Modulation of airway hyperresponsiveness by thiols in a murine in vivo model of allergic asthma.
OBJECTIVE
Since oxidative stress contributes to the pathogenesis of asthma, this study addressed the question whether supplementing the endogenous antioxidant, glutathione (GSH), would alleviate features of allergic asthma in the mouse.


METHODS
Ovalbumin-sensitized mice received aerosols of the GSH-donors, glutathione-ethyl ester (GSEt) or N-acetylcysteine, before or during respiratory allergen challenges, or during methacholine challenges given one day after the last allergen challenge. Lung GSH levels were measured shortly after allergen or methacholine challenge. In addition, the effect of GSH supplements on airway hyperresponsiveness and inflammatory cell numbers in the airway lumen was assessed.


RESULTS
GSEt decreased allergen-induced airway hyperresponsiveness when given in combination with methacholine. However, when given before or during allergen challenge, both GSH-donors failed to decrease the methacholine-induced airway contractility, change cell numbers in the airway lumen, or increase lung GSH levels. In addition, allergen challenges of sensitized mice did not decrease lung GSH levels.


CONCLUSIONS
In contrast to guinea pigs and humans, allergen challenges in mice does not lead to acute oxidative stress.
Kloek
J
J
Department of Pharmacology and Pathophysiology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
Van Ark
I
I
De Clerck
F
F
Bloksma
N
N
Nijkamp
F P
FP
Folkerts
G
G
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005100:Expectorants / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018721:Muscarinic Agonists / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D005100:Expectorants; D018721:Muscarinic Agonists; D013438:Sulfhydryl Compounds; D016210:Methacholine Chloride; C042431:S-ethyl glutathione; D010047:Ovalbumin; D005978:Glutathione; D000111:Acetylcysteine