sprague-Dawley (SD) rats, using sodium ferulate and vitamin C as positive control groups. The levels of blood glucose, total antioxidant capacity (TAOC), and malondiadehyde (MDA) and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and xanthine oxidase (XOD) were determined in rat serum, liver, and testes. Feruloyl oligosaccharides significantly increased TAOC level, GSH-Px, and SOD activities, but decreased blood glucose and MDA levels and XOD activity in serum, liver, and testes of diabetic rats compared to diabetic controls. Feruloyl oligosaccharides were, overall, more efficient in mitigating oxidative damage in diabetic rats than sodium ferulate and vitamin C. In this feruloyl oligosaccharide feeding study, the antioxidant restoring capacity varied across the tissues observed, and also the activity change of the various antioxidant enzymes varied within a single tissue. Feruloyl oligosaccharides showed greater antioxidant capacity in vivo than in vitro when compared with vitamin C.

Oxidative stress and antioxidant defenses in serum of patients with non-alcoholic steatohepatitis

Objectives: Oxidative stress is an important pathophysiological mechanism in non-alcoholic steatohepatitis (NASH). We aimed to evaluate serum xanthine oxidase (XO) (as a generator of reactive oxygen species), superoxide dismutase (SOD), glutathione peroxidase (GSH Px), paraoxonase (PON1) activities, nitric oxide (NO) and thiol levels in patients with NASH. Design and methods: A total of 35 patients with NASH and 31 age-and-gender-matched healthy subjects were enrolled in the study as control group. Serum levels of XO, NO, SOD, GSH Px, PON1 and thiol were determined by spectrophotometric methods. Results: Serum XO activities were higher in the patients with NASH than the controls ( p < 0.001). Serum NO levels, SOD, GSH Px, PON1 activities and thiol levels were lower in the patients with NASH than the controls ( p < 0.031, p < 0.019, p < 0.001, p < 0.001, p < 0.001, respectively). Conclusions: Increased oxidative stress in patients with NASH may result in a pro-oxidation environment, which in turn could result in decreased antioxidant enzyme activities and NO levels. Therefore effective antioxidant therapy to inhibit oxidative stress is necessary and agents to increase antioxidant enzyme may be a therapeutic option in NASH.

Serum Xanthine Oxidase activity in normotensive and hypertensive Nigerian pregnant women

Serum Xanthine Oxidase activity in normotensive and hypertensive Nigerian pregnant women

Protective effect of coadministered superoxide dismutase and catalase against stress-induced gastric mucosal lesions.

1. There are conflicting reports as to the protective effect of coadministered native superoxide dismutase (SOD) and catalase against gastric mucosal lesions in rats with water immersion restraint (WIR) stress. It is unclear how coadministered native SOD and catalase protect against WIR stress-induced gastric mucosal lesions. Therefore, in the present study, we re-examined the protective effect of coadministered native SOD and catalase against gastric mucosal lesions in rats with WIR stress. 2. Gastric mucosal lesions were induced in Wistar rats by 3 h WIR. Rats were injected subcutaneously with a mixture of purified bovine erythrocyte SOD and bovine liver catalase 1 h before the onset of WIR. Ulcer index, serum SOD, catalase and xanthine oxidase (XO), uric acid and gastric mucosal SOD, catalase, XO, myeloperoxidase (MPO; an index of tissue neutrophil infiltration), non-protein sulfhydryl (NP-SH) and thiobarbituric acid-reactive substances (TBARS; an index of lipid peroxidation) were assayed in all rats used. 3. Rats with 3 h WIR showed gastric mucosal lesions. Pre-administration of SOD plus catalase to rats with WIR prevented lesion formation. In the serum of rats with WIR alone, XO activity and uric acid concentration increased, whereas SOD and catalase activities did not change. Pre-administration of SOD plus catalase to rats with WIR did not affect increased serum XO activity and uric acid concentration, but did increase serum SOD and catalase activities. In the gastric mucosa of rats with WIR alone, increases in MPO activity and TBARS concentration and a decrease in NP-SH concentration occurred, whereas XO, SOD and catalase activities did not change. Pre-administration of SOD plus catalase to rats with WIR attenuated the changes in gastric mucosal MPO activity and TBARS and NP-SH concentrations, but did not affect gastric mucosal XO, SOD and catalase activities. Pre-administration of SOD plus catalase (in an inactivated form) to rats with WIR had no effect on gastric mucosal lesion formation and the levels of serum and gastric mucosal parameters studied. 4. These results indicate that coadministered native SOD and catalase protect against gastric mucosal lesions in rats with WIR stress and suggest that this protective effect of coadministered native SOD and catalase could be due to their activity to scavenge XO-derived active oxygen species that are increased in the blood.

