Open Access

Sulforaphane prevents bleomycin‑induced pulmonary fibrosis in mice by inhibiting oxidative stress via nuclear factor erythroid 2‑related factor‑2 activation

  • Authors:
    • Bingdi Yan
    • Zhongsen Ma
    • Shaomin Shi
    • Yuxin Hu
    • Tiangang Ma
    • Gao Rong
    • Junling Yang
  • View Affiliations

  • Published online on: May 3, 2017     https://doi.org/10.3892/mmr.2017.6546
  • Pages: 4005-4014
  • Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lung fibrosis is associated with inflammation, apoptosis and oxidative damage. The transcription factor nuclear factor erythroid 2‑related factor‑2 (Nrf2) prevents damage to cells from oxidative stress by regulating the expression of antioxidant proteins. Sulforaphane (SFN), an Nrf2 activator, additionally regulates excessive oxidative stress by promoting the expression of endogenous antioxidants. The present study investigated if SFN protects against lung injury induced by bleomycin (BLM). The secondary aim of the present study was to assess if this protection mechanism involves upregulation of Nrf2 and its downstream antioxidants. Pulmonary fibrosis was induced in C57/BL6 mice by intratracheal instillation of BLM. BLM and age‑matched control mice were treated with or without a daily dose of 0.5 mg/kg SFN until sacrifice. On days 7 and 28, mice were assessed for induction of apoptosis, inflammation, fibrosis, oxidative damage and Nrf2 expression in the lungs. The lungs were investigated with histological techniques including haematoxylin and eosin staining, Masson's trichrome staining and terminal deoxynucleotidyl transferase UTP nick end labeling. Inflammatory, fibrotic and apoptotic processes were confirmed by western blot analysis for interleukin‑1β, tumor necrosis factor‑α, transforming growth factor‑β and caspase‑3 protein expressions. Furthermore, protein levels of 3‑nitro‑tyrosine, 4‑hydroxynonenal, superoxide dismutase 1 and catalase were investigated by western blot analysis. It was demonstrated that pulmonary fibrosis induced by BLM significantly increased apoptosis, inflammation, fibrosis and oxidative stress in the lungs at days 7 and 28. Notably, SFN treatment significantly attenuated the infiltration of the inflammatory cells, collagen accumulation, epithelial cell apoptosis and oxidative stress in the lungs. In addition, SFN treatment increased expression of the Nrf2 gene and its downstream targets. In conclusion, these results suggested that SFN treatment of pulmonary fibrosis mouse models may attenuate alveolitis, fibrosis, apoptosis and lung oxidative stress by increasing the expression of antioxidant enzymes, including NAPDH quinone oxidoreductase, heme oxygenase‑1, superoxide dismutase and catalase, via upregulation of Nrf2 gene expression. Thus, the results from the present study may facilitate the development of therapies for BLM‑toxicity and pulmonary fibrosis.
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June-2017
Volume 15 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Yan B, Ma Z, Shi S, Hu Y, Ma T, Rong G and Yang J: Sulforaphane prevents bleomycin‑induced pulmonary fibrosis in mice by inhibiting oxidative stress via nuclear factor erythroid 2‑related factor‑2 activation. Mol Med Rep 15: 4005-4014, 2017
APA
Yan, B., Ma, Z., Shi, S., Hu, Y., Ma, T., Rong, G., & Yang, J. (2017). Sulforaphane prevents bleomycin‑induced pulmonary fibrosis in mice by inhibiting oxidative stress via nuclear factor erythroid 2‑related factor‑2 activation. Molecular Medicine Reports, 15, 4005-4014. https://doi.org/10.3892/mmr.2017.6546
MLA
Yan, B., Ma, Z., Shi, S., Hu, Y., Ma, T., Rong, G., Yang, J."Sulforaphane prevents bleomycin‑induced pulmonary fibrosis in mice by inhibiting oxidative stress via nuclear factor erythroid 2‑related factor‑2 activation". Molecular Medicine Reports 15.6 (2017): 4005-4014.
Chicago
Yan, B., Ma, Z., Shi, S., Hu, Y., Ma, T., Rong, G., Yang, J."Sulforaphane prevents bleomycin‑induced pulmonary fibrosis in mice by inhibiting oxidative stress via nuclear factor erythroid 2‑related factor‑2 activation". Molecular Medicine Reports 15, no. 6 (2017): 4005-4014. https://doi.org/10.3892/mmr.2017.6546