Aerosolized bovine lactoferrin reduces lung injury and fibrosis in mice exposed to hyperoxia
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This study investigated the ability of aerosolized bovine lactoferrin (bLF) to protect the lungs from injury induced by chronic hyperoxia. Female CD-1 mice were exposed to hyperoxia (FiO2 = 80 %) for 7 days to induce lung injury and fibrosis. The therapeutic effects of bLF, administered via an aerosol delivery system, on the chronic lung injury induced by this period of hyperoxia were measured by bronchoalveolar lavage, lung histology, cell apoptosis, and inflammatory cytokines in the lung tissues. After exposure to hyperoxia for 7 days, the survival of the mice was significantly decreased to 20 %. The protective effects of bLF against hyperoxia were further confirmed by significant reductions in lung edema, total cell numbers in bronchoalveolar lavage fluid, inflammatory cytokines (IL-1β and IL-6), pulmonary fibrosis, and apoptotic DNA fragmentation. The aerosolized bLF protected the mice from oxygen toxicity and increased the survival fraction to 66.7 % in the hyperoxic model. The results support the use of an aerosol therapy with bLF in intensive care units to reduce oxidative injury in patients with severe hypoxemic respiratory failure or chronic obstructive pulmonary disease.
KeywordsHyperoxic lung injury Lung fibrosis Aerosol therapy Bovine lactoferrin Oxygen toxicity
The authors would like to thank Prof. Jiung-Wang Liao for his help with the pathology analysis and our colleagues (Drs. Yu-Tang Tung, and Cheng-Wei Lai) in the Molecular Embryology & DNA Methylation Laboratory for their help with discussions and technical issues. We also would like to thank the Biostatic Center of China Medical University for assistance with the statistical analysis. This research was supported by grant NSC-95-2313-B-005-012 from the National Science Council, grant COA-97-6.2.1-U1(9) from the Council of Agriculture, and the Ministry of Education, Taiwan, Republic of China, under the aiming top university plan (ATU-101-S-0508).
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