The pathophysiology of superoxide: roles in inflammation and ischemia

1982 ◽  
Vol 60 (11) ◽  
pp. 1346-1352 ◽  
Author(s):  
Joe M. McCord ◽  
Ranjan S. Roy
Keyword(s):  
Superoxide Dismutase ◽  
Xanthine Oxidase ◽  
Superoxide Radical ◽  
Tissue Injury ◽  
Xanthine Dehydrogenase ◽  
Chemotactic Factor ◽  
Calcium Transients ◽  
Acute Inflammatory Response ◽  
Superoxide Generation ◽  
Inflammatory Action

The superoxide radical plays major roles in the neutrophil-mediated acute inflammatory response and in postischemic tissue injury, although the sources and actions of the radical are quite different in these two pathological states. While neutrophils produce superoxide for the primary purpose of aiding in the killing of ingested microbes, a second useful function has evolved. The superoxide released from actively phagocytosing neutrophils serves to attract more neutrophils by reacting with, and activating, a latent chemotactic factor present in plasma. Superoxide dismutase, by preventing the activation of this superoxide-dependent chemotactic factor, exerts potent anti-inflammatory action. During ischemia, energy-starved tissues catabolize ATP to hypoxanthine. Calcium transients in these cells appear to activate a calmodulin regulated protease which attacks the enzyme xanthine dehydrogenase, converting it to a xanthine oxidase capable of superoxide generation. When the tissue is reperfused and reoxygenated, all the necessary components are present (xanthine oxidase, hypoxanthine, and oxygen) to produce a burst of superoxide which results in extensive tissue damage. Ischemic tissues are protected by superoxide dismutase or allupurinol, an inhibitor of xanthine oxidase.

scholarly journals The rate of reaction of superoxide radical ion with oxyhaemoglobin and methaemoglobin

1976 ◽  
Vol 155 (3) ◽  
pp. 503-510 ◽  
Author(s):  
H C Sutton ◽  
P B Roberts ◽  
C C Winterbourn
Keyword(s):  
Superoxide Dismutase ◽  
Xanthine Oxidase ◽  
Rate Constants ◽  
Superoxide Radical ◽  
Radical Ions ◽  
Catalysed Oxidation ◽  
Rate Of Reaction ◽  
Radiolytic Reduction

Superoxide radical ions (O2-) produced by the radiolytic reduction of oxygenated formate solutions and by the xanthine oxidase-catalysed oxidation of xanthine were shown to oxidize the haem groups in oxyhaemoglobin and reduce those in methaemoglobin as in reactions (1) and (2): (see articles) Reaction (1) is suppressed by reaction (8) when [O2-]exceeds 10 muM, but consumes all the O2- generated in oxyhaemoglobin solutions when [oxyhaemoglobin] greater than 160 muM and [O2-]less than 1 nM at pH 7. The yield of reaction (2) is also maximal in methaemoglobin solutions under similar conditions, but less than one haem group is reduced per O2- radical. From studies of (a) the yield of reactions (1) and (2) at variable [haemoglobin] and rates of production of O2-, (b) their suppression by superoxide dismutase, and (c) equilibria observed with mixtures of oxyhaemoglobin and methaemoglobin, it is shown that k1/k2=0.7 +/- 0.2 and k1 = (4 +/- 1) × 10(3) M-1-S-1 At pH7, and k1 and k2 decrease with increasing pH. Concentrations and rate constants are expressed in terms of haem-group concentrations. Concentrations of superoxide dismutase observed in normal erythrocytes are sufficient to suppress reactions (1) and (2), and hence prevent the formation of excessive methaemoglobin.

Effects of ischemia and oxygen radicals on mucosal albumin clearance in intestine

1982 ◽  
Vol 242 (5) ◽  
pp. G448-G454 ◽  
Author(s):  
B. Grogaard ◽  
D. A. Parks ◽  
D. N. Granger ◽  
J. M. McCord ◽  
J. O. Forsberg
Keyword(s):  
Superoxide Dismutase ◽  
Xanthine Oxidase ◽  
Superoxide Radical ◽  
Arterial Occlusion ◽  
Oxidase Inhibitor ◽  
Radical Scavenger ◽  
Perfusion Rate ◽  
Xanthine Oxidase Inhibitor ◽  
Luminal Perfusion ◽  
Albumin Clearance

Mucosal albumin clearance was measured in jejunal segments of dogs under control conditions, after arterial occlusions of varying duration (15 min-4 h), and during intraluminal perfusion with hypoxanthine-xanthine oxidase. Albumin clearance rates were estimated from the luminal perfusion rate and the activity of protein-bound 125I in the perfusate and plasma. Arterial occlusion of 30-min to 4-h duration produced a significant increase in mucosal albumin clearance. The magnitude of the rise in albumin clearance was directly related to the duration of arterial occlusion. Pretreatment with superoxide dismutase, a superoxide radical scavenger, or allopurinol, a xanthine oxidase inhibitor, did not prevent the increased albumin clearance induced by 1 h of occlusion. Intraluminal perfusion with hypoxanthine-xanthine oxidase significantly increased mucosal albumin clearances. This increase was prevented by superoxide dismutase. The results of this study indicate that arterial occlusions and enzymatically generated superoxide radicals increase mucosal albumin clearance.

