BIOCHEMICAL AND MORPHOLOGICAL CHARACTERIZATION OF CARBON-TETRACHLORIDE INDUCED LUNG FIBROSIS IN RATS

The short-term and long-term lung CCl4 injuries in rats were studied b y 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 fro m short-term injury; chronic interstitial pneumonia from long term inj ury, and residua of injury or advanced chronic interstitial pneumonia in the progression group. All groups also exhibited features for diffu se alveolar damage. Connective tissue stains revealed both interstitia l and intra-alveolar fibrosis in short-term injury. Hydroxyproline con tent and the activities of prolyl hydroxylase and galactosyl-hydroxyly syl glucosultransferase were elevated. This suggests an early onset of pulmonary fibrosis. Immunohistochemistry revealed the interstitial ac cumulation 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 intraalveolar fibrosis, BM proteins and type III pN- collagen, and also hydroxyproline content were greater in long-term in jury, while the progression group showed on average fewer fibrotic cha nges than did the long-term injury group, but more than the shortterm injury pointing to persistence or progression of the changes. Addition ally, intra-alveolar crystallized haemoglobin was found following shor t-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.