Journal
BIOMATERIALS
Volume 35, Issue 24, Pages 6553-6562Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.04.049
Keywords
Antioxidant; Fibrosis; Inflammation; Liposome; Lung
Funding
- Health Sciences Research Grants from the Ministry of Health, Labour and Welfare of Japan [201208035]
- Japan Society for the Promotion of Science (JSPS) [KAKENHI 24790159]
- Grants-in-Aid for Scientific Research [25670085, 24790159] Funding Source: KAKEN
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Carbon monoxide (CO) has potent anti-inflammatory and anti-oxidant effects. We report herein on the preparation of a nanotechnology-based CO donor, CO-bound hemoglobin-vesicles (CO-HbV). We hypothesized that CO-HbV could have a therapeutic effect on idiopathic pulmonary fibrosis (IPF), an incurable lung fibrosis, that is thought to involve inflammation and the production of reactive oxygen species (ROS). Pulmonary fibril formation and respiratory function were quantitatively evaluated by measuring hydroxyproline levels and forced vital capacity, respectively, using a bleomycin-induced pulmonary fibrosis mice model. CO-HbV suppressed the progression of pulmonary fibril formation and improved respiratory function compared to saline and HbV. The suppressive effect of CO-HbV on pulmonary fibrosis can be attributed to a decrease in ROS generation by inflammatory cells, NADPH oxidase 4 and the production of inflammatory cells, cytokines and transforming growth factor-beta in the lung. This is the first demonstration of the inhibitory effect of CO-HbV on the progression of pulmonary fibrosis via the anti-oxidative and anti-inflammatory effects of CO in the bleomycin-induced pulmonary fibrosis mice model. CO-HbV has the potential for use in the treatment of, not only IPF, but also a variety of other ROS and inflammation-related disorders. (C) 2014 Elsevier Ltd. All rights reserved.
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