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Title: A new model of progressive pulmonary fibrosis in rats

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.
Authors:
; ; ; ;  [1]
  1. (Univ. of California, Davis (United States))
Publication Date:
OSTI Identifier:
6121848
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Review of Respiratory Disease; (United States); Journal Volume: 148:2
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 59 BASIC BIOLOGICAL SCIENCES; LUNGS; FIBROSIS; HYPERTROPHY; NITROGEN DIOXIDE; ENVIRONMENTAL EXPOSURE; OZONE; RATS; MORTALITY; RESPIRATORY SYSTEM DISEASES; BIOLOGICAL MODELS; COLLAGEN; DNA; HYDROXYPROLINE; INHALATION; PROTEINS; PYRIDINES; AMINES; AMINO ACIDS; ANIMALS; AZINES; AZOLES; BODY; CARBOXYLIC ACIDS; CHALCOGENIDES; DISEASES; HETEROCYCLIC ACIDS; HETEROCYCLIC COMPOUNDS; HYDROXY ACIDS; INTAKE; MAMMALS; NITROGEN COMPOUNDS; NITROGEN OXIDES; NUCLEIC ACIDS; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; OXIDES; OXYGEN COMPOUNDS; PATHOLOGICAL CHANGES; PYRROLES; PYRROLIDINES; RESPIRATORY SYSTEM; RODENTS; SCLEROPROTEINS; VERTEBRATES 560300* -- Chemicals Metabolism & Toxicology; 550900 -- Pathology