Article

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.

Download full-text

Full-text

Available from: William S Powell, Jul 04, 2015
0 Followers
 · 
149 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: New therapeutics designed as rescue treatments after toxic gas injury such as from chlorine (Cl(2)) are an emerging area of interest. We tested the effects of the metalloporphyrin catalytic antioxidant AEOL10150, a compound that scavenges peroxynitrite, inhibits lipid peroxidation, and has SOD and catalase-like activities, on Cl(2)-induced airway injury. Balb/C mice received 100ppm Cl(2) gas for 5 min. Four groups were studied: Cl(2) only, Cl(2) followed by AEOL10150 1 and 9 h after exposure, AEOL10150 only, and control. Twenty-four hours after Cl(2) gas exposure airway responsiveness to aerosolized methacholine (6.25-50mg/ml) was measured using a small-animal ventilator. Bronchoalveolar lavage (BAL) was performed to assess airway inflammation and protein. Whole lung tissue was assayed for 4-hydroxynonenal. In separate groups, lungs were collected at 72 h after Cl(2) injury to evaluate epithelial cell proliferation. Mice exposed to Cl(2) showed a significantly higher airway resistance compared to control, Cl(2)/AEOL10150, or AEOL10150-only treated animals in response to methacholine challenge. Eosinophils, neutrophils, and macrophages were elevated in BAL of Cl(2)-exposed mice. AEOL10150 attenuated the increases in neutrophils and macrophages. AEOL10150 prevented Cl(2)-induced increase in BAL fluid protein. Chlorine induced an increase in the number of proliferating airway epithelial cells, an effect AEOL10150 attenuated. 4-Hydroxynonenal levels in the lung were increased after Cl(2) and this effect was prevented with AEOL10150. AEOL10150 is an effective rescue treatment for Cl(2)-induced airway hyperresponsiveness, airway inflammation, injury-induced airway epithelial cell regeneration, and oxidative stress.
    Free Radical Biology and Medicine 03/2011; 50(5):602-8. DOI:10.1016/j.freeradbiomed.2010.12.001
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It is pointed out that a complete third-order description of a charged particle optical system must include a combined function bending magnet. The magnetic field can have dipole, quadrupole, sextupole, and octupole terms. Midplane symmetry is assumed. Each additional order in the optical analysis requires inclusion of an additional multipole in the field expansion. First-, second-, and third-order expansions require quadrupole, sextupole, and octupole terms, respectively. Third-order matrix elements can be derived by an iterative Green's function solution of the differential equations of motion. Third-order transfer matrix elements arise not only from third-order terms in the equations of motion, but also from the cascading effect of second-order terms. Solutions have been derived and incorporated into the computer program Transport and Turtle
    Particle Accelerator Conference, 1989. Accelerator Science and Technology., Proceedings of the 1989 IEEE; 04/1989
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This paper proposes a DNA algorithm for solving an NP-complete problem (The Shortest Common Superstring Problem) by manipulation of biomolecules, and presents partial results of the experiment that implements our algorithm. We also discuss practical constraints that have to be taken into account when implementing the algorithm, propose a coding system as a solution to these practical restrictions, and discuss the control experiments performed for establishing the parameters controlling the specificity of the assay. 1 Introduction Molecular computing, known also under the name of biomolecular computing, biocomputing or DNA computing, is a new computation paradigm that employs (bio)molecule manipulation to solve computational problems. The excitement generated by the first successful experiment (Adleman 1994, [1]) was due to the fact that computing with biomolecules (mainly DNA) offered an entirely new way of performing and looking at computations: the main idea was that data could be ...
    International Journal of Artificial Intelligence Tools 04/1999; DOI:10.1109/IJSIS.1998.685431

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.