Effects of the Clara cell toxin, 4-ipomeanol, on pulmonary function in rats.

The naturally occurring compound, 4-ipomeanol (IPO, 1-[3-furyl]-4-hydroxy-1-pentanone), selectively damages the nonciliated epithelial (Clara) cells of the terminal bronchioles. Because information is not available concerning functional changes in IPO-treated lungs, an investigation was undertaken to evaluate the in vivo pulmonary ventilatory, mechanical, and gas exchange functions of female Long-Evans rats 24 h after treatment with a single intraperitoneal dose of 1 or 5 mg IPO/kg body wt. A preliminary toxicity study established the 24-h LD50 for intraperitoneally administered IPO at 19 +/- 3 (SD) mg/kg. Significant increases in lung fluid occurred in animals treated with 15 mg IPO/kg, and histological evidence of pulmonary edema was observed in animals treated with 10 mg IPO/kg. Treatment of rats with 5 mg IPO/kg caused a significant decrease in tidal volume and a significant increase in respiratory rate and functional residual capacity-to-total lung capacity ratio (%). In rats treated with 1 mg IPO/kg, pulmonary functions were minimally affected. The functional changes observed in IPO-treated animals can be attributed to swelling and possible dysfunction of Clara cells, with subsequent alveolar interstitial edema and stimulation of juxtapulmonary capillary receptors, or to a direct effect of the toxin on respiratory control mechanisms.