Please note that we have stopped the regular imports of Gene Expression Omnibus (GEO) data into ArrayExpress. This may not be the latest version of this experiment.
E-GEOD-50836 - Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease
Released on 13 November 2013, last updated on 25 November 2013
For the clinical treatment of chronic obstructive pulmonary disease (COPD), it is important not only to improve the airflow limitation by bronchodilation but also to suppress emphysema by controlling inflammation. In this study, we have screened for compounds that prevent elastase-induced airspace enlargement in mice from medicines already used clinically. Mepenzolate bromide, a muscarinic antagonist used to treat gastrointestinal disorders was selected. Intratracheal administration or inhalation of mepenzolate bromide decreased the severity of elastase-induced airspace enlargement, alteration of lung mechanics and respiratory dysfunction. While mepenzolate bromide showed bronchodilatory activity, most of other muscarinic antagonists tested did not improve the elastase-induced pulmonary disorders. Mepenzolate bromide suppressed elastase-induced pulmonary inflammatory responses and production of superoxide anions, and reduced the level of cigarette smoke-induced airspace enlargement and alteration of lung mechanics. Based on these results, we propose that this drug is therapeutically effective for COPD as a consequence of both its anti-inflammatory and bronchodilatory activities. In order to understand the mechanism governing mepenzolate-dependent decrease in inflammatory responses and oxidative stress, we performed DNA microarray analysis at the lung of mepenzolate-administered (or control) mice. We then analyzed gene sets that were differently expressed at 25 hours after administration of mepenzolate using Gene Set Enrichment Analysis (GSEA).
transcription profiling by array
Daisuke Kobayashi, Hidekazu Suzuki, Hiroshi Tanaka, Kaoru Mogushi, Kayoko Tahara, Keizo Sato, Ken-ichiro Tanaka, Kumiko Iijima, Naoki Yamakawa, Tohru Mizushima, Tomoaki Ishihara, Toshifumi Sugizaki, Yasunobu Yamashita
Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease. Tanaka K, Ishihara T, Sugizaki T, Kobayashi D, Yamashita Y, Tahara K, Yamakawa N, Iijima K, Mogushi K, Tanaka H, Sato K, Suzuki H, Mizushima T. , PMID:24189798