title: Tetomilast attenuates elastase-induced pulmonary emphysema through inhibition of oxidative stress in rabbits.
abstract: Tetomilast was originally identified as a potent inhibitor of superoxide production in human neutrophils, and is of interest because it may relieve oxidative stress related to chronic obstructive pulmonary disease (COPD). Our objective was to determine whether tetomilast effectively protects against the development of porcine pancreatic elastase (PPE)-induced emphysema in rabbits. Rabbits were divided into three groups (sham n=19, PPE n=19, PPE/Tetomilast n=18). The rabbits were once daily orally administered vehicle solution or tetomilast 5 d/week for 4 weeks before the PPE instillation. We compared pulmonary function, inflammatory cell infiltration, oxidative stress, and the incidences of apoptosis among the three groups. Tetomilast suppressed PPE-induced increases in the incidence of apoptosis and the production of 8-hydroxy-deoxyguanosine (8-OHdG) in lung tissues. PPE-instilled rabbits treated with tetomilast showed significantly less mean linear intercept and significantly better pulmonary function than rabbits administered PPE alone. Tetomilast may inhibit the development of emphysema by attenuating pulmonary inflammation and apoptosis caused by PPE-induced oxidative stress.
authors.affiliation: Second Department of Internal Medicine, Graduate School of Medicine, Gifu University, Japan.
authors.forename: Bulin
authors.initials: B
authors.lastname: Baila
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ohno
authors.forename: Hisashi
authors.initials: H
authors.lastname: Nagamoto
authors.forename: Kounori
authors.initials: K
authors.lastname: Kotosai
authors.forename: Youichi
authors.initials: Y
authors.lastname: Yabuuchi
authors.forename: Norihiko
authors.initials: N
authors.lastname: Funaguchi
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Ito
authors.forename: Junki
authors.initials: J
authors.lastname: Endo
authors.forename: Hidenori
authors.initials: H
authors.lastname: Mori
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.forename: Takako
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010196:Pancreatic Elastase; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D011817:Rabbits; D013844:Thiazoles / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D013844:Thiazoles; D010196:Pancreatic Elastase; C108965:tetomilast