Ability of antioxidant liposomes to prevent acute and progressive pulmonary injury.
We recently showed that acute oxidant-related lung injury (ALI) in rats after application of 2-chloroethyl ethyl sulfide (CEES) is attenuated by the airway instillation of antioxidants. We investigated whether intratracheal administration of antioxidant-containing liposomes immediately after instillation of CEES would attenuate short-term as well as long-term (fibrotic) effects of CEES-induced lung injury. In the acute injury model (4 h after injury), N-acetylcysteine (NAC)-containing liposomes were protective and reduced to baseline levels both the lung permeability index and the appearance of proinflammatory mediators in bronchoalveolar lavage fluids from CEES-exposed lungs. Similar results were obtained when rat alveolar macrophages were incubated in vitro with either CEES or lipopolysaccharide in the presence of NAC-liposomes. When lung fibrosis 3 weeks after CEES was quantitated by using hydroxyproline content, liposomes containing NAC or NAC + glutathione had no effects, but liposomes containing alpha/gamma-tocopherol alone or with NAC significantly suppressed the increase in lung hydroxyproline. The data demonstrate that delivery of antioxidants via liposomes to CEES-injured lungs is, depending on liposomal content, protective against ALI, prevents the appearance of proinflammatory mediators in bronchoalveolar fluids, and suppresses progressive fibrosis. Accordingly, the liposomal strategy may be therapeutically useful in CEES-induced lung injury in humans.
Hoesel
Laszlo M
LM
Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
Flierl
Michael A
MA
Niederbichler
Andreas D
AD
Rittirsch
Daniel
D
McClintock
Shannon D
SD
Reuben
Jayne S
JS
Pianko
Matthew J
MJ
Stone
William
W
Yang
Hongsong
H
Smith
Milton
M
Sarma
J Vidya
JV
Ward
Peter A
PA
D000111:Acetylcysteine / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D009151:Mustard Gas / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D024505:Tocopherols / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use
D000975:Antioxidants; D018925:Chemokines; D016207:Cytokines; D016166:Free Radical Scavengers; D008081:Liposomes; C031278:2-chloroethyl ethyl sulfide; D024505:Tocopherols; D009151:Mustard Gas; D000111:Acetylcysteine