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.

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.

• Authors: Yan-Yang Wang, Cui-Ying Zhang, Ya-Qiong Ma, Zhi-Xu He, Hong Zhe, Shu-Feng Zhou
• Journal: Drug design, development and therapy (Drug Des Devel Ther) Vol. 9 Pg. 3163-78 ( 2015) ISSN: 1177-8881 [Electronic] New Zealand
• PMID: 26124639 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Inflammation Mediators
• RNA, Messenger
• Oleanolic Acid
• Collagen
• bardoxolone methyl
• Hydroxyproline

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Bronchoalveolar Lavage Fluid (chemistry)
• Collagen (metabolism)
• Cytokines (genetics, metabolism)
• Cytoprotection
• Disease Models, Animal
• Female
• Gene Expression Regulation
• Hydroxyproline (metabolism)
• Inflammation Mediators (metabolism)
• Lung (drug effects, metabolism, pathology, radiation effects)
• Lung Injury (genetics, metabolism, pathology, prevention & control)
• Mice, Inbred C57BL
• Oleanolic Acid (analogs & derivatives, pharmacology)
• Pulmonary Fibrosis (genetics, metabolism, pathology, prevention & control)
• RNA, Messenger (metabolism)
• Radiation Pneumonitis (genetics, metabolism, pathology, prevention & control)