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

• Published in: The Journal of pharmacology and experimental therapeutics 2017-06, Vol.361 (3), p.501-505
• Main Authors: Sakai, Hitomi, Horiguchi, Michiko, Akita, Tomomi, Ozawa, Chihiro, Hirokawa, Mai, Oiso, Yuki, Kumagai, Harumi, Takeda, Yoshito, Tachibana, Isao, Maeda, Norikazu, Yamashita, Chikamasa
• Format: Article
• Language: English
• Subjects: Adiponectin - deficiency; Animals; Benzoates - pharmacology; Benzoates - therapeutic use; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Pulmonary Alveoli - drug effects; Pulmonary Alveoli - physiology; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - metabolism; Pulmonary Disease, Chronic Obstructive - physiopathology; Regeneration - drug effects; Regeneration - physiology; Tetrahydronaphthalenes - pharmacology; Tetrahydronaphthalenes - therapeutic use
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.117.240515

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.