scholarly journals Xanthine Oxidase Does Not Contribute to Apoptosis after Brain Hypoxia-Ischemia in Immature Rabbits

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Anthony Moretti ◽  
Alma Ramirez ◽  
Richard Mink
Keyword(s):  
Free Radicals ◽  
Xanthine Oxidase ◽  
Caspase 3 ◽  
Oxygen Free Radicals ◽  
Cerebral Injury ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Brain Hypoxia ◽  
Hypoxia Ischemia

Background. The mechanisms involving the initiation of apoptosis after brain hypoxia-ischemia through caspase activation are not fully defined. Oxygen free radicals may be an important mediator of caspase initiation with reactive oxygen species generated by xanthine oxidase (XO) being one potential source. The purpose of this study was to examine the role of XO in apoptosis after global cerebral injury. Methods. Immature rabbits were subjected to 8 minutes hypoxia and 8 minutes ischemia and then 4 hours of reperfusion. In one group (n=5), the XO substrate xanthine was infused to generate more oxygen free radicals to promote apoptosis while in another (n=5), the XO inhibitor allopurinol was given to reduce apoptosis by preventing free radical production (n=5). Control animals (n=4) received the vehicles. Caspase 3, 8, and 9 enzyme activities were measured in the cerebral cortex, hippocampus, cerebellum, thalamus, and caudate. Results. Administration of xanthine increased (P<0.05) caspase 3 activity but only in the hippocampus, and pretreatment with allopurinol did not reduce it. No differences (P>0.05) were found in any other region nor were there any changes in caspases 8 or 9 activities. Conclusion. We conclude that XO is not a major factor in inducing apoptosis after hypoxic-ischemic brain injury.

scholarly journals Minimal role of xanthine oxidase and oxygen free radicals in rat renal tubular reoxygenation injury.

1991 ◽  
Vol 1 (7) ◽  
pp. 959-969
Author(s):  
R B Doctor ◽  
L J Mandel
Keyword(s):  
Free Radicals ◽  
Lactate Dehydrogenase ◽  
Xanthine Oxidase ◽  
Oxygen Radicals ◽  
Oxygen Free Radicals ◽  
Proximal Tubules ◽  
Lactate Dehydrogenase Release ◽  
Reoxygenation Injury ◽  
Isolated Rat

The role of xanthine oxidase and oxygen free radicals in postischemic reperfusion injury in the rat kidney remains controversial. Proximal tubules, the focal segment affected by ischemic renal injury, were isolated in bulk, assayed for xanthine oxidase activity, and subjected to 60 min of anoxia or hypoxia and 60 min of reoxygenation to evaluate the participation of xanthine oxidase and oxygen radicals in proximal tubule reoxygenation injury. The total xanthine oxidase in isolated rat proximal tubules was 1.1 mU/mg of protein, approximately 30% to 40% of the activity found in rat intestine and liver. Lactate dehydrogenase release, an indicator of irreversible cell damage, increased substantially during anoxia (39.8 +/- 2.3 versus 9.8 +/- 1.8% in controls) with an additional 8 to 12% release during reoxygenation. Addition of 0.2 mM allopurinol, a potent xanthine oxidase inhibitor, and dimethylthiourea, a hydroxyl radical scavenger, failed to protect against the reoxygenation lactate dehydrogenase release. Analysis of xanthine oxidase substrate levels after anoxia and flux rates during reoxygenation indicates that hypoxanthine and xanthine concentrations are in a 15-fold excess over the enzyme Km and 0.3 mU/mg of protein of xanthine oxidase activity exists during reoxygenation. Hypoxic tubule suspensions had a minimal lactate dehydrogenase release during hypoxia and failed to demonstrate accelerated injury upon reoxygenation. In conclusion, although xanthine oxidase is present and active during reoxygenation in isolated rat proximal tubules, oxygen radicals did not mediate reoxygenation injury.

