OralN‐acetylcysteine attenuates the rat pulmonary inflammatory response to antigen

Abstract

Oxidative stress is involved in the pathophysiology of inflammatory airway diseases including asthma; therefore, antioxidants might be of clinical benefit in asthma treatment. In the present study, the effects ofN‐acetylcysteine on sensitised brown Norway rats were examined.N‐Acetylcysteine (3 mmol·kg body weight⁻¹administered orally) was given daily for 1 week before challenge and various antigen-induced pulmonary responses were studied.Antigen exposure increased lipid peroxidation in bronchoalveolar lavage fluid (BALF) and oxidised glutathione levels in lung tissue 2 h after challenge. Lung nuclear transcription factor‐κB‐binding activity was increased 2 h after challenge, and BALF tumour necrosis factor‐α and inducible nitric oxide synthase expression in lungs peaked 4 h after challenge. Expression of intercellular adhesion molecule‐1 and mucin MUC5AC was also increased 4 h after challenge. These changes in oxidant status, transcription factor activation, and inflammatory cytokine and gene expression were reduced byN‐acetylcysteine. This thiol did not affect the immediate bronchospasm reaction to antigen in anaesthetised rats but inhibited airways hyperresponsiveness to 5‐hydroxytryptamine and the augmented eosinophil numbers in BALF, which appear 24 h after exposure of conscious rats to antigen aerosol, and abolished antigen-induced extravasation of Evans blue into BALF.These results indicate that oralN‐acetylcysteine exerts an antioxidant protective effect and attenuates pulmonary inflammation in experimental asthma.