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Sulforaphane prevents bleomycin?induced pulmonary fibrosis in mice by inhibiting
oxidative stress via nuclear factor erythroid 2?related factor?2 activation
#MMPMID28487960
Yan B
; Ma Z
; Shi S
; Hu Y
; Ma T
; Rong G
; Yang J
Mol Med Rep
2017[Jun]; 15
(6
): 4005-4014
PMID28487960
show ga
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?1?, tumor necrosis factor??, transforming
growth factor?? 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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