Alterations in alveolar clearance after 4-ipomeanol-induced necrosis of Clara and ciliated cells in the terminal bronchiole of the rat.
The administration of 4-ipomeanol, [0, 10 (LD), and 25 (HD) mg/kg, ip], to rats resulted in dose-dependent degeneration and necrosis of the nonciliated (Clara) and ciliated epithelial cells of the terminal bronchioles. More extensive necrosis of the terminal bronchiolar epithelium, with exposure of the basement membrane, was produced in the HD group. Repair of the terminal bronchiolar epithelium was complete within 10 days. Alveolar clearance of 51Cr labeled polystyrene latex microspheres was analyzed through 40 days postinstillation by nonlinear regression for a double exponential model. Alveolar clearance during phase 1 (Days 2 to 6) was delayed and significantly decreased in both the LD and HD groups. Alveolar clearance during phase 2 (Days 10 to 40) was significantly decreased only in the HD group. The decreased alveolar clearance in HD subjects was long term and did not correlate with the return of morphologically normal appearing Clara and ciliated cell structure.
D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D002923:Cilia / Q000473:pathology*; D006207:Half-Life; D008297:Male; D008657:Metabolic Clearance Rate; D008855:Microscopy, Electron, Scanning; D009336:Necrosis; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013729:Terpenes / Q000633:toxicity*; D013997:Time Factors
D013729:Terpenes; C001470:4-ipomeanol