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

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Abstract

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 galactosyl-hydroxylysyl 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 shortterm 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.

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Authors and Affiliations

  1. Department of Pathology, University of Oulu, Kajaanintie 52 D, FIN-90220, Oulu, Finland

    Paavo Pääkkö & Raija Sormunen

  2. Department of Internal Medicine, University of Oulu, Kajaanintie 52 D, FIN-90220, Oulu, Finland

    Lasse Ryhänen

  3. Department of Medical Biochemistry, University of Oulu, Kajaanintie 52 D, FIN-90220, Oulu, Finland

    Leena Ala-Kokko & Lasse Ryhänen

  4. Collagen Research Unit, University of Oulu, Kajaanintie 52 D, FIN-90220, Oulu, Finland

    Leena Ala-Kokko

  5. Biocenter, University of Oulu, Kajaanintie 52 D, FIN-90220, Oulu, Finland

    Leena Ala-Kokko

  6. Institute of Electron Optics, University of Oulu, Kajaanintie 52 D, FIN-90220, Oulu, Finland

    Raija Peura

  7. Institute of Occupational Health, Helsinki, Finland

    Sisko Anttila

  8. Ultrastructure Section, Pathology Branch, NHLBI, NIH, Bethesda, Maryland, USA

    Victor J. Ferrans

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  1. Paavo Pääkkö
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  2. Sisko Anttila
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  4. Leena Ala-Kokko
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  6. Victor J. Ferrans
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  7. Lasse Ryhänen
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Pääkkö, P., Anttila, S., Sormunen, R. et al. Biochemical and morphological characterization of carbon tetrachloride-induced lung fibrosis in rats. Arch Toxicol 70, 540–552 (1996). https://doi.org/10.1007/s002040050311

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  • DOI: https://doi.org/10.1007/s002040050311

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