Ameliorative Effect of Mepenzolate Bromide against Pulmonary Fibrosis
| Autor: | Teita Asano, Arata Azuma, Tomomi Niino, Toshifumi Sugizaki, Hidekazu Suzuki, Ken Ichiro Tanaka, Tohru Mizushima, Shota Kurotsu |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
Pathology medicine.medical_specialty Pulmonary Fibrosis Vital Capacity Cell Count Lung injury Pharmacology Benzilates Bleomycin Transforming Growth Factor beta1 Mice chemistry.chemical_compound Idiopathic pulmonary fibrosis Piperidines Fibrosis Pulmonary fibrosis medicine Animals Respiratory function Myofibroblasts Mepenzolate Lung Lung Compliance Glutathione Transferase Inflammation Cell Death business.industry NADPH Oxidases respiratory system medicine.disease respiratory tract diseases Oxygen Hydroxyproline medicine.anatomical_structure chemistry Molecular Medicine business Bronchoalveolar Lavage Fluid medicine.drug |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 350:79-88 |
| ISSN: | 1521-0103 0022-3565 |
| DOI: | 10.1124/jpet.114.213009 |
| Popis: | Idiopathic pulmonary fibrosis is thought to involve lung injury caused by reactive oxygen species (ROS), which in turn is followed by abnormal fibrosis. A transforming growth factor (TGF)-β1-induced increase in myofibroblast number plays an important role in this abnormal fibrosis. We recently found that mepenzolate bromide (mepenzolate), which has been used clinically to treat gastrointestinal disorders, has ROS-reducing properties. In the present study, we examined the effect of mepenzolate on bleomycin-induced pulmonary fibrosis and lung dysfunction in mice. The severity of pulmonary fibrosis was assessed by histopathologic evaluation and determination of hydroxyproline levels. Lung mechanics (elastance) and respiratory function [forced vital capacity (FVC)] were assessed using a computer-controlled ventilator. Respiratory function was also evaluated by monitoring percutaneous arterial oxygen saturation (SpO2). Intratracheal administration of mepenzolate prior to bleomycin treatment reduced the extent of pulmonary fibrosis and changes in lung mechanics and led to a significant recovery of both FVC and SpO2 compared with control. Furthermore, mepenzolate produced a therapeutic effect even when it was administered after the development of fibrosis. Administration of mepenzolate also prevented bleomycin-induced pulmonary cell death and inflammatory responses and increased myofibroblast number. Mepenzolate also decreased NADPH oxidase activity and active TGF-β1 level or increased glutathione S-transferase (GST) activity in the presence of bleomycin treatment. These results show that the intratracheal administration of mepenzolate reduced bleomycin-induced pulmonary fibrosis and lung dysfunction in mice. These effects may be due to this drug's inhibitory effect on NADPH oxidase and TGF-β1 activities and its stimulatory effect on GST. |
| Databáze: | OpenAIRE |
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