title: Glutathione modulation during sensitization as well as challenge phase regulates airway reactivity and inflammation in mouse model of allergic asthma.
abstract: 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.
authors.affiliation: Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Electronic address: anadeem@ksu.edu.sa.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Nadeem
authors.affiliation: Amity Institute of Biotechnology, Amity University, Noida, India.
authors.forename: Nahid
authors.initials: N
authors.lastname: Siddiqui
authors.affiliation: Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Naif O
authors.initials: NO
authors.lastname: Alharbi
authors.affiliation: Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohammad M
authors.initials: MM
authors.lastname: Alharbi
authors.affiliation: Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Faisal
authors.initials: F
authors.lastname: Imam
authors.affiliation: Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Sayed-Ahmed
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001249:Asthma / Q000150:complications / Q000276:immunology* / Q000378:metabolism*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism*; D006967:Hypersensitivity / Q000150:complications*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019255:NADPH Oxidases / Q000235:genetics; D016877:Oxidants / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016877:Oxidants; D017382:Reactive Oxygen Species; D019328:Buthionine Sulfoximine; D019255:NADPH Oxidases; D005978:Glutathione
keywords: Antioxidants; Asthma; Glutathione; NADPH oxidase; Reactive oxygen species