title: Perfluorochemical liquids enhance delivery of superoxide dismutase to the lungs of juvenile rabbits.
abstract: Previous studies suggest acute lung injury (ALI) in premature newborns is associated with relative deficiency of antioxidant enzymes that may be ameliorated by recombinant human superoxide dismutase (rhSOD). Perfluorochemicals (PFCs) are distributed homogeneously and support gas exchange in diseased lungs. We investigated whether PFCs could provide an effective delivery system for rhSOD. Juvenile rabbits were lung-lavaged, treated with surfactant, and randomized: group I: fluorescently labeled rhSOD (5 mg/kg in 2 mL/kg saline); group II: fluorescently labeled rhSOD (5 mg/kg in 18 mL/kg PFC). Animals were ventilated with oxygen for 4 h; the lungs were harvested for analysis of SOD distribution and oxidative injury. Cardiopulmonary indices remained stable and similar between groups. Qualitative assessment (QA) showed a more homogeneous lung SOD distribution in group II and a better histologic profile. QA of lung SOD distribution showed significant increase in SOD concentrations in group II (7.37 +/- 1.54 microg/mg protein) compared with group I (1.65 +/- 0.23 microg/mg protein). Oxidative injury as assessed by normalized protein carbonyl was 149.1 +/- 26.8% SEM in group II compared with 200.5 +/- 7.3% SEM in group I. Plasma SOD was significantly higher in group II. Administration of rhSOD with or without PFCs does not compromise cardiovascular function or impede lung recovery after ALI. PFCs enhance rhSOD delivery to the lungs by 400% while decreasing lung oxidative damage by 25% compared with rhSOD alone. These data suggest that PFCs optimize lung rhSOD delivery and might enhance the beneficial effects of rhSOD in preventing acute and chronic lung injury.
authors.affiliation: Division of Neonatology , Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Luca
authors.initials: L
authors.lastname: Brunelli
authors.forename: Eric
authors.initials: E
authors.lastname: Hamilton
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Davis
authors.forename: Hshi-Chi
authors.initials: HC
authors.lastname: Koo
authors.forename: Ansamma
authors.initials: A
authors.lastname: Joseph
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kazzaz
authors.forename: Marla R
authors.initials: MR
authors.lastname: Wolfson
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Shaffer
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D016503:Drug Delivery Systems; D005466:Fluorocarbons / Q000494:pharmacology*; D008168:Lung / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D008171:Lung Diseases / Q000201:enzymology / Q000628:therapy; D018384:Oxidative Stress / Q000502:physiology; D050050:Protein Carbonylation; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011817:Rabbits; D011897:Random Allocation; D011994:Recombinant Proteins / Q000493:pharmacokinetics*; D013482:Superoxide Dismutase / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D005466:Fluorocarbons; D011994:Recombinant Proteins; D013482:Superoxide Dismutase