Tetomilast Attenuates Elastase-Induced Pulmonary Emphysema through Inhibition of Oxidative Stress in Rabbits

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...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2012/04/01, Vol.35(4), pp.494-502
Main Authors: Baila, Bulin, Ohno, Yasushi, Nagamoto, Hisashi, Kotosai, Kounori, Yabuuchi, Youichi, Funaguchi, Norihiko, Ito, Fumitaka, Endo, Junki, Mori, Hidenori, Takemura, Genzou, Fujiwara, Takako, Fujiwara, Hisayoshi, Minatoguchi, Shinya
Format: Article
Language:English
Subjects:
8-hydroxy-deoxyguanosine
Animals
Anti-Inflammatory Agents - therapeutic use
Apoptosis - drug effects
chronic obstructive pulmonary disease
Male
oxidative stress
Oxidative Stress - drug effects
Pancreatic Elastase
Pneumonia - chemically induced
Pneumonia - drug therapy
Pneumonia - pathology
Pneumonia - physiopathology
Pulmonary Emphysema - chemically induced
Pulmonary Emphysema - drug therapy
Pulmonary Emphysema - pathology
Pulmonary Emphysema - physiopathology
Rabbits
tetomilast
Thiazoles - therapeutic use
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Summary: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.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.35.494