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Ethyl Pyruvate Improves Pulmonary Function in Mice with Bleomycin-induced Lung Injury as Monitored with Hyperpolarized <sup>129</sup>Xe MR Imaging
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- Hodono Shota
- Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University
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- Shimokawa Akihiro
- Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University
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- Stewart Neil J.
- Division of Bioengineering and Bioinformatics, Graduate School of Information Science and Technology, Hokkaido University
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- Yamauchi Yukiko
- Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University
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- Nishimori Renya
- Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University
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- Yamane Mami
- Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University
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- Imai Hirohiko
- Department of Systems Science, Graduate School of Informatics, Kyoto University
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- Fujiwara Hideaki
- Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University
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- Kimura Atsuomi
- Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University
Bibliographic Information
- Other Title
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- Ethyl Pyruvate Improves Pulmonary Function in Mice with Bleomycin-induced Lung Injury as Monitored with Hyperpolarized
- Ethyl pyruvate improves pulmonary function in mice with bleomycin-induced lung injury as monitored with hyperpolarized 129Xe MR imaging
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Description
<p>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.</p><p>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.</p><p>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.</p><p>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.</p>
Journal
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- Magnetic Resonance in Medical Sciences
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Magnetic Resonance in Medical Sciences 17 (4), 331-337, 2018
Japanese Society for Magnetic Resonance in Medicine