Contribution of Xanthine Oxidase-Derived Oxygen Free Radicals to the Development of Carbon Tetrachloride-Induced Acute Liver Injury in Rats

We examined how oxygen free radicals derived from xanthine oxidase (XOD) contribute to the development of carbon tetrachloride (CCl4)-induced acute liver injury in rats. In rats treated with CCl4 (1ml/kg), liver injury appeared 3h after the treatment and developed by 24h, judged from the serum levels of transaminases. Hepatic and serum XOD activities and serum uric acid concentration did not change 6h after CCl4 treatment, but they all increased at 12h and further increased at 24h. An increase in the concentration of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, and decreases in reduced glutathione concentration and Cu, Zn-superoxide dismutase (SOD) activity, but not Mn-SOD activity, were observed in the liver at 6h after CCl4 treatment and these changes were further enhanced at 24h. When allopurinol (50mg/kg), an XOD inhibitor, was administered to CCl4-treated rats 6h after CCl4 treatment, liver injury progression was prevented with attenuation of increased hepatic and serum XOD activities, serum uric acid concentration, and hepatic TBARS concentration and decreased hepatic reduced glutathione concentration and Cu, Zn-SOD activity at 24h after CCl4 treatment. These results indicate that XOD-derived oxygen free radicals contribute to the progression of CCl4-induced acute liver injury in rats both by stimulating hepatic lipid peroxidation and by disrupting hepatic antioxidant defense system.

Hepatotoxicity of ricin, saporin or a saporin immunotoxin: xanthine oxidase activity in rat liver and blood serum

Male Wistar rats each received an i.p injection of the ribosome-inactivating proteins ricin or saporin, or a Ber-H2 (anti-CD30)-saporin immunotoxin at a dose corresponding to three times the LD50 calculated for mice. Animals were killed 24, 48 or 72 h after treatment. Histological examination showed hepatic necrosis in all treated animals, although the sinusoidal lining was affected only in ricin-poisoned rats. The activities of xanthine dehydrogenase (D-form) and oxidase (O-form) were determined spectrophotometrically in liver and serum samples. In ricin-treated animals the liver enzyme was progressively converted from the D- to the O-form, which accounted for more than 60% of total activity after 48 h of poisoning, whilst no change in the xanthine oxidase activity was found in the serum. In the liver of rats treated with free or Ber-H2-conjugated saporin, the D-form was more than 75%, as in normal animals. In the same animals the serum xanthine oxidase activity was up to three-fold control values. The determination of serum xanthine oxidase may prove helpful in the evaluation of liver damage in patients treated with immunotoxins. It may become a diagnostic tool for the differential diagnosis of liver diseases.

Xanthine oxidase contributes to lung leak in rats subjected to skin burn.

We found that rats subjected to thermal skin injury (skin burn) had increased serum xanthine oxidase (XO) activities, increased serum complement activation (decreased serum CH50 levels), increased erythrocyte (RBC) fragility, increased lung neutrophil accumulation, and increased lung leak compared to sham-treated rats. Treatment of rats with allopurinol (an XO inhibitor) not only decreased serum XO activity, but also decreased complement activation, RBC fragility, lung neutrophil accumulation, and lung leak abnormalities in rats subjected to skin burn. We conclude that XO may contribute to acute lung injury and a number of events associated with the development of acute lung leak following skin burn.

Effects of allopurinol on endotoxin-induced increase in serum xanthine oxidase in the horse

Using a modified bovine milk enzyme kinetic assay, xanthine oxidase activity of serum collected from 34 adult, healthy horses of both sexes was determined. Enzyme activity varied from 0 to 126 mU litre-1 with a mean of 44.95 +/- 21.05 mU litre-1. The optimal pH and temperature for maximal activity were 7.8 and 28 degrees C, respectively. Freezing the serum for four days at -70 degrees C did not destroy the enzyme activity. Various doses (25, 50 and 75 micrograms kg-1, intraperitoneally) of endotoxin (lipopolysaccharide D1 Escherichia coli O26:B6) previously known to have caused moderate to severe systemic clinical signs of endotoxaemia in horses produced a significant dose related increase in serum xanthine oxidase activity. Pretreatment (12 hours) with allopurinol (5 and 50 mg kg-1, intravenously [corrected]) significantly reduced the rise in xanthine oxidase activity in endotoxin (50 micrograms kg-1, intraperitoneally) treated horses. The results of this study suggest that xanthine oxidase catalysed production of superoxide radicals may play a role in the pathogenesis of endotoxaemia and that allopurinol, an alternate substrate, should be further evaluated for its therapeutic potential in endotoxin related systemic diseases in horses.

Spectrophotometric assay of xanthine oxidase with 2,2'-azino-di(3-ethylbenzthiazoline-6-sulphonate) (ABTS) as chromogen

A new method for the determination of xanthine oxidase activity, based on the oxidation of 2, 2'-azino-di(3-ethylbenzthiazoline-6-sulphonate) (ABTS) by use of uricase and peroxidase, is described. The absorbance increase of the oxidized form of ABTS, measured after 10 min at 410 nm is proportional to xanthine oxidase activity. The method is sensitive, precise (CV below 8.3%), and linear up to 20 U/l. The analytical recovery of the ABTS-method was quantitative. Comparison with the UV and colorimetric NBT-method gave good correlation ( r ⩾ 0.984). Reference values for serum xanthine oxidase activities determined with the new ABTS-method on 83 healthy persons are 0 to 1.20 U/l.

Human serum xanthine oxidase: Fluorometric assay applicable to the investigation of liver disorders

1. 1. A fluorometric assay for serum xanthine oxidase activity that could be used as a back-up to current tests in the differential diagnosis of acute liver damage is described. 2. 2. High levels of serum xanthine oxidase activity were found in acute liver damage. Values were low in other liver or non-liver diseases.