A light microscopic and biochemical study of carbon tetrachloride-induced pulmonary fibrosis in rats: the preventive effect of malotilate.
Orally administered malotilate was studied as a protective anti-fibrotic agent with respect to experimentally induced pulmonary fibrosis in rats. Intraperitoneally-injected carbon tetrachloride (CCI4) significantly increased the lung weight to body weight ratio, lung total protein and total hydroxyproline content, while the relative protein content of the lungs decreased. CCI4) induction caused diffuse alveolar damage and inflammatory changes mimicking usual interstitial pneumonia with interstitial fibrosis. The morphological findings suggest a primary toxic effect on the lungs. Treatment with malotilate completely normalized the lung weight to body weight ratio, lung total and relative protein content and total hydroxyproline content. Morphologically, malotilate seemed to prevent the exudative inflammatory changes and interstitial fibrosis, but not the primary toxic effect of CCI4 on the capillary endothelium or the alveolar epithelium, the result of which was diffuse alveolar damage. It is concluded that malotilate may be a useful drug for the prevention of pulmonary fibrosis.
D000818:Animals; D002251:Carbon Tetrachloride / Q000037:antagonists & inhibitors / Q000633:toxicity*; D003094:Collagen / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006909:Hydroxyproline / Q000378:metabolism; D008314:Malonates / Q000494:pharmacology*; D011658:Pulmonary Fibrosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains
D008314:Malonates; D003094:Collagen; D002251:Carbon Tetrachloride; D006909:Hydroxyproline; C024808:diisopropyl 1,3-dithiol-2-ylidenemalonate