title: Acute glutathione depletion leads to enhancement of airway reactivity and inflammation via p38MAPK-iNOS pathway in allergic mice.
abstract: Glutathione (GSH) plays a major role in allergic airway responses through a variety of mechanism which include direct scavenging of oxidative species, being a reducing equivalent and regulation of cellular signaling through redox sensitive mechanisms. Therefore, the aim of the present study was to evaluate the role of acute GSH depletion on airway reactivity, inflammation and NO signaling in a mouse model of allergic asthma. Buthionine sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase was used for depletion of GSH levels. Acute depletion of GSH with BSO worsened allergen induced airway reactivity and inflammation through increase in nitrosative stress as reflected by increased inducible NO synthase (iNOS) expression, total nitrates and nitrites (NOx), nitrotyrosine, protein carbonyls, and decreased total antioxidant capacity. Treatment with p38 mitogen-activated protein kinase (MAPK) and iNOS inhibitors attenuated the effects of GSH depletion on airway reactivity and inflammation through attenuation of nitrosative stress as evidenced by a decrease in NOx, nitrotyrosine, protein carbonyls and increase in total antioxidant capacity (TAC). In conclusion, these data suggest that acute depletion of glutathione is associated with alteration of airway responses through an increase in nitrosative stress in allergic airways of mice.
authors: Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Electronic address: anadeem@ksu.edu.sa.
authors: A
authors: A
authors: Nadeem
authors: Amity Institute of Biotechnology, Amity University, Noida, India.
authors: N
authors: N
authors: Siddiqui
authors: Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors: Naif O
authors: NO
authors: Alharbi
authors: Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors: M M
authors: MM
authors: Alharbi
authors: Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors: F
authors: F
authors: Imam
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D019328:Buthionine Sulfoximine / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors; D005978:Glutathione / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D015538:Nitrosation; D010084:Oxidation-Reduction / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D019328:Buthionine Sulfoximine; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione
keywords: Asthma; Glutathione; Inducible nitric oxide synthase; Mitogen-activated protein kinase; Nitrosative stress