Ferritin and desferrioxamine attenuate xanthine oxidase-dependent leak in isolated perfused rat lungs.
Iron, through its participation in reactions that generate reactive oxygen species, may contribute to the oxidative lung injury observed in patients with acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). A number of investigators have shown that the endogenous iron storage protein ferritin increases in the blood of patients with and at-risk for ALI and ARDS, but the significance of these increases are not known. In the present investigation, we measured lung tissue levels of thiobarbituric acid reactive substances (TBARS) and lung leak in isolated rat lungs perfused with xanthine oxidase (XO) and purine, an enzymatic system which generates reactive oxygen species. We found that adding ferritin (100 ng/mL) or desferrioxamine (DFO, 10 mM), an iron chelator, to the vascular perfusate solution decreased oxidant-induced leak in isolated rat lungs perfused with XO and purine. Addition of ferritin or DFO also decreased TBARS in isolated rat lungs perfused with XO and purine; neither ferritin nor DFO, however, decreased XO activity in vitro. Our results suggest that oxidative lung leak may be altered by the availability of reactive iron and that ferritin may contribute to protection against oxidative lung injury.
Hybertson
Brooks M
BM
Webb-Waring Institute for Cancer, Aging, and Antioxidant Research, University of Colorado Health Sciences Center, Denver 80262, USA. Brooks.Hybertson@uchsc.edu
Connelly
Kevin G
KG
Buser
Raquel T
RT
Repine
John E
JE
D000818:Animals; D003676:Deferoxamine / Q000494:pharmacology*; D005293:Ferritins / Q000494:pharmacology*; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism*; D010477:Perfusion; D010539:Permeability; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014969:Xanthine Oxidase / Q000494:pharmacology*
D007502:Iron Chelating Agents; D011687:Purines; D017392:Thiobarbituric Acid Reactive Substances; D005293:Ferritins; D007501:Iron; D014969:Xanthine Oxidase; D003676:Deferoxamine; C030985:purine