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: Bulin Baila, Yasushi Ohno, Hisashi Nagamoto, Kounori Kotosai, Youichi Yabuuchi, Norihiko Funaguchi, Fumitaka Ito, Junki Endo, Hidenori Mori, Genzou Takemura, Takako Fujiwara, Hisayoshi Fujiwara, Shinya Minatoguchi
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 35 Issue 4 Pg. 494-502 ( 2012) ISSN: 1347-5215 [Electronic] Japan
• PMID: 22466552 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Thiazoles
• Pancreatic Elastase
• tetomilast

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Apoptosis (drug effects)
• Male
• Oxidative Stress (drug effects)
• Pancreatic Elastase
• Pneumonia (chemically induced, drug therapy, pathology, physiopathology)
• Pulmonary Emphysema (chemically induced, drug therapy, pathology, physiopathology)
• Rabbits
• Thiazoles (therapeutic use)