Hodono, S., Shimokawa, A., Stewart, N.J. orcid.org/0000-0001-8358-394X et al. (6 more authors) (2018) Ethyl pyruvate improves pulmonary function in mice with bleomycin-induced lung injury as monitored with hyperpolarized 129Xe MR imaging. Magnetic Resonance in Medical Sciences, 17 (4). pp. 331-337. ISSN 1347-3182
Abstract
Purpose: High Mobility Group Box1 (HMGB1), which is one of the damage-associated molecular pattern molecules relating to various inflammatory diseases, has gained interest as a therapeutic target because of its involvement in wound healing processes. In the present study, we investigated HMGB1 as a potential therapeutic target in a model of lung fibrosis using a preclinical hyperpolarized 129Xe (HPXe) MRI system.
Methods: Lung injury was induced by intra-peritoneal injection of bleomycin (BLM) in 19 mice. Three weeks post-injection (when fibrosis was confirmed histologically), administration of ethyl pyruvate (EP) and alogliptin (ALG), which are down- and up-regulators of HMGB1, respectively, was commenced in six and seven of the 19 mice, respectively, and continued for a further 3 weeks. A separate sham-instilled group was formed of five mice, which were administered with saline for 6 weeks. Over the second 3-week period, the effects of disease progression and pharmacological therapy in the four groups of mice were monitored by HPXe MRI metrics of fractional ventilation and gas-exchange function.
Results: Gas-exchange function in BLM mice was significantly reduced after 3 weeks of BLM challenge compared to sham-instilled mice (P < 0.05). Ethyl pyruvate was found to improve HPXe MRI metrics of both ventilation and gas exchange, and repair tissue damage (assessed histologically), to a similar level as sham-instilled mice (P < 0.05), whilst ALG treatment caused no significant improvement of pulmonary function.
Conclusion: This study demonstrates the down-regulator of HMGB1, EP, as a potential therapeutic agent for pulmonary fibrosis, as assessed by a non-invasive HPXe MRI protocol.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 Japanese Society for Magnetic Resonance in Medicine. This work is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives International License. (https://creativecommons.org/licenses/by-nc-nd/4.0/) |
Keywords: | ethyl pyruvate; High Mobility Group Box1; hyperpolarized 129Xe magnetic resonance imaging; murine bleomycin-induced lung fibrosis; therapeutic target |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 29 Apr 2020 14:15 |
Last Modified: | 30 Apr 2020 13:44 |
Status: | Published |
Publisher: | Japanese Society for Magnetic Resonance in Medicine |
Refereed: | Yes |
Identification Number: | 10.2463/mrms.mp.2017-0163 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:159742 |