OralN‐acetylcysteine attenuates the rat pulmonary inflammatory response to antigen

Abstract

Oral N-acetylcysteine attenuates the rat pulmonary inflammatory response to antigen. S. Blesa, J. Cortijo, M. Mata, A. Serrano, D. Closa, F. Santangelo, J.M. Estrela, J. Suchankova, E.J. Morcillo. #ERS Journals Ltd 2003. 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 of N-acetylcysteine on sensitised brown Norway rats were examined.N-Acetylcysteine (3 mmol?kg body weight -1 administered 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-kB-binding activity was increased 2 h after challenge, and BALF tumour necrosis factor-a 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 by N-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 oral N-acetylcysteine exerts an antioxidant protective effect and attenuates pulmonary inflammation in experimental asthma.

Antioxidant Strategies in the Treatment of Bronchial Asthma

“…A second example of pharmacologically modulating GSH pools involved the glutathione precursor γ-glutamylcysteinylethyl ester (γ-GCE) which was shown to effectively augment reduced cellular glutathione content (GSH) and redox ratio (GSH/GSSG) in antigen presenting cells to limit pro-inflammatory gene induction and attenuate lung inflammation in the ovalbumin model of asthma 12 . Previous studies with cysteine precursors produced similar results but difference in cell permeability were hypothesized to limit overall effectiveness 13,60,61 . A potential advantage of these two strategies is that their therapeutic targets are more selective and focused on glutathione homeostasis itself as compared to the broad array of antioxidant and other cytoprotective genes activated by Nrf2.…”

Modulatory effects of N-acetyl-L-cysteine on human eosinophil apoptosis

“…NAC has proved beneficial in pulmonary diseases linked to oxidative stress [8]. Recent studies from the current authors' laboratory have also demonstrated the capacity of NAC to exert anti-inflammatory effects in an experimental model of allergic asthma [9] and to inhibit the generation of oxidant species from activated human eosinophils [10]. The present study addresses whether spontaneous and cytokine-delayed eosinophil apoptosis may be modulated by a clinically used antioxidant like NAC.…”

N-acetyl-l-cysteine (NAC) inhibit mucin synthesis and pro-inflammatory mediators in alveolar type II epithelial cells infected with influenza virus A and B and with respiratory syncytial virus (RSV)

“…The Nuclear factor kappa B (NF- [33]. Aliquots of nuclear extracts with equal amounts of protein (10 µg) were processed Samples were analysed on a 6% non-denaturating polyacrylamide gel.…”