Anoxia-reoxygenation versus ischemia in isolated rat lungs.
Oxidant generation in anoxia-reoxygenation and ischemia-reperfusion was compared in isolated rat lungs. Anoxia-reoxygenation was produced by N2 ventilation followed by O2 ventilation. After anoxia, lung ATP content was decreased by 59%. Oxygenated ischemia was produced by discontinuing perfusion while ventilation with O2 was maintained. With anoxia-reoxygenation, oxidant generation, evaluated by oxidation of dichlorodihydrofluorescein (H2DCF) to fluorescent dichlorofluorescein, increased 3.6-fold, lung thiobarbituric acid reactive substances (TBARS) increased 342%, conjugated dienes increased 285%, and protein carbonyl content increased 46%. Pretreatment of lungs with 100 microM allopurinol inhibited the reoxygenation-mediated increase in lung fluorescence by 75% and TBARS by 69%. Oxygenated ischemia resulted in an approximately eightfold increase in lung H2DCF oxidation and a fourfold increase in TBARS, but allopurinol had no effect. On the other hand, 100 microM diphenyliodonium (DPI) inhibited the ischemia-mediated increase in lung fluorescence by 69% and lung TBARS by 70%, but it had no effect on the increase with anoxia-reoxygenation. Therefore, both ischemia-reperfusion and anoxia-reoxygenation result in oxidant generation by the lung, but a comparison of results with a xanthine oxidase inhibitor (allopurinol) and a flavoprotein inhibitor (DPI) indicate that the pathways for oxidant generation are distinctly different.
Zhao
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G
Institute for Environmental Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
al-Mehdi
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AB
Fisher
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AB
D000255:Adenosine Triphosphate / Q000378:metabolism; D000332:Aerobiosis; D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D000860:Hypoxia; D066298:In Vitro Techniques; D007511:Ischemia / Q000503:physiopathology*; D015227:Lipid Peroxidation; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D008297:Male; D016877:Oxidants / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D016877:Oxidants; D017392:Thiobarbituric Acid Reactive Substances; D000493:Allopurinol; D000255:Adenosine Triphosphate