Glutathione modulation during sensitization as well as challenge phase regulates airway reactivity and inflammation in mouse model of allergic asthma
Copyright © 2014 Elsevier Masson SAS. All rights reserved..
Glutathione, being a major intracellular redox regulator has been shown to be implicated in regulation of airway reactivity and inflammation. However, no study so far has investigated the effect of glutathione depletion/repletion during sensitization and challenge phases separately, which could provide an important insight into the pathophysiology of allergic asthma. The aim of the present study was to evaluate the role of glutathione depletion/repletion during sensitization and challenge phases separately in a mouse model of allergic asthma. Buthionine sulphoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase or N-acetyl cysteine (NAC), a thiol donor were used for depletion or repletion of glutathione levels respectively during both sensitization and challenge phases separately followed by assessment of airway reactivity, inflammation and oxidant-antioxidant balance in allergic mice. Depletion of glutathione with BSO during sensitization as well as challenge phase worsened allergen induced airway reactivity/inflammation and caused greater oxidant-antioxidant imbalance as reflected by increased NADPH oxidase expression/reactive oxygen species (ROS) generation/lipid peroxides formation and decreased total antioxidant capacity. On the other hand, repletion of glutathione pool by NAC during sensitization and challenge phases counteracted allergen induced airway reactivity/inflammation and restored oxidant-antioxidant balance through a decrease in NADPH oxidase expression/ROS generation/lipid peroxides formation and increase in total antioxidant capacity. Taken together, these findings suggest that depletion or repletion of glutathione exacerbates or ameliorates allergic asthma respectively by regulation of airway oxidant-antioxidant balance. This might have implications towards increased predisposition to allergy by glutathione depleting environmental pollutants.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:103 |
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| Enthalten in: |
Biochimie - 103(2014) vom: 05. Aug., Seite 61-70 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nadeem, Ahmed [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.02.2015 Date Revised 16.11.2017 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.biochi.2014.04.001 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM237459051 |
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| 245 | 1 | 0 | |a Glutathione modulation during sensitization as well as challenge phase regulates airway reactivity and inflammation in mouse model of allergic asthma |
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| 520 | |a Copyright © 2014 Elsevier Masson SAS. All rights reserved. | ||
| 520 | |a Glutathione, being a major intracellular redox regulator has been shown to be implicated in regulation of airway reactivity and inflammation. However, no study so far has investigated the effect of glutathione depletion/repletion during sensitization and challenge phases separately, which could provide an important insight into the pathophysiology of allergic asthma. The aim of the present study was to evaluate the role of glutathione depletion/repletion during sensitization and challenge phases separately in a mouse model of allergic asthma. Buthionine sulphoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase or N-acetyl cysteine (NAC), a thiol donor were used for depletion or repletion of glutathione levels respectively during both sensitization and challenge phases separately followed by assessment of airway reactivity, inflammation and oxidant-antioxidant balance in allergic mice. Depletion of glutathione with BSO during sensitization as well as challenge phase worsened allergen induced airway reactivity/inflammation and caused greater oxidant-antioxidant imbalance as reflected by increased NADPH oxidase expression/reactive oxygen species (ROS) generation/lipid peroxides formation and decreased total antioxidant capacity. On the other hand, repletion of glutathione pool by NAC during sensitization and challenge phases counteracted allergen induced airway reactivity/inflammation and restored oxidant-antioxidant balance through a decrease in NADPH oxidase expression/ROS generation/lipid peroxides formation and increase in total antioxidant capacity. Taken together, these findings suggest that depletion or repletion of glutathione exacerbates or ameliorates allergic asthma respectively by regulation of airway oxidant-antioxidant balance. This might have implications towards increased predisposition to allergy by glutathione depleting environmental pollutants | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Antioxidants | |
| 650 | 4 | |a Asthma | |
| 650 | 4 | |a Glutathione | |
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| 700 | 1 | |a Alharbi, Naif O |e verfasserin |4 aut | |
| 700 | 1 | |a Alharbi, Mohammad M |e verfasserin |4 aut | |
| 700 | 1 | |a Imam, Faisal |e verfasserin |4 aut | |
| 700 | 1 | |a Sayed-Ahmed, Mohamed M |e verfasserin |4 aut | |
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