Evidence for a pathogenetic role of xanthine oxidase in the "stunned" myocardium

1987 ◽  
Vol 252 (3) ◽  
pp. H566-H577 ◽  
Author(s):  
M. I. Charlat ◽  
P. G. O'Neill ◽  
J. M. Egan ◽  
D. R. Abernethy ◽  
L. H. Michael ◽  
...  
Keyword(s):  
Free Radicals ◽  
Xanthine Oxidase ◽  
Myocardial Stunning ◽  
Oxygen Free Radicals ◽  
Contractile Function ◽  
Myocardial Dysfunction ◽  
Stunned Myocardium ◽  
Base Line ◽  
Collateral Flow

Recent evidence suggests that postischemic myocardial dysfunction (or myocardial “stunning”) may be mediated by oxygen free radicals, but the mechanism for their production remains unknown. To explore the role of xanthine oxidase as a potential source of free radicals, open-chest dogs undergoing a 15-min occlusion of the left anterior descending coronary artery (LAD) followed by 4 h of reperfusion (REP) received intravenously either allopurinol (50 mg/kg 48 h, 20 h, and 30 min before occlusion, 10 mg/kg 1 min before REP, and 6.25 mg X kg-1 X h-1 throughout REP, n = 13) or saline (n = 14). The two groups were similar with respect to occluded bed size (postmortem perfusion) and collateral flow (radioactive microspheres). In controls, the transcardiac difference in plasma uric acid (great cardiac vein - arterial concentration) increased 199 +/- 70% (means +/- SE) during ischemia (P less than 0.02) and remained elevated for 5 min after REP; no increase was observed in treated dogs. Regional myocardial function was assessed by measuring systolic wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under base-line conditions and similar degrees of dyskinesis during ischemia. Following REP, however, recovery of contractile function (expressed as percent of preocclusion values) was considerably greater in allopurinol-treated as compared with control dogs: 57 +/- 14 vs. -22 +/- 16 (P less than 0.01) at 1 h, 70 +/- 13 vs. -15 +/- 15 (P less than 0.001) at 2 h, 65 +/- 14 vs. -28 +/- 13 (P less than 0.001) at 3 h, and 68 +/- 13 vs. -17 +/- 14 (P less than 0.001) at 4 h. These differences could not be ascribed to hemodynamic factors. The results suggest that xanthine oxidase is a source of the oxygen free radicals responsible for myocardial stunning following a brief episode of reversible regional ischemia.

scholarly journals Effects of sevoflurane on rats with ischemic brain injury and the role of the TREK-1 channel

2017 ◽  
Vol 14 (4) ◽  
pp. 2937-2942 ◽  
Author(s):  
Lixiao Pan ◽  
Fengyun Yang ◽  
Caixia Lu ◽  
Changxin Jia ◽  
Qing Wang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Ischemic Brain

Strand scission in DNA induced by dietary flavonoids: role of Cu(I) and oxygen free radicals and biological consequences of scission

1992 ◽  
Vol 111 (1-2) ◽  
Author(s):  
Arshad Rahman ◽  
Fabeha Fazal ◽  
Julie Greensill ◽  
K. Ainley ◽  
J.H. Parish ◽  
...  
Keyword(s):  
Free Radicals ◽  
Oxygen Free Radicals ◽  
Strand Scission ◽  
Dietary Flavonoids

Free radicals in hypoxic rat diaphragm contractility: no role for xanthine oxidase

2001 ◽  
Vol 281 (6) ◽  
pp. L1402-L1412 ◽  
Author(s):  
Leo M. A. Heunks ◽  
Herwin A. Machiels ◽  
Ronney de Abreu ◽  
Xiao Ping Zhu ◽  
Henricus F. M. van der Heijden ◽  
...  
Keyword(s):  
Free Radicals ◽  
Xanthine Oxidase ◽  
Power Output ◽  
Harmful Effect ◽  
Force Generation ◽  
Muscle Performance ◽  
Rat Diaphragm ◽  
Shortening Velocity ◽  
Contraction Pattern

Recent evidence indicates that hypoxia enhances the generation of oxidants. Little is known about the role of free radicals in contractility of the rat diaphragm during hypoxia. We hypothesized that antioxidants improve contractility of the hypoxic rat diaphragm and that xanthine oxidase (XO) is an important source of free radicals in the hypoxic diaphragm. The effects of N-acetylcysteine (NAC; 18 mM), Tiron (10 mM), and the XO inhibitor allopurinol (250 μM) were studied on isometric and isotonic force generation during hypoxia (Po 2 ∼7 kPa). NAC and Tiron decreased maximal force generation, slowed the shortening velocity, and decreased the power output. Fatigue rate was decreased in the presence of either NAC or Tiron. Allopurinol did not alter the contractility or fatigability of the diaphragm. During hyperoxia (Po 2 ∼85 kPa), neither NAC nor allopurinol affected the contractility or fatigability of the diaphragm. Thus free radicals play a significant role in diaphragm contractility during hypoxia. Whether antioxidants exert a beneficial or harmful effect on muscle performance depends on the contraction pattern of the muscle. Free radicals generated by XO do not play a role in diaphragm contractility during either hypoxia or hyperoxia.

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