Ability of Antioxidant Liposomes to Prevent Acute and Progressive Pulmonary Injury
| Autor: | Matthew J. Pianko, Andreas D. Niederbichler, Milton G. Smith, Jayne S. Reuben, Shannon D. McClintock, Michael A. Flierl, J. Vidya Sarma, Hongsong Yang, Peter A. Ward, William L. Stone, Daniel Rittirsch, Laszlo M. Hoesel |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Pathology medicine.medical_specialty Lipopolysaccharide Physiology Clinical Biochemistry Tocopherols Lung injury Pharmacology Biochemistry Antioxidants Proinflammatory cytokine Hydroxyproline chemistry.chemical_compound Fibrosis Macrophages Alveolar Mustard Gas medicine Animals Humans Rats Long-Evans Lung Molecular Biology General Environmental Science Respiratory Distress Syndrome Liposome medicine.diagnostic_test business.industry Free Radical Scavengers Cell Biology respiratory system medicine.disease Acetylcysteine Rats respiratory tract diseases Bronchoalveolar lavage medicine.anatomical_structure chemistry Liposomes Cytokines General Earth and Planetary Sciences Chemokines business Bronchoalveolar Lavage Fluid hormones hormone substitutes and hormone antagonists |
| Zdroj: | Antioxidants & Redox Signaling. 10:963-972 |
| ISSN: | 1557-7716 1523-0864 |
| DOI: | 10.1089/ars.2007.1878 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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