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 tested the antifibrotic potential of pirfenidone (PD) in the bleomycin (BL) hamster model of PF. Hamsters were intratracheally instilled with isotonic saline solution or BL (7.5 U/kg/5 ml). The animals were fed control 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: saline-instilled and fed the control diet (SCD); saline-instilled and fed the same diet containing PD (SPD); BL-instilled and fed the control diet (BCD); and BL-instilled and fed the same diet containing PD (BPD). The animals were killed at 21 days after intratracheal instillation and their lungs processed for various assays. The lung hydroxyproline levels, an index of PF, in SCD, SPD, BCD, and BPD groups were 949, 970, 1759, and 990 micrograms/lung, respectively. The SOD activity and malondialdehyde 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/lung/30 minutes), respectively. The lung myeloperoxidase activities were 97%, 236%, and 159% of the control group (0.73 units/lung), respectively. BL alone caused significant increases in all the biochemical markers of lung toxicity, and dietary intake of PD minimized the BL toxicity as reflected by significant decreases in all the above markers.(ABSTRACT TRUNCATED AT 250 WORDS)
Iyer
S N
