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Enhanced resistance to oxidative lung injury by an Nrf2‐ARE inducer in mice
Author(s) -
Cho HyeYoun,
MillerDeGraff Laura,
Talalay Paul,
Yamamoto Masayuki,
Kleeberger Steven
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.918.2
Subject(s) - hyperoxia , sulforaphane , antioxidant , oxygen toxicity , oxidative stress , lung , pharmacology , chemistry , inflammation , reactive oxygen species , toxicity , medicine , immunology , biochemistry
Nrf2 is essential in airway protection against oxidative insults via antioxidant response element (ARE)‐mediated induction of antioxidants. To test the hypothesis that enhanced Nrf2‐ARE responsiveness protects lungs from subsequent hyperoxia (>95% O2) exposure, Nrf2+/+ and Nrf2−/− mice were fed with diet containing standardized broccoli sprout extract (SBE) or regular diet for 14 days before air or hyperoxia exposure. In a separate study, the mice were orally treated with sulforaphane (days ‐5, ‐3, ‐1) before hyperoxia exposure. In Nrf2+/+ mice, hyperoxia‐induced lung neutrophilic inflammation, protein edema, and cell necrosis were significantly decreased by SBE treatment. Hyperoxia‐induced body weight loss was significantly attenuated by SBE. Sulforaphane also significantly decreased lung inflammation caused by hyperoxia in these mice. Expression of lung Nrf2 and antioxidant mRNAs was highly elevated in Nrf2+/+ mice by sulforaphane after hyperoxia. SBE enhanced antioxidant expressions in air‐exposed mice but there was no significant effect of SBE after hyperoxia. Lung injury phenotypes of Nrf2−/− mice with suppressed antioxidant expressions were not significantly changed by SBE or sulforaphane treatment after hyperoxia. Results support a preventive role for fortified Nrf2‐ARE pathway in pulmonary oxygen toxicity. Supported by the Intramural Program of NIEHS