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Effects of intranasal azithromycin on features of cigarette smoke-induced lung inflammation

European journal of pharmacology(2022)

Cited 10|Views18
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Abstract
Airflow limitation in chronic obstructive pulmonary disease (COPD) is the result of exaggerated airway fibrosis and obliteration of the small airways due to persistent inflammation, and an impaired anti-oxidant response. EMT has been implicated as an active signalling process in cigarette smoke (CS)-induced lung pathology, and macrolide Azithromycin (AZT) use has gained interest in treating COPD. Here, we tested effectiveness of intra-nasal AZT alone and in combination with dexamethasone (DEX) on CS-induced acute lung inflammation. Human alveolar epithelial cells (A549) were treated with CS extract (CSE) for 48 h, and male Balb/c mice were exposed to CS (3 cigarettes-3 times/day) for 4 days. The effects of AZT alone (0.25 and 1.25 mu M, in vitro; 0.5 and 5 mg/kg, in vivo) or in combination with DEX (1 mu M, in vitro; 1 mg/kg, in vivo) on CS-induced cellular cytotoxicity, oxidative stress, inflammation, and lung function were assessed. AZT alone and in combination with DEX significantly inhibited the CS (E)-induced expression of mesenchymal protein markers and the regulatory protein beta-catenin. Furthermore, AZT by itself or in combination with DEX significantly suppressed CS-induced expression of the proinflammtory cytokines TNF alpha, IL1 beta and IL6 and prevented pNFkB. Mechanistically, AZT restored the CS-induced reduction in anti-oxidant transcription factor NRF2 and upregulated HDAC2 levels, thereby repressing inflammatory gene expression. Beneficial effects of AZT functionally translated in improved lung mechanics in vivo. Further preclinical and clinical studies are warranted to fully establish and validate the therapeutic efficacy of AZT as a mono- or combination therapy for the treatment of COPD.
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Key words
Cigarette smoke,Inflammation,Oxidative stress,Acute lung inflammation
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