DIETARY-INTAKE OF PIRFENIDONE AMELIORATES BLEOMYCIN-INDUCED LUNG FIBROSIS IN HAMSTERS

There are no clinically efficacious drugs available for preventing the development of pulmonary fibrosis (PF). In the present study, we test ed the antifibrotic potential of pirfenidone (PD) in the bleomycin (BL ) hamster model of PF. Hamsters were intratracheally instilled with is otonic saline solution or BL (7.5 U/kg/5 ml). The animals were fed con trol diet containing 0.5% PD or the same diet without the drug 2 days before and throughout the study. The four groups were as follows: sali ne-instilled and fed the control diet (SCD); saline-instilled and fed the same diet containing PD (SPD); BL-instilled and fed the control di et (BCD); and BL-instilled and fed the same diet containing PD (BPD). The animals were killed at 21 days after intratracheal instillation an d their lungs processed for various assays. The lung hydroxyproline le vels, an index of PF, in SCD, SPD, BCD, and BPD groups were 949, 970, 1759, and 990 mu g/lung, respectively. The SOD activity and malondiald ehyde equivalent levels in the corresponding groups were 443, 524, 612 , and 499 units/lung and 56, 49, 108, and 63 nmol/lung, respectively. The lung prolyl hydroxylase activities in the SPD, BCD, and BPD groups were 87%, 147%, and 93% of the control (SCD) group (4.2 x 10(4) dpm/l ung/30 minutes), respectively. The lung myeloperoxidase activities wer e 97%, 236%, and 159% of the control group (0.73 units/lung), respecti vely. BL alone caused significant increases in all the biochemical mar kers of lung toxicity, and dietary intake of PD minimized the BL toxic ity as reflected by significant decreases in all the above markers. Hi stopathologic studies revealed that there were fewer lesions of alveol ar consolidation and fibrosis in the lungs of the BPD group than in th e BCD group. It was concluded that PD is a novel antifibrotic agent an d is potentially useful in preventing the development of PF.