Hemoglobin potentiates oxidant injury in isolated rat lungs.
Isolated perfused rat lungs were subjected to oxidant injury induced by tert-butyl hydroperoxide (t-buOOH), which caused a significant increase in capillary permeability as assessed by the change in the capillary filtration coefficient. t-buOOH caused an increase in the change in the capillary filtration coefficient (delta Kfc) of 0.27 +/- 0.05 ml.min.cmH2O-1.100 g lung tissue-1 (mean +/- SE) that was accompanied by an increase in thiobarbituric acid reactive products of lipid peroxidation in the lung perfusate. The addition of hemoglobin to the perfusate potentiated t-buOOH-induced lung injury as evidenced by a significantly greater (P = 0.007) delta Kfc of 0.43 +/- 0.05. t-buOOH also caused hemoglobin to release large quantities of free iron in vitro. The potentiation of t-buOOH-induced lung injury by hemoglobin was prevented by apotransferrin as evidenced by a significant reduction (P = 0.001) in delta Kfc to 0.13 +/- 0.02. No statistically significant (P greater than 0.05) changes in segmental resistances or pulmonary vascular pressures occurred in any of the lungs injured with t-buOOH when compared with time controls. These results demonstrate that t-buOOH causes an oxidant injury in isolated rat lungs that can be potentiated by free iron released from hemoglobin.
Seibert
A F
AF
Department of Medicine, University of South Alabama, Mobile 36617.
Taylor
A E
AE
Bass
J B
JB
Haynes
J
J
D000818:Animals; D001059:Apoproteins / Q000502:physiology; D002199:Capillary Permeability / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D010084:Oxidation-Reduction; D010545:Peroxides / Q000009:adverse effects*; D051381:Rats; D013858:Thiobarbiturates / Q000378:metabolism; D014168:Transferrin / Q000502:physiology; D020122:tert-Butylhydroperoxide
D001059:Apoproteins; C045076:Fenton's reagent; D006454:Hemoglobins; D008563:Membrane Lipids; D010545:Peroxides; D013858:Thiobarbiturates; D014168:Transferrin; C028284:apotransferrin; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D007501:Iron