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.

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)

Oxygen radicals: effects on intestinal vascular permeability

1984 ◽  
Vol 247 (2) ◽  
pp. G167-G170 ◽  
Author(s):  
D. A. Parks ◽  
A. K. Shah ◽  
D. N. Granger
Keyword(s):  
Free Radicals ◽  
Xanthine Oxidase ◽  
Vascular Permeability ◽  
Oxygen Radicals ◽  
Protein Concentration ◽  
Intestinal Ischemia ◽  
Control Value ◽  
Enzyme Substrate ◽  
Oxygen Derived Free Radicals ◽  
Osmotic Reflection Coefficient

There is now a considerable amount of evidence in the literature implicating oxygen-derived free radicals in the vascular permeability changes associated with intestinal ischemia. To directly assess the effects of oxygen radicals on vascular permeability, hypoxanthine-xanthine oxidase, an enzyme-substrate system known to generate oxygen free radicals, was infused into the arterial supply of autoperfused segments of cat ileum. The osmotic reflection coefficient (sigma d) of intestinal capillaries to total plasma proteins was estimated from the steady-state relationship between lymph-to-plasma total protein concentration ratio and lymph flow. Intra-arterial infusion of hypoxanthine-xanthine oxidase reduced sigma d from a control value of 0.92 to 0.66, indicating an increased vascular permeability. This increase in vascular permeability was significantly attenuated by the addition of superoxide dismutase (sigma d = 0.86), a specific scavenger of superoxide anion (O2-), or dimethylsulfoxide (sigma d = 0.83), the hydroxyl radical (OH X) scavenger, to the infusate. The results of this study indicate that oxygen-derived free radicals, generated by the reaction of hypoxanthine with xanthine oxidase, increase intestinal vascular permeability to an extent comparable with that observed in preparations subjected to 1 h of ischemia.

Role of hydroxyl radical scavengers dimethyl sulfoxide, alcohols and methional in the inhibition of prostaglandin biosynthesis

1976 ◽  
Vol 11 (4) ◽  
pp. 599-607 ◽  
Author(s):  
Rao V. Panganamala ◽  
Hari M. Sharma ◽  
Richard E. Heikkila ◽  
Jack C. Geer ◽  
David G. Cornwell
Keyword(s):  
Hydroxyl Radical ◽  
Dimethyl Sulfoxide ◽  
Radical Scavengers ◽  
Prostaglandin Biosynthesis ◽  
Hydroxyl Radical Scavengers

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.

Effects of free radical generation on mouse pial arterioles: probable role of hydroxyl radicals

1983 ◽  
Vol 245 (1) ◽  
pp. H139-H142 ◽  
Author(s):  
W. I. Rosenblum
Keyword(s):  
Free Radical ◽  
Xanthine Oxidase ◽  
Hydroxyl Radicals ◽  
Free Radical Scavengers ◽  
Radical Scavengers ◽  
Pial Arterioles ◽  
Probable Role ◽  
Radical Generation ◽  
Superoxide Scavenger

Mouse pial arterioles were exposed to the free radical-generating reactants acetaldehyde and xanthine oxidase. Concentrations of 0.5 mM acetaldehyde and 0.1 U/ml xanthine oxidase caused reversible dilations, whereas higher concentrations produced initial constrictions followed by reversible dilations. The following free radical scavengers inhibited the dilation when added to the lower concentrations of reactants: superoxide dismutase, a superoxide scavenger; catalase, an H2O2 scavenger; and mannitol, a hydroxyl scavenger. In addition, pretreatment of the animal with dimethyl sulfoxide, a hydroxyl scavenger, also inhibited the response. The scavengers were also tested against either the dilation produced by increased inspired CO2 or against the dilation produced by local application of 10(-3) M papaverine. No significant effect was observed. The data support the hypothesis that hydroxyl radicals can dilate pial arterioles, since all the scavengers can ultimately reduce levels of hydroxyl generated by acetaldehyde plus xanthine oxidase.

Formation of Hydroxyl Radicals from Hydrogen Peroxide and Iron Salts by Superoxide- and Ascorbate-Dependent Mechanisms: Relevance to the Pathology of Rheumatoid Disease

1983 ◽  
Vol 64 (6) ◽  
pp. 649-653 ◽  
Author(s):  
D. A. Rowley ◽  
B. Halliwell
Keyword(s):  
Hydrogen Peroxide ◽  
Hydroxyl Radical ◽  
Hydroxyl Radicals ◽  
Oxygen Radicals ◽  
Rheumatoid Disease ◽  
Iron Salts ◽  
Low Concentrations ◽  
Short Period ◽  
Generating System

1. Superoxide and hydrogen peroxide are formed by activated phagocytes and react together in the presence of iron salts to form the hydroxyl radical, which attacks hyaluronic acid. Ascorbic acid also interacts with hydrogen peroxide and iron salts to form hydroxyl radical in a reaction independent of superoxide. Since iron salts, ascorbate and activated phagocytes are present in the rheumatoid joint, experiments were designed to see whether ascorbate-dependent or superoxide-dependent formation of hydroxyl radicals would be more important in vivo. 2. in the present study, addition of ascorbate to a superoxide-generating system at concentrations of 100 μmol/l provoked a superoxide-independent formation of hydroxyl radicals for a short period. Lower concentrations of ascorbate did not do this. It is therefore suggested that the superoxide-dependent reaction is probably more important. 3. It is further suggested that destruction of ascorbate by oxygen radicals formed by activated phagocytes accounts for the previously reported low concentrations of this compound in the serum and synovial fluid of rheumatoid patients.

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)

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