Role of xanthine oxidase in postischemic microvascular injury in skeletal muscle

1989 ◽  
Vol 257 (6) ◽  
pp. H1782-H1789 ◽  
Author(s):  
J. K. Smith ◽  
D. L. Carden ◽  
R. J. Korthuis
Keyword(s):  
Skeletal Muscle ◽  
Xanthine Oxidase ◽  
Vascular Permeability ◽  
Oxidase Activity ◽  
Ischemia Reperfusion ◽  
Oxidase Inhibitor ◽  
Xanthine Oxidase Inhibitor ◽  
Microvascular Injury ◽  
Xanthine Oxidase Activity

Previous reports indicate that allopurinol, a xanthine oxidase inhibitor, attenuates the microvascular injury produced by reperfusion of ischemic skeletal muscle. To further assess the role of xanthine oxidase in ischemia/reperfusion (I/R) injury, we examined the effect of xanthine oxidase depletion or inhibition on the increase in microvascular permeability produced by I/R. Changes in vascular permeability were assessed by measurement of the solvent drag reflection coefficient for total plasma proteins (sigma) in rat hindquarters subjected to 2 h of ischemia and 30 min of reperfusion in xanthine oxidase-replete and -depleted animals and in animals pretreated with the xanthine oxidase inhibitor oxypurinol. Xanthine oxidase depletion was accomplished by administration of a tungsten-supplemented (0.7 g/kg diet), molybdenum-deficient diet. In animals fed the tungsten diet, muscle total xanthine dehydrogenase plus xanthine oxidase activity was decreased to less than 10% of control values. Estimates of sigma averaged 0.85 +/- 0.04 in nonischemic (continuous perfusion for 2.5 h) hindquarters, whereas muscle xanthine oxidase activity averaged 3.3 +/- 0.4 mU/g wet wt. I/R was associated with a marked decrease in sigma (0.54 +/- 0.02), whereas xanthine oxidase activity was increased to 5.8 +/- 0.5 mU/g wet wt. These results indicate that I/R produced a dramatic increase in vascular permeability coincident with an increase in muscle xanthine oxidase activity. Xanthine oxidase depletion with the tungsten diet or pretreatment with oxypurinol attenuated this permeability increase (sigma = 0.72 +/- 0.03 and 0.77 +/- 0.7, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Activated neutrophils increase microvascular permeability in skeletal muscle: role of xanthine oxidase

1991 ◽  
Vol 70 (5) ◽  
pp. 2003-2009 ◽  
Author(s):  
J. K. Smith ◽  
D. L. Carden ◽  
R. J. Korthuis
Keyword(s):  
Xanthine Oxidase ◽  
Oxidase Activity ◽  
Microvascular Dysfunction ◽  
Oxidase Inhibitor ◽  
Microvascular Permeability ◽  
Deficient Diet ◽  
Xanthine Oxidase Inhibitor ◽  
Xanthine Oxidase Activity ◽  
Activated Neutrophils

To determine the role of xanthine oxidase in the microvascular dysfunction produced by activated granulocytes, we examined the effect of xanthine oxidase depletion or inhibition on the increase in microvascular permeability produced by infusion of the neutrophil activator phorbol myristate acetate (PMA). Changes in vascular permeability were assessed by measurement of the solvent drag reflection coefficient for total plasma proteins (sigma) in rat hindquarters subjected to PMA infusion in xanthine oxidase-replete and -depleted animals, in animals pretreated with the xanthine oxidase inhibitor oxypurinol, and in animals depleted of circulating neutrophils by pretreatment with antineutrophil serum (ANS). Xanthine oxidase depletion was accomplished by administration of a tungsten-supplemented (0.7 g/kg diet) molybdenum-deficient diet. In animals fed the tungsten diet, muscle total xanthine dehydrogenase plus xanthine oxidase activity was decreased to less than 10% of control values. Estimates of sigma averaged 0.84 +/- 0.04 in control hindquarters, whereas PMA infusion was associated with a marked increase in microvascular permeability (decrease in sigma to 0.68 +/- 0.03). PMA infusion also caused an increase in the amount of the radical-producing oxidase form of xanthine oxidase (from 3.9 +/- 0.05 to 5.6 +/- 0.4 mU/g wet wt). ANS pretreatment attenuated this permeability increase (sigma = 0.77 +/- 0.04) and diminished the rise in xanthine oxidase activity (4.9 +/- 0.5 mU/g wet wt). Xanthine oxidase depletion with the tungsten diet or pretreatment with oxypurinol had no effect on this neutrophil-mediated microvascular injury (sigma = 0.69 +/- 0.06 and 0.67 +/- 0.03, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of iron in postischemic microvascular injury

