Premium
Attenuation of half sulfur mustard gas‐induced acute lung injury in guinea pigs by antioxidant liposomes
Author(s) -
Mukherjee Shyamali,
Stone William L,
Yang Hongsong,
Smith Milton,
Das Salil K
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a261
Subject(s) - liposome , fibrin , sulfur mustard , lung , pharmacology , antioxidant , medicine , antidote , chemistry , biochemistry , toxicity , immunology
No prophylactic treatment is available for lung injury induced by CEES, a mustard gas analog. This study was to develop antidotes for CEES‐induced lung injury. Five antioxidant liposomes were prepared differing in the levels of tocopherol (α, γ, δ̇), N‐acetylcysteine and GSH. A single dose of each liposome was administered intratracheally after 5 and 60 minutes of CEES exposure to guinea pigs. The animals were sacrificed either after 2 h (for lung injury study by leakage of 125 I‐BSA from blood into the lung) or after 30 days (for lung histology study) of CEES exposure. These liposomes offered 9 to 75% protection. The maximum protection was achieved with two liposomes, LIP‐2 (71.5%) and LIP‐4 (75.4%), when administered after 5 minutes of CEES exposure. LIP‐2 differed from LIP‐4 by containing δ‐tocopherol. Delaying the administration of the liposomes to 1h decreased the efficacy. Histological studies indicate that LIP‐2 and LIP‐4 offered significant protection against recruitment of neutrophils, eosinophils, and accumulation of septal and perivascular fibrin and collagen, and parenchymal collapse, which were observed in CEES‐exposed lungs. However, LIP‐2 showed better protection than LIP‐4 in terms of the accumulation of aggregated RBCs, fibrin and collaged in the alveolar space. Thus, LIP‐2 can be used as an effective antidote against CEES–induced lung injury. (Supported by DAMD grant W81XWH‐06‐2‐0044)