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. 2017

Hitomi Sakai, and Michiko Horiguchi, and Tomomi Akita, and Chihiro Ozawa, and Mai Hirokawa, and Yuki Oiso, and Harumi Kumagai, and Yoshito Takeda, and Isao Tachibana, and Norikazu Maeda, and Chikamasa Yamashita
Department of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences (H.S., M.Ho., T.A., C.O., M.Hi., O.Y., H.K., C.Y.), and Fusion of Regenerative Medicine with DDS, Research Institute for Science and Technology (M.Ho., C.Y.), Tokyo University of Science, Chiba; Respiratory Medicine, Allergy and Rheumatic Diseases (Y.T., I.T., N.M.), and Department of Metabolism and Atherosclerosis (N.M.), Graduate School of Medicine, Osaka University, Osaka; Department of Medicine, Nissay Hospital, Nippon Life Saiseikai Public Interest Incorporated Foundation, Osaka (I.T.), Japan.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D011650 Pulmonary Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Alveoli, Pulmonary,Alveolus, Pulmonary,Pulmonary Alveolus
D012038 Regeneration The physiological renewal, repair, or replacement of tissue. Endogenous Regeneration,Regeneration, Endogenous,Regenerations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001565 Benzoates Derivatives of BENZOIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxybenzene structure. Benzoate,Benzoic Acids,Acids, Benzoic
D013764 Tetrahydronaphthalenes Partially saturated 1,2,3,4-tetrahydronaphthalene compounds. Tetralins
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D052242 Adiponectin A 30-kDa COMPLEMENT C1Q-related protein, the most abundant gene product secreted by FAT CELLS of the white ADIPOSE TISSUE. Adiponectin modulates several physiological processes, such as metabolism of GLUCOSE and FATTY ACIDS, and immune responses. Decreased plasma adiponectin levels are associated with INSULIN RESISTANCE; TYPE 2 DIABETES MELLITUS; OBESITY; and ATHEROSCLEROSIS. ACRP30 Protein,Adipocyte Complement-Related Protein 30-kDa,Adipocyte, C1q and Collagen Domain Containing Protein,Adipose Most Abundant Gene Transcript 1,apM-1 Protein,Adipocyte Complement Related Protein 30 kDa,apM 1 Protein
D018345 Mice, Knockout Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes. Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out

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