scholarly journals Free-radical chain oxidation of 2-nitropropane initiated and propagated by superoxide

1986 ◽  
Vol 237 (2) ◽  
pp. 505-510 ◽  
Author(s):  
C F Kuo ◽  
I Fridovich
Keyword(s):  
Superoxide Dismutase ◽  
Free Radical ◽  
Crown Ether ◽  
Co Oxidation ◽  
Xanthine Oxidase ◽  
Superoxide Radical ◽  
Radical Chain ◽  
Chain Oxidation ◽  
Radical Chain Oxidation ◽  
Oxidase Reaction

The superoxide radical O2.-, whether produced by the xanthine/xanthine oxidase reaction or infused as KO2, solubilized by a crown ether in dry dimethyl sulphoxide, initiated a free-radical chain oxidation of anionic 2-nitropropane. Superoxide dismutase, but not catalase, inhibited oxidation of the nitroalkane. Xanthine oxidase suffered a syncatalytic inactivation, during the co-oxidation of 2-nitropropane, which was reversed by dialysis. Cyanide exacerbated this syncatalytic inactivation and rendered it irreversible. The frequently observed oxidations of nitroalkanes by flavoenzymes now need to be re-examined to clarify the extent to which O2.--initiated free-radical chain oxidation contributed to the overall nitroalkane oxidation.

Influence of exogenously generated oxidant species on myocardial function

1986 ◽  
Vol 250 (4) ◽  
pp. H595-H599 ◽  
Author(s):  
A. S. Blaustein ◽  
L. Schine ◽  
W. W. Brooks ◽  
B. L. Fanburg ◽  
O. H. Bing
Keyword(s):  
Superoxide Dismutase ◽  
Xanthine Oxidase ◽  
Myocardial Function ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Base Line ◽  
Active Tension ◽  
Tension Development ◽  
Disease States ◽  
Scavenging Enzymes

Oxygen-derived free radicals (OFR) have been implicated as mediators of tissue injury in various disease states. Their participation in myocardial injury due to ischemia-reperfusion has also been suggested. To characterize the mechanical dysfunction associated with OFR-induced injury, we studied alterations in isometric contractions of rat papillary muscle at 28 degrees C. A purine-xanthine oxidase system was used to generate OFR. Neither purine nor xanthine oxidase alone had significant effects on rest or active tension, duration of the contraction, or peak rates of tension development or decline. In contrast, their combination resulted in a reduction of active tension to 38% of base-line values without alteration in rest tension. This reduction was largely due to a decline in the peak rate of tension development. When catalase or superoxide dismutase was introduced into the bath prior to the generation of OFR, catalase but not superoxide dismutase offered essentially complete functional protection. These results substantiate that impaired myocardial function can result from exposure to OFR. In this case the active radicals appear to be either peroxides or hydroxyl and not superoxide. These observations provide a basis for understanding the functional protection afforded ischemic myocardium by OFR scavenging enzymes.

Calcium and free radicals in hypoxia/reoxygenation injury of renal epithelial cells

1994 ◽  
Vol 266 (1) ◽  
pp. F13-F20 ◽  
Author(s):  
E. L. Greene ◽  
M. S. Paller
Keyword(s):  
Free Radicals ◽  
Xanthine Oxidase ◽  
Renal Cell ◽  
Superoxide Radical ◽  
Cell Injury ◽  
Oxygen Free Radicals ◽  
Xanthine Dehydrogenase ◽  
Oxygen Free Radical ◽  
Lactate Dehydrogenase Release ◽  
Radical Production

Hypoxia and reoxygenation (H/R) generate oxygen free radicals that result in renal cell injury. We tested the roles of calcium and calmodulin in mediating xanthine oxidase-derived oxygen free radical production during H/R. Lowering extracellular Ca2+ attenuated lethal cell injury. H/R increased superoxide radical production over basal levels, whereas removing extracellular Ca2+ before hypoxia decreased superoxide radical production to basal levels. Pretreatment with either 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride or thapsigargin, to inhibit release or deplete stores of intracellular Ca2+, did not affect injury following H/R. Ionomycin increased lactate dehydrogenase release during H/R but did not increase superoxide radical to levels greater than that observed for H/R alone. The calmodulin inhibitors trifluoperazine, calmidazolium, or N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide decreased cell injury to varying degrees. Trifluoperazine also decreased superoxide radical production during H/R and was shown to inhibit the conversion of xanthine dehydrogenase to xanthine oxidase. Cell injury and superoxide radical production correlated with cytosolic free Ca2+ during H/R as determined with the Ca(2+)-sensitive fluoroprobe indo 1. Cytosolic free Ca2+ increased slightly during hypoxia and showed a dramatic increase as soon as cells were reoxygenated. Cells incubated in a Ca(2+)-free medium actually showed a small decrease in intracellular Ca2++ despite H/R. In summary, Ca2+ derived from extracellular sources promoted superoxide radical production and renal cell injury by a calmodulin-dependent conversion of xanthine dehydrogenase to xanthine oxidase, a major source of oxygen free radicals during H/R.

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