Prevention of bleomycin-induced pulmonary fibrosis in the hamster by cis-4-hydroxy-l-proline.

We investigated the effect of the proline analogue cis-hydroxyproline on pulmonary fibrosis produced by intratracheal administration of bleomycin in hamsters. Two groups of animals received a single dose of bleomycin; one of these groups was also injected with cis-hydroxyproline twice daily for 30 days. Control animals received intratracheal saline. Lungs were examined on day 30. In the bleomycin group, the collagen content of lungs was 131% of the control value (p less than 0.05). Administration of cis-hydroxyproline decreased collagen accumulation to 114% of the control value (p less than 0.05). Pressure-volume curves were significantly shifted downward and to the right of control in the bleomycin group; this shift was partially prevented by cis-hydroxyproline. Morphometric studies showed that alveolar walls comprised 15% of the lung parenchyma in the control group and 19% in the bleomycin group (p less than 0.05). Administration of cis-hydroxyproline significantly decreased alveolar walls to 16% of the lung parenchyma (p less than 0.05). We conclude that cis-hydroxyproline partially prevents the chemical, structural, and functional changes of bleomycin-induced pulmonary fibrosis in the hamster.