Oral N-acetylcysteine attenuates the rat pulmonary inflammatory response to antigen.
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-alpha 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.
Blesa
S
S
Dept of Pharmacology, Faculty of Medicine, University of Valencia, Valencia, Spain.
Cortijo
J
J
Mata
M
M
Serrano
A
A
Closa
D
D
Santangelo
F
F
Estrela
J M
JM
Suchankova
J
J
Morcillo
E J
EJ
D000111:Acetylcysteine / Q000494:pharmacology*; D000284:Administration, Oral; D000403:Airway Resistance / Q000187:drug effects; D000485:Allergens / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology*; D001483:Base Sequence; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase / Q000032:analysis; D052247:Nitric Oxide Synthase Type II; D011336:Probability; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000485:Allergens; D018836:Inflammation Mediators; D018799:Intercellular Adhesion Molecule-1; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000111:Acetylcysteine