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Ability of antioxidant liposomes to prevent acute and progressive pulmonary injury.
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- Author(s): Hoesel LM;Hoesel LM; Flierl MA; Niederbichler AD; Rittirsch D; McClintock SD; Reuben JS; Pianko MJ; Stone W; Yang H; Smith M; Sarma JV; Ward PA
- Source:
Antioxidants & redox signaling [Antioxid Redox Signal] 2008 May; Vol. 10 (5), pp. 973-81.- Publication Type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.- Language:
English - Source:
- Additional Information
- Source: Publisher: Mary Ann Liebert, Inc Country of Publication: United States NLM ID: 100888899 Publication Model: Print Cited Medium: Print ISSN: 1523-0864 (Print) Linking ISSN: 15230864 NLM ISO Abbreviation: Antioxid Redox Signal Subsets: MEDLINE
- Publication Information: Original Publication: Larchmont, NY : Mary Ann Liebert, Inc., 1999-
- Subject Terms: Antioxidants*/chemistry ; Antioxidants*/metabolism ; Antioxidants*/therapeutic use ; Liposomes*/administration & dosage ; Liposomes*/chemistry ; Liposomes*/metabolism ; Liposomes*/therapeutic use; Respiratory Distress Syndrome/*drug therapy ; Respiratory Distress Syndrome/*prevention & control; Acetylcysteine/administration & dosage ; Acetylcysteine/metabolism ; Acetylcysteine/therapeutic use ; Animals ; Bronchoalveolar Lavage Fluid/chemistry ; Chemokines/metabolism ; Cytokines/metabolism ; Free Radical Scavengers/administration & dosage ; Free Radical Scavengers/metabolism ; Free Radical Scavengers/therapeutic use ; Humans ; Lung/cytology ; Lung/drug effects ; Lung/metabolism ; Lung/pathology ; Macrophages, Alveolar/metabolism ; Male ; Mustard Gas/analogs & derivatives ; Mustard Gas/pharmacology ; Rats ; Rats, Long-Evans ; Respiratory Distress Syndrome/chemically induced ; Respiratory Distress Syndrome/pathology ; Tocopherols/administration & dosage ; Tocopherols/metabolism ; Tocopherols/therapeutic use
- Abstract: 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.
- Grant Information: P01 HL031963 United States HL NHLBI NIH HHS; R01 GM029507 United States GM NIGMS NIH HHS; HL 31963 United States HL NHLBI NIH HHS; GM 029507 United States GM NIGMS NIH HHS
- Accession Number: 0 (Antioxidants)
0 (Chemokines)
0 (Cytokines)
0 (Free Radical Scavengers)
0 (Liposomes)
693-07-2 (2-chloroethyl ethyl sulfide)
R0ZB2556P8 (Tocopherols)
T8KEC9FH9P (Mustard Gas)
WYQ7N0BPYC (Acetylcysteine) - Publication Date: Date Created: 20080209 Date Completed: 20080519 Latest Revision: 20220809
- Publication Date: 20240104
- Accession Number: 10.1089/ars.2007.1878
- Accession Number: 18257742
- Source:
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