1989 ◽  
Vol 256 (5) ◽  
pp. H1472-H1477 ◽  
Author(s):  
J. K. Smith ◽  
D. L. Carden ◽  
M. B. Grisham ◽  
D. N. Granger ◽  
R. J. Korthuis
Keyword(s):  
Xanthine Oxidase ◽  
Vascular Permeability ◽  
Ischemia Reperfusion ◽  
Iron Chelator ◽  
Solvent Drag ◽  
Microvascular Injury ◽  
Iron Binding Protein ◽  
Oxidant Production ◽  
Permeability Increase

Iron-catalyzed formation of hydroxyl radicals has been postulated to occur during reperfusion of ischemic tissues. To assess the role of iron-catalyzed oxidant production in ischemia/reperfusion (I/R) injury to skeletal muscle, we examined the effects of deferoxamine (an iron chelator) and apotransferrin (an iron-binding protein) on the increased vascular permeability produced by I/R in isolated, pump-perfused rat hindquarters. Solvent drag reflection coefficients (sigma) were measured in hindquarters subjected to 2 h of ischemia and 30 min of reperfusion with either no pretreatment, pretreatment with 50 mg/kg deferoxamine, 200 mg/kg apotransferrin, or iron-loaded deferoxamine (50 mg/kg). I/R alone was associated with an increase in vascular permeability as indicated by the significantly lower estimates of sigma obtained after I/R (0.68 +/- 0.03) compared with those obtained in nonischemic preparations (0.82 +/- 0.02). Pretreatment with deferoxamine or apotransferrin attenuated this permeability increase (sigma = 0.83 +/- 0.03 and 0.86 +/- 0.02, respectively), whereas pretreatment with iron-loaded deferoxamine afforded no protection (sigma = 0.71 +/- 0.02). These findings are consistent with the hypothesis that iron-catalyzed oxidant production is important in the genesis of microvascular injury following I/R. Since the enzyme xanthine oxidase has been implicated as a major source of oxidants generated during reperfusion, we also measured tissue levels of xanthine oxidase and xanthine dehydrogenase in muscle samples obtained from the same hindquarters in which we measured permeability changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Superoxide radicals, immunodeficiency and xanthine oxidase activity: man is not a mouse!

1985 ◽  
Vol 68 (5) ◽  
pp. 561-565 ◽  
Author(s):  
H. A. Simmonds ◽  
A. Goday ◽  
G. S. Morris
Keyword(s):  
Xanthine Oxidase ◽  
Oxidase Activity ◽  
Peritoneal Macrophages ◽  
Oxidase Inhibitor ◽  
Superoxide Radicals ◽  
Human Neutrophils ◽  
Toxic Metabolite ◽  
Xanthine Oxidase Inhibitor ◽  
Human Macrophages ◽  
Xanthine Oxidase Activity

1. The importance of intact adenosine deaminase (ADA) activity in the generation of superoxide anion by xanthine oxidase has been disputed in studies using human neutrophils or mouse macrophages. The latter demonstrated a positive correlation between ADA activity and superoxide production during phagocytosis. The immunodeficiency in inherited ADA deficiency was related to a defect in this process. 2. Since there is considerable interspecies variation in the tissue distribution of xanthine oxidase, the metabolism of [8-14C]deoxyadenosine (dAR), the toxic metabolite which accumulates in inherited ADA deficiency, was investigated in human peritoneal macrophages. 3. Evaluation of the distribution of radiolabel in both cell and medium demonstrated that human macrophages with intact ADA metabolize dAR under physiological conditions to deoxyinosine and hypoxanthine exclusively. The hypoxanthine is further metabolized within the cell to ATP and GTP, via IMP. 4. No xanthine or uric acid could be detected, confirming that in human macrophages xanthine oxidase activity is insignificant, as it is in most other human cells and tissues, except liver and intestinal mucosa. Thus production of superoxide radicals in such cells via this route would be impossible, and consequently unaffected either by ADA deficiency or the xanthine oxidase inhibitor allopurinol.

