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      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

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          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.

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          Most cited references 59

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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2015
                22 June 2015
                : 9
                : 3163-3178
                Affiliations
                [1 ]Department of Radiation Oncology, General Hospital of Ningxia Medical University, Guiyang, People’s Republic of China
                [2 ]Graduate School, Ningxia Medical University, Guiyang, People’s Republic of China
                [3 ]Department of Pathology, General Hospital of Ningxia Medical University, Guiyang, People’s Republic of China
                [4 ]Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guizhou Medical University, Guiyang, People’s Republic of China
                [5 ]Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, FL, USA
                Author notes
                Correspondence: Hong Zhe, Department of Radiation Oncology, General Hospital of Ningxia Medical University, 804 Shengli Street, Yinchuan, Ningxia 750004, People’s Republic of China, Tel +86 951 674 3315, Fax +86 951 674 6101, Email nxzh1961@ 123456hotmail.com
                Shu-Feng Zhou, Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B Down Boulevard, Tampa, FL 33612, USA, Tel +1 813 974 6276, Fax +1 813 905 9885, Email szhou@ 123456health.usf.edu
                [*]

                These authors contributed equally to this work

                Article
                dddt-9-3163
                10.2147/DDDT.S80958
                4482372
                26124639
                © 2015 Wang et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Original Research

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