Mitigation of radiation-induced pulmonary fibrosis by small-molecule dye IR-780.

Abstract

Radiation-induced pulmonary fibrosis (RIPF) is a common complication during thoracic radiotherapy, but there are few effective treatments. Here, we identify IR-780, a mitochondria-targeted near-infrared (NIR) dye, can selectively accumulate in the irradiated lung tissues. Besides, IR-780 significantly alleviates radiation-induced acute lung injury and fibrosis. Furthermore, our results show that IR-780 prevents the differentiation of fibroblasts and the release of pro-fibrotic factors from alveolar macrophages induced by radiation. Besides, IR-780 downregulates the expression of glycolysis-associated genes, and 2-Deoxy-d-glucose (2-DG) also prevents the development of fibrosis in vitro, suggesting radioprotective effects of IR-780 on RIPF might be related to glycolysis regulation. Finally, IR-780 induces tumour cell apoptosis and enhances radiosensitivity in representative H460 and A549 cell lines. These findings indicate that IR-780 is a potential therapeutic small-molecule dye during thoracic radiotherapy.

• Authors: Min Luo, Long Chen, Jiancheng Zheng, Qing Wang, Yu Huang, Fengying Liao, Zhongyong Jiang, Chi Zhang, Gufang Shen, Jie Wu, Yang Wang, Yawei Wang, Yu Leng, Shiqian Han, Aihua Zhang, Ziwen Wang, Chunmeng Shi
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 164 Pg. 417-428 (02 20 2021) ISSN: 1873-4596 [Electronic] United States
• PMID: 33418112 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• 2-(2-(2-chloro-3-((1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-3,3-dimethyl-1-propylindolium
• Indoles

Topics

• A549 Cells
• Animals
• Humans
• Indoles
• Lung
• Mice
• Mice, Inbred C57BL
• Pulmonary Fibrosis (etiology, genetics)
• Radiation Injuries