1. Therapeutic effects of C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO-Me; bardoxolone methyl) on radiation-induced lung inflammation and fibrosis in mice.
- Author
-
Wang YY, Zhang CY, Ma YQ, He ZX, Zhe H, and Zhou SF
- Subjects
- Animals, Bronchoalveolar Lavage Fluid chemistry, Collagen metabolism, Cytokines genetics, Cytokines metabolism, Cytoprotection, Disease Models, Animal, Female, Gene Expression Regulation, Hydroxyproline metabolism, Inflammation Mediators metabolism, Lung metabolism, Lung pathology, Lung radiation effects, Lung Injury genetics, Lung Injury metabolism, Lung Injury pathology, Mice, Inbred C57BL, Oleanolic Acid pharmacology, Pulmonary Fibrosis genetics, Pulmonary Fibrosis metabolism, Pulmonary Fibrosis pathology, RNA, Messenger metabolism, Radiation Pneumonitis genetics, Radiation Pneumonitis metabolism, Radiation Pneumonitis pathology, Anti-Inflammatory Agents pharmacology, Lung drug effects, Lung Injury prevention & control, Oleanolic Acid analogs & derivatives, Pulmonary Fibrosis prevention & control, Radiation Pneumonitis prevention & control
- Abstract
The C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO-Me), one of the synthetic triterpenoids, has been found to have potent anti-inflammatory and anticancer properties in vitro and in vivo. However, its usefulness in mitigating radiation-induced lung injury (RILI), including radiation-induced lung inflammation and fibrosis, has not been tested. The aim of this study was to explore the therapeutic effect of CDDO-Me on RILI in mice and the underlying mechanisms. Herein, we found that administration of CDDO-Me improved the histopathological score, reduced the number of inflammatory cells and concentrations of total protein in bronchoalveolar lavage fluid, suppressed secretion and expression of proinflammatory cytokines, including transforming growth factor-β and interleukin-6, elevated expression of the anti-inflammatory cytokine interleukin-10, and downregulated the mRNA level of profibrotic genes, including for fibronectin, α-smooth muscle actin, and collagen I. CDDO-Me attenuated radiation-induced lung inflammation. CDDO-Me also decreased the Masson's trichrome stain score, hydroxyproline content, and mRNA level of profibrotic genes, and blocked radiation-induced collagen accumulation and fibrosis. Collectively, these findings suggest that CDDO-Me ameliorates radiation-induced lung inflammation and fibrosis, and this synthetic triterpenoid is a promising novel therapeutic agent for RILI. Further mechanistic, efficacy, and safety studies are warranted to elucidate the role of CDDO-Me in the management of RILI.
- Published
- 2015
- Full Text
- View/download PDF