A new model of progressive pulmonary fibrosis in rats

Journal Article · Sun Aug 01 04:00:00 EDT 1993 · American Review of Respiratory Disease; (United States)

DOI:https://doi.org/10.1164/ajrccm/148.2.487· OSTI ID:6121848

Last, J A; Gelzleichter, T R; Pinkerton, K E; Walker, R M; Witschi, H ^[1]

---

1. Univ. of California, Davis (United States)

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.

• OSTI ID: 6121848
• Journal Information: American Review of Respiratory Disease; (United States), Journal Name: American Review of Respiratory Disease; (United States) Vol. 148:2; ISSN ARDSBL; ISSN 0003-0805
• Country of Publication: United States
• Language: English

Related Subjects

550900 -- Pathology
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
AMINO ACIDS
ANIMALS
AZINES
AZOLES
BIOLOGICAL MODELS
BODY
CARBOXYLIC ACIDS
CHALCOGENIDES
COLLAGEN
DISEASES
DNA
ENVIRONMENTAL EXPOSURE
FIBROSIS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROXY ACIDS
HYDROXYPROLINE
HYPERTROPHY
INHALATION
INTAKE
LUNGS
MAMMALS
MORTALITY
NITROGEN COMPOUNDS
NITROGEN DIOXIDE
NITROGEN OXIDES
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXIDES
OXYGEN COMPOUNDS
OZONE
PATHOLOGICAL CHANGES
PROTEINS
PYRIDINES
PYRROLES
PYRROLIDINES
RATS
RESPIRATORY SYSTEM
RESPIRATORY SYSTEM DISEASES
RODENTS
SCLEROPROTEINS
VERTEBRATES