BLEOMYCIN-INDUCED PULMONARY FIBROSIS IN THE RAT - PREVENTION WITH AN INHIBITOR OF COLLAGEN-SYNTHESIS
- 1 January 1980
- journal article
- research article
- Vol. 96 (6), 954-964
Abstract
Pharmacologic treatment of pulmonary fibrosis is limited to the use of corticosteroids occasionally combined with other immunosuppressive agents. The ability of a proline analog that is a potent inhibitor of collagen biosynthesis to prevent the manifestations of bleomycin-induced pulmonary fibrosis was tested in an animal model. Bleomycin sulfate was administered by intratracheal instillation to produce pulmonary fibrosis in male Fischer 344 rats. After 28 days lungs from bleomycin-treated animals had histologic, biochemical and functional alterations consistent with pulmonary fibrosis. Vital capacity and compliance were reduced to 62 and 41% of their respective control values. Lung prolyl hydroxylase activity doubled during the 1st wk after bleomycin, at a time when total lung collagen content remained unchanged. Thereafter, total lung collagen content slowly rose to 72% above control values at 28 days. The proline analog DHP [L-3,4-dehydroproline] was administered at a dose that completely inhibited the elevated levels of lung prolyl hydroxylase activity. Pulmonary collagen content of animals treated with DHP was only minimally elevated, and functional abnormalities were reduced. Pulmonary compliance increased significantly from 0.25-0.44 ml/cm H2O, and vital capacity increased from 3.94-5.65 ml. Proline analogs offer potential for modifying the manifestations of pulmonary fibrosis that occur as a consequence of acute lung toxic injury. Elevation of lung prolyl hydroxylase activity is an early event that serves as a useful index of the acute lung injury produced by bleomycin.This publication has 18 references indexed in Scilit:
- Pulmonary Toxicity Associated with Bischloroethylnitrosourea (BCNU)Annals of Internal Medicine, 1979
- CHRONIC INTERSTITIAL PULMONARY FIBROSIS PRODUCED IN HAMSTERS BY ENDOTRACHEAL BLEOMYCIN - LUNG-VOLUMES, VOLUME-PRESSURE RELATIONS, CARBON-MONOXIDE UPTAKE, AND ARTERIAL BLOOD-GAS STUDIESPublished by Elsevier ,1978
- Inhibition of tropoelastin secretion by incorporation of dl-3,4-dehydroprolineArchives of Biochemistry and Biophysics, 1977
- Studies on the effect of 3,4-dehydroproline on collagen metabolism in carbon tetrachloride-induced hepatic fibrosisArchives of Biochemistry and Biophysics, 1977
- EFFECT OF PARAQUAT ON RAT LUNG PROLYL HYDROXYLASE1977
- The in vivo inhibition of collagen synthesis and the reduction of prolyl hydroxylase activity by 3,4-dehydroprolineArchives of Biochemistry and Biophysics, 1976
- Respiratory mechanics in normal hamstersJournal of Applied Physiology, 1976
- Studies on the effect of l-3,4-dehydroproline on collagen synthesis by chick embryo polysemesArchives of Biochemistry and Biophysics, 1976
- Bleomycin, an Antitumor AntibioticAnnals of Internal Medicine, 1972
- A rapid assay for collagen proline hydroxylaseAnalytical Biochemistry, 1966