Effect of acetyl-l-carnitine on lipid peroxidation and xanthine oxidase activity in rat skeletal muscle

1993 ◽  
Vol 18 (11) ◽  
pp. 1157-1162 ◽  
Author(s):  
C. Di Giacomo ◽  
F. Latteri ◽  
C. Fichera ◽  
V. Sorrenti ◽  
A. Campisi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Lipid Peroxidation ◽  
Xanthine Oxidase ◽  
Oxidase Activity ◽  
Rat Skeletal Muscle ◽  
Xanthine Oxidase Activity

scholarly journals Absorption of Hemoglobin Iron: The Role of Xanthine Oxidase in the Intestinal Heme-Splitting Reaction

Blood ◽  
1970 ◽  
Vol 35 (1) ◽  
pp. 94-103 ◽  
Author(s):  
R. BEN DAWSON ◽  
SHEILA RAFAL ◽  
LEWIS R. WEINTRAUB
Keyword(s):  
Epithelial Cell ◽  
Xanthine Oxidase ◽  
Intestinal Epithelial Cell ◽  
Oxidase Inhibitor ◽  
Small Intestinal Mucosa ◽  
Intestinal Epithelial ◽  
Sephadex Column ◽  
Xanthine Oxidase Inhibitor

Abstract Heme from ingested hemoglobin—59Fe is taken into the epithelial cell of the small intestinal mucosa of the dog and the 59Fe subsequently appears in the plasma bound to transferrin. A substance was demonstrated in homogenates of the mucosa which releases iron from a hemoglobin substrate in vitro. Thus: (1) The addition of catalase to the mucosal homogenate reduces the "heme-splitting" reaction. In contrast, sodium azide, a catalase inhibitor, potentiates the reaction. This suggests that a peroxide generating system participates in the "heme-splitting" reaction. (2) Xanthine oxidase, an enzyme present in the intestinal epithelial cell, produces H2O2 by oxidation of its substrate. The addition of allopurinol, a xanthine oxidase inhibitor, to the intestinal mucosal homogenate diminishes the "heme-splitting" reaction. (3) Fractionation of the 50,000 Gm. supernatant of the mucosal homogenate on a G-200 Sephadex column shows the "heme-splitting" activity to have the same elution volume as xanthine oxidase, indicating a similar molecular weight. (4) The addition of a mucosal homogenate to a xanthine substrate results in the production of uric acid. These data suggest that xanthine oxidase in the intestinal epithelial cell is important in the release of iron from absorbed heme. The enzyme mediates the "heme-splitting" reaction by the generation of peroxides which, in turn, oxidize the alpha-methene bridge of the heme ring releasing iron and forming biliverdin.

Ischemia-induced vascular changes: role of xanthine oxidase and hydroxyl radicals

1983 ◽  
Vol 245 (2) ◽  
pp. G285-G289 ◽  
Author(s):  
D. A. Parks ◽  
D. N. Granger
Keyword(s):  
Hydroxyl Radical ◽  
Dimethyl Sulfoxide ◽  
Xanthine Oxidase ◽  
Vascular Permeability ◽  
Hydroxyl Radicals ◽  
Vascular Injury ◽  
Oxygen Radicals ◽  
Intestinal Ischemia ◽  
Xanthine Oxidase Inhibitor

The results of previous studies indicate that oxygen-derived free radicals are responsible for the increased vascular permeability produced by 1 h of intestinal ischemia. The aims of this study were 1) to test the hypothesis that the enzyme xanthine oxidase is the source of oxygen radicals in the ischemic bowel and 2) to assess the role of the hydroxyl radical in the ischemia-induced vascular injury. The capillary osmotic reflection coefficient was estimated from lymphatic protein flux data in the cat ileum for the following conditions: ischemia, ischemia plus pretreatment with allopurinol (a xanthine oxidase inhibitor), and ischemia plus pretreatment with dimethyl sulfoxide (a hydroxyl radical scavenger). The increased vascular permeability produced by ischemia was largely prevented by pretreatment with either allopurinol or dimethyl sulfoxide. These findings support the hypothesis that xanthine oxidase is the source of oxygen radicals produced during ischemia. The results also indicate that hydroxyl radicals, derived from the superoxide anion, are primarily responsible for the vascular injury associated with intestinal ischemia.

