G Zhao, IS Ayene and AB Fisher
Institute for Environmental Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6068, USA.

We have previously shown that isolated, oxygen-ventilated rat lungs generate reactive oxygen species during ischemia and reperfusion. To evaluate the role of free iron in lung ischemia/reperfusion injury, we measured desferrioxamine-chelatable iron (DC-Fe), protein carbonyls, and thiobarbituric acid reactive substances (TBARS) in lungs subjected to global ischemia and reperfusion. There were no changes in DC-Fe, TBARS, or protein carbonyls during 2 h of control perfusion. There was a 2.3-fold increase in DC-Fe during 1 h ischemia and a further doubling during reperfusion. Results were similar when lungs were ventilated with O2 or N2. Lung TBARS increased 214% during ischemia/reperfusion with oxygen ventilation; unlike DC-Fe release, this change was blocked by N2 ventilation. Protein carbonyl content of the lung also increased significantly (113%) with ischemia/reperfusion. Ferric 8- hydroxyquinoline added to the perfusate before ischemia increased DC-Fe in lung tissue and significantly enhanced the lipid and protein oxidation of ischemic/reperfused lungs. The added perfusate iron had no effect on control lungs. Proteins isolated from the iron-supplemented ischemic/reperfused lungs were resistant to further in vitro oxidation induced by hydrogen peroxide (30 microM) whereas proteins from control perfused lungs were oxidized under these conditions. These results indicate that DC-Fe plays an important role in lung oxidative injury with ischemia/reperfusion. DC-Fe is released from iron-storage sites during ischemia and promotes tissue oxidation when oxygenation is maintained during ischemia or restored during reperfusion.

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