OxyFile #117

A new model of progressive pulmonary fibrosis in rats. 

Author:  Last JA; Gelzleichter TR; Pinkerton KE; Walker RM; 
         Witschi H 

Address: Department of Internal Medicine, School of Medicine, 
         University of California, Davis 95616-8542. 

Source:  Am Rev Respir Dis, 1993 Aug, 148:2, 487-94 


Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone 
and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after 
the initiation of exposure, animals began to demonstrate 
respiratory insufficiency and severe weight loss. About half of 
the rats died between Days 55 and 78 of exposure; no overt ill 
effects were observed in animals exposed to filtered air, to ozone 
alone, or to nitrogen dioxide. Biochemical findings in animals 
exposed to ozone and nitrogen dioxide included increased lung 
content of DNA, protein, collagen, and elastin, which was about 
300% higher than the control values. The collagen-specific 
crosslink hydroxy-pyridinium, a biomarker for mature collagen in 
the lung, was decreased by about 40%. These results are consistent 
with extensive breakdown and remodeling of the lung parenchyma and 
its associated vasculature. Histopathologic evaluation showed 
severe fibrosis, alveolar collapse, honeycombing, macrophage and 
mast cell accumulation, vascular smooth muscle hypertrophy, and 
other indications of severe progressive interstitial pulmonary 
fibrosis and end-stage lung disease. This unique animal model of 
progressive pulmonary fibrosis resembles the final stages of human 
idiopathic pulmonary fibrosis and should facilitate studying 
underlying mechanisms and potential therapy of progressive 
pulmonary fibrosis.