A Quantitative Study of Skeletal-Muscle Purines and Pyrazolo[3,4-d]Pyrimidines in Gout Patients Treated with Allopurinol

1971 ◽  
Vol 41 (2) ◽  
pp. 153-158 ◽  
Author(s):  
R. W. E. Watts ◽  
W. Snedden ◽  
R. A. Parker
Keyword(s):  
Skeletal Muscle ◽  
Uric Acid ◽  
Xanthine Oxidase ◽  
Muscle Tissue ◽  
High Resolution Mass Spectrometry ◽  
Oxidase Inhibitor ◽  
Oxidase Deficiency ◽  
Xanthine Oxidase Inhibitor ◽  
Measurable Amount ◽  
Muscle Biopsies

1. Hypoxanthine, xanthine, uric acid, allopurinol and oxipurinol have been determined in skeletal-muscle biopsies by quantitative high-resolution mass spectrometry. 2. The results obtained in six untreated gout patients and in seven gout patients who had been treated with the xanthine oxidase inhibitor allopurinol for periods of about 2 years, have been compared with those obtained on muscle tissue from non-gouty subjects and with the results of previous microscopical studies of the same biopsies. 3. Measurable amounts of xanthine were detected more frequently in the allopurinol-treated gout patients than in the untreated patients. The concentration of uric acid was generally lower in the allopurinol-treated than in the untreated gout patients' muscle; and all except one of the allopurinol-treated subjects' tissue contained a measurable amount of oxipurinol. Allopurinol was detected less frequently than oxipurinol. 4. The concentrations of hypoxanthine and xanthine in the allopurinol-treated patients' muscle tissue are very much less than those which have been reported in congenital xanthine oxidase deficiency. 5. It is concluded that allopurinol can still be recommended as a useful drug in the treatment of gout but that longer studies during the clinical use of the drug would be of value.

scholarly journals Therapeutic Hypothermia Reduces Oxidative Damage and Alters Antioxidant Defenses after Cardiac Arrest

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Fernanda S. Hackenhaar ◽  
Tássia M. Medeiros ◽  
Fernanda M. Heemann ◽  
Camile S. Behling ◽  
Jordana S. Putti ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Oxidative Damage ◽  
Xanthine Oxidase ◽  
Therapeutic Hypothermia ◽  
Oxidase Activity ◽  
Ischemia Reperfusion ◽  
Mild Therapeutic Hypothermia ◽  
Antioxidant Defenses ◽  
Paraoxonase 1 ◽  
Xanthine Oxidase Activity

After cardiac arrest, organ damage consequent to ischemia-reperfusion has been attributed to oxidative stress. Mild therapeutic hypothermia has been applied to reduce this damage, and it may reduce oxidative damage as well. This study aimed to compare oxidative damage and antioxidant defenses in patients treated with controlled normothermia versus mild therapeutic hypothermia during postcardiac arrest syndrome. The sample consisted of 31 patients under controlled normothermia (36°C) and 11 patients treated with 24 h mild therapeutic hypothermia (33°C), victims of in- or out-of-hospital cardiac arrest. Parameters were assessed at 6, 12, 36, and 72 h after cardiac arrest in the central venous blood samples. Hypothermic and normothermic patients had similar S100B levels, a biomarker of brain injury. Xanthine oxidase activity is similar between hypothermic and normothermic patients; however, it decreases posthypothermia treatment. Xanthine oxidase activity is positively correlated with lactate and S100B and inversely correlated with pH, calcium, and sodium levels. Hypothermia reduces malondialdehyde and protein carbonyl levels, markers of oxidative damage. Concomitantly, hypothermia increases the activity of erythrocyte antioxidant enzymes superoxide dismutase, glutathione peroxidase, and glutathione S-transferase while decreasing the activity of serum paraoxonase-1. These findings suggest that mild therapeutic hypothermia reduces oxidative damage and alters antioxidant defenses in postcardiac arrest patients.

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