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Inflammation and airway hyperresponsiveness after chlorine exposure are prolonged by Nrf2 deficiency in mice.
- Source :
-
Free Radical Biology & Medicine . Jan2017, Vol. 102, p1-15. 15p. - Publication Year :
- 2017
-
Abstract
- Rationale Chlorine gas (Cl 2 ) is a potent oxidant and trigger of irritant induced asthma. We explored NF-E2–related factor 2 (Nrf2)-dependent mechanisms in the asthmatic response to Cl 2 , using Nrf2 -deficient mice, buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis and sulforaphane (SFN), a phytochemical regulator of Nrf2. Methods Airway inflammation and airway hyperresponsiveness (AHR) were assessed 24 and 48 h after a 5-min nose-only exposure to 100 ppm Cl 2 of Nrf2 -deficient and wild type Balb/C mice treated with BSO or SFN. Animals were anesthetized, paralyzed and mechanically ventilated (FlexiVent™) and challenged with aerosolized methacholine. Bronchoalveolar lavage (BAL) was performed and lung tissues were harvested for assessment of gene expression. Results Cl 2 exposure induced a robust AHR and an intense neutrophilic inflammation that, although similar in Nrf2 -deficient mice and wild-type mice at 24 h after Cl 2 exposure, were significantly greater at 48 h post exposure in Nrf2 -deficient mice. Lung GSH and mRNA for Nrf2 -dependent phase II enzymes (NQO-1 and GPX2) were significantly lower in Nrf2 -deficient than wild-type mice after Cl 2 exposure. BSO reduced GSH levels and promoted Cl 2 -induced airway inflammation in wild-type mice, but not in Nrf2 -deficient mice, whereas SFN suppressed Cl 2 -induced airway inflammation in wild-type but not in Nrf2- deficient mice. AHR was not affected by either BSO or SFN at 48 h post Cl 2 exposure. Conclusions Nrf2-dependent phase II enzymes play a role in the resolution of airway inflammation and AHR after Cl 2 exposure. Moderate deficiency of GSH affects the magnitude of acute inflammation but not AHR. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08915849
- Volume :
- 102
- Database :
- Academic Search Index
- Journal :
- Free Radical Biology & Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 120524091
- Full Text :
- https://doi.org/10.1016/j.freeradbiomed.2016.11.017