Effect of inhaled indomethacin on distilled water-induced airway epithelial cell swelling.
We evaluated the mechanism of the anti-asthmatic effect of inhaled indomethacin (Indo) by using an animal model (guinea pigs) of airway inflammation. After being exposed to either ozone or room air at identical flow rates (5 l/min) for 2 h, guinea pigs were anesthetized, tracheostomized, and lung resistance (RL) was subsequently measured. Guinea pigs inhaled either saline or Indo (1.5 mg/ml) for 1 min before undergoing an ultrasonically nebulized distilled water (UNDW) inhalation test. RL increased significantly after 10 min of UNDW inhalation in the room air and ozone groups but more so in the ozone group. This increase in RL was significantly suppressed by pretreatment with Indo. In the morphometric assessment of airway mucosa, a significant swelling of the epithelial cells after UNDW inhalation was observed in both the room air and ozone groups but especially so in the ozone group. This increase was also suppressed with Indo pretreatment. These results suggest that the increase in RL and the swelling of airway epithelial cells induced by inhaled UNDW in ozone-exposed guinea pigs was suppressed by pretreatment of inhaled Indo and that this suppression may be one of the reasons for the anti-asthmatic effect of inhaled Indo.
Mochizuki
Hiroyuki
H
Department of Pediatrics, Gunma University School of Medicine, Maebashi 371-8511, Japan. mochihi@med.gunma-u.ac.jp
Ohki
Yasushi
Y
Arakawa
Hirokazu
H
Kato
Masahiko
M
Tokuyama
Kenichi
K
Morikawa
Akihiro
A
D000280:Administration, Inhalation; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D048429:Cell Size; D004847:Epithelial Cells / Q000187:drug effects* / Q000648:ultrastructure; D006168:Guinea Pigs; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007442:Intubation, Intratracheal; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D009330:Nebulizers and Vaporizers; D009504:Neutrophils / Q000187:drug effects; D010083:Oxidants, Photochemical / Q000008:administration & dosage / Q000633:toxicity; D010126:Ozone / Q000008:administration & dosage / Q000633:toxicity; D011453:Prostaglandins / Q000096:biosynthesis; D012137:Respiratory System / Q000033:anatomy & histology / Q000187:drug effects; D014867:Water
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007473:Ion Channels; D010083:Oxidants, Photochemical; D011453:Prostaglandins; D014867:Water; D010126:Ozone; D007213:Indomethacin