Biochemical and morphological characterization of carbon tetrachloride-induced lung fibrosis in rats

Arch Toxicol. 1996;70(9):540-52. doi: 10.1007/s002040050311.


The short-term and long-term lung CCl4 injuries in rats were studied by i.p. CCl4 for 2 or 5 weeks, respectively, and the lung injury in the third progression group receiving i.p. CCl4 for 2 weeks followed by 3 weeks without. Acute haemorrhagic interstitial pneumonia resulted from short-term injury; chronic interstitial pneumonia from long term injury, and residua of injury or advanced chronic interstitial pneumonia in the progression group. All groups also exhibited features for diffuse alveolar damage. Connective tissue stains revealed both interstitial and intra-alveolar fibrosis in short-term injury. Hydroxyproline content and the activities of prolyl hydroxylase and galactosylhydroxylysyl glucosultransferase were elevated. This suggests an early onset of pulmonary fibrosis. Immunohistochemistry revealed the interstitial accumulation of BM proteins. In contrast, increased type III pN-collagen could also be found in the intra-alveolar spaces. The degrees of both interstitial and intra-alveolar fibrosis, BM proteins and type III pN-collagen, and also hydroxyproline content were greater in long-term injury, while the progression group showed on average fewer fibrotic changes than did the long-term injury group, but more than the short-term injury pointing to persistence or progression of the changes. Additionally, intra-alveolar crystallized haemoglobin was found following short-term injury. We conclude that CCl4-induced lung injury is an useful experimental model to study pulmonary fibrosis. The mechanism of CCl4 lung injury is not known but free radical-mediated lipid peroxidation is suggested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Tetrachloride / toxicity*
  • Convalescence
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Hydroxyproline / analysis
  • Lung / chemistry
  • Lung / enzymology
  • Lung / ultrastructure
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / metabolism*
  • Pulmonary Fibrosis / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • gamma-Glutamyltransferase / metabolism


  • Carbon Tetrachloride
  • gamma-Glutamyltransferase
  • Hydroxyproline