title: The oxidants hypochlorite and hydrogen peroxide induce distinct patterns of acute lung injury.
abstract: Oxidative stress due to activated neutrophils, macrophages and endothelial cells plays a crucial role in acute lung injury. This study compares the effects of the nonradical oxidants hypochlorite (HOCl) and hydrogen peroxide (H2O2) on pulmonary artery pressure [PAPtorr], capillary filtration coefficient (Kf,c), tissue lipid peroxidation (LPO) and reduced glutathione (GSH) depletion. HOCl, H2O2 (1000 nmol min(-1)) or buffer (control) is infused into isolated rabbit lungs. PAP, K(f,c) and lung weight were measured. Experiments were terminated after 105 min or when fluid retention exceeded 50 g. Lung tissue was analyzed for LPO products and GSH. The oxidants induced comparable maximum effects. However, the patterns of lung injury were distinct: H2O2 infusion evoked an early biphasic pressure response (DeltaPAPmax 2.8+/-0.22/4.2+/-0.37 after 5.7+/-1.4/39+/-4.0 min) and a sixfold increase in Kf,c after 90 min. HOCl application caused a late pressure response (DeltaPAPmax 7.6+/-1.7 after 50.6+/-3.7 min) and a sevenfold increase in Kf,c after 60 min. H2O2-induced effects were attenuated by desferal. This may suggest an involvement of transition metal catalysed hydroxyl radical formation. Different oxidants induced distinct patterns of changes in PAP and Kf,c , which are accompanied by a comparable accumulation of LPO products and by a distinct degree of GSH depletion.
authors.affiliation: Department of Pulmonary Medicine, Critical Care and Cardiology, University Leipzig, Leipzig, Germany. stefan.hammerschmidt@t-online.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Hammerschmidt
authors.forename: Hans
authors.initials: H
authors.lastname: Wahn
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006997:Hypochlorous Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D016877:Oxidants / Q000494:pharmacology*; D011817:Rabbits; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D016877:Oxidants; D013438:Sulfhydryl Compounds; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D005978:Glutathione