Dimethylthiourea protects against chlorine induced changes in airway function in a murine model of irritant induced asthma

Meakins Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec, Canada.
Respiratory research (Impact Factor: 3.38). 10/2010; 11(1):138. DOI: 10.1186/1465-9921-11-138
Source: PubMed

ABSTRACT Exposure to chlorine (Cl2) causes airway injury, characterized by oxidative damage, an influx of inflammatory cells and airway hyperresponsiveness. We hypothesized that Cl2-induced airway injury may be attenuated by antioxidant treatment, even after the initial injury.
Balb/C mice were exposed to Cl2 gas (100 ppm) for 5 mins, an exposure that was established to alter airway function with minimal histological disruption of the epithelium. Twenty-four hours after exposure to Cl2, airway responsiveness to aerosolized methacholine (MCh) was measured. Bronchoalveolar lavage (BAL) was performed to determine inflammatory cell profiles, total protein, and glutathione levels. Dimethylthiourea (DMTU;100 mg/kg) was administered one hour before or one hour following Cl2 exposure.
Mice exposed to Cl2 had airway hyperresponsiveness to MCh compared to control animals pre-treated and post-treated with DMTU. Total cell counts in BAL fluid were elevated by Cl2 exposure and were not affected by DMTU treatment. However, DMTU-treated mice had lower protein levels in the BAL than the Cl2-only treated animals. 4-Hydroxynonenal analysis showed that DMTU given pre- or post-Cl2 prevented lipid peroxidation in the lung. Following Cl2 exposure glutathione (GSH) was elevated immediately following exposure both in BAL cells and in fluid and this change was prevented by DMTU. GSSG was depleted in Cl2 exposed mice at later time points. However, the GSH/GSSG ratio remained high in chlorine exposed mice, an effect attenuated by DMTU.
Our data show that the anti-oxidant DMTU is effective in attenuating Cl2 induced increase in airway responsiveness, inflammation and biomarkers of oxidative stress.

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Available from: William S Powell, Jul 04, 2015
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Questions & Answers about this publication

  • Toby K Mcgovern added an answer in Oxidative Stress:
    What factors effect oxidative stress in diseases?
    I have studied a lot about oxidative stress in COPD and asthma and have heard a bit about its induction during environmental factors. For e.g. the heat of cold induces it. Actually, I don't know the molecular mechanism. Cancer cells have high oxidative stress too.
    Toby K Mcgovern · McGill University
    Here is another publication regarding the effects of oxidative stress on airway injury.