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Can Retinoic Acid Ameliorate the Physiologic and Morphologic Effects of Elastase Instillation in the Rat?
Section snippets
Materials and Methods
Adult male Sprague-Dawley rats (90 days old at the start of the experiment) received either saline solution or 1,000 IU porcine elastase on days 0 and 14. The saline solution or elastase was delivered intratracheally using a microspray device (Penn Century; Philadelphia, PA) with a mean particle size of 15 to 20 μm. Nine weeks after the first instillation, the rats were treated either with all-trans-RA (500 μg/kg, intraperitoneally, daily for 2 weeks) in tetraglycol vehicle or with vehicle
Results
No significant effect on body weight was observed among groups throughout the 11-week study. During that period, the elastase-instilled rats always showed a larger pause than the saline solution-instilled mice, suggesting that the elastase-instilled rats had airflow obstruction. After 2 weeks of RA treatment, the rats treated with elastase plus vehicle showed significant progression of the obstruction, while those treated with elastase plus RA were unchanged from their previous value (Table 1).
Conclusions
Two intratracheal instillations of elastase caused a progressive emphysema-like lesion in rats that stabilized by 9 weeks (progression data not shown). This lesion was associated with significant changes in pulmonary function similar to those observed with human emphysema (increased lung volumes and compliance, decreased forced flows and Dlco). Surprisingly, 2 weeks of treatment with RA (intraperitoneally) resulted in mild improvements in lung volumes without an effect on compliance, forced
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Cited by (0)
This research was supported by Genentech, Inc.