bencycloquidium-bromide and Disease-Models--Animal

This study is aimed at exploring the effect of Bencycloquidium bromide (BCQB), a novel M1/M3 receptor antagonist, on mucus secretion in a murine model of allergic rhinitis (AR).. Sprague-Dawley rats were sensitized with ovalbumin to induce AR. After BCQB treatment, nasal symptoms were evaluated. Nasal lavage fluid was used to detect the protein level of cytokines and histamine by the method of enzyme-linked immunosorbent assay. The nasal mucosa of all animals was prepared for western blot, quantitative real-time polymerase chain reaction and histochemical analysis.. BCQB could not only alleviate typical AR symptoms including rhinorrhea, nasal itching and sneezing, but also inhibit the overexpression of mucin 5AC at the level of protein and mRNA. The release of histamine, the mRNA and protein level of IL-6, IL-13 and TNF-α, and the nuclear translocation of NF-κB (p65 and p50) were inhibited by BCQB. In addition, histological studies showed BCQB dramatically inhibited ovalbumin-induced nasal lesions, eosinophil infiltration, aggregation of mast cells, globlet cell hyperplasia and metaplasia.. BCQB attenuates mucus hypersecretion in AR, possibly involving in the NF-κB signaling pathway.

Topics: Animals; Bridged Bicyclo Compounds, Heterocyclic; Cytokines; Disease Models, Animal; Histamine; Male; Nasal Lavage Fluid; Nasal Mucosa; NF-kappa B; Ovalbumin; Rats; Rats, Sprague-Dawley; Receptor, Muscarinic M1; Receptor, Muscarinic M3; Rhinitis, Allergic; Signal Transduction

Bencycloquidium bromide (BCQB), a novel M3 receptor antagonist, alleviates airway hyperresponsiveness, inflammation, and airway remodeling in a murine model of asthma. The aim of this study was to investigate the anti-inflammatory activity of inhaled BCQB in a cigarette smoke (CS)-induced model of acute lung inflammation. Mice exposed to CS developed chronic obstructive pulmonary disease (COPD). Inhalation of BCQB suppressed the accumulation of neutrophils and macrophages in airways and lung and also inhibited the CS-induced increases in mRNA levels of keratinocyte-derived chemokine, monocyte chemotactic protein-1, tumor necrosis factor-alpha, and interleukin-1β in lung and protein expression levels in bronchoalveolar lavage fluid. Moreover, BCQB (300 μg/ml) inhibited the CS-induced changes in superoxide dismutase and myeloperoxidase activities in the lungs. Our study suggests that BCQB might be a potential therapy for inflammation in CS-induced pulmonary diseases, including COPD.

Topics: Administration, Inhalation; Animals; Bridged Bicyclo Compounds, Heterocyclic; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Lung; Mice; Mice, Inbred ICR; Nicotiana; Pneumonia; Receptor, Muscarinic M3; Smoke; Smoking; Treatment Outcome