Effect of 4-[(5,6,7,8-Tetrahydro-5,5,8,8-Tetramethyl-2-Naphthalenyl)Carbamoyl]Benzoic Acid (Am80) on Alveolar Regeneration in Adiponectin Deficient-Mice Showing a Chronic Obstructive Pulmonary Disease–Like Pathophysiology
| Autor: | Mai Hirokawa, Tomomi Akita, Hitomi Sakai, Michiko Horiguchi, Isao Tachibana, Harumi Kumagai, Yoshito Takeda, Yuki Oiso, Norikazu Maeda, Chikamasa Yamashita, Chihiro Ozawa |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Pathology Tetrahydronaphthalenes Retinoic acid Pulmonary disease Benzoates Gastroenterology Mice Pulmonary Disease Chronic Obstructive 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Regeneration Lung volumes Benzoic acid Mice Knockout Pharmacology COPD Adiponectin business.industry Regeneration (biology) medicine.disease Pathophysiology Mice Inbred C57BL Pulmonary Alveoli 030104 developmental biology 030228 respiratory system chemistry Molecular Medicine business |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 361:501-505 |
| ISSN: | 1521-0103 0022-3565 |
| Popis: | Chronic obstructive pulmonary disease (COPD) is an intractable pulmonary disease that causes widespread and irreversible alveolar collapse. Although COPD occurs worldwide, only symptomatic therapy is currently available. Our objective is the development of therapeutic agents to eradicate COPD. Therefore, we focused on 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl) carbamoyl] benzoic acid (Am80), which is a derivative of all-trans retinoic acid. We evaluated the effects of Am80 on alveolar repair in a novel COPD model of adiponectin-deficient mice. This mouse model has more symptoms similar to human COPD than the classic elastase-induced emphysema mouse model. Lung volume, computed tomography (CT) values, low-attenuation area ratios, and bone and fat mass were measured by CT. However, the administration of Am80 did not affect these results. To examine the degree of destruction in the alveoli, the mean linear intercept of the alveolar walls was calculated, and assessment of this value confirmed that there was a significant difference between the control (46.3 ± 2.3 μm) and 0.5 mg/kg Am80-treated group (34.4 ± 1.7 µm). All mice survived the treatment, which lasted for more than 6 months, and we did not observe any abnormalities in autopsies performed at 80 weeks of age. These results suggested that Am80 was effective as a novel therapeutic compound for the treatment of COPD. |
| Databáze: | OpenAIRE |
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