Ethyl Pyruvate Improves Pulmonary Function in Mice with Bleomycin-induced Lung Injury as Monitored with Hyperpolarized 129Xe MR Imaging
| Autor: | Akihiro Shimokawa, Yukiko Yamauchi, Atsuomi Kimura, Hirohiko Imai, Neil J. Stewart, Mami Yamane, Shota Hodono, Hideaki Fujiwara, Renya Nishimori |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
business.industry medicine.medical_treatment Lung injury Pharmacology medicine.disease Bleomycin Pulmonary function testing 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology chemistry Fibrosis Pulmonary fibrosis medicine Breathing Radiology Nuclear Medicine and imaging business Saline Alogliptin |
| Zdroj: | Magnetic Resonance in Medical Sciences. 17:331-337 |
| ISSN: | 1880-2206 1347-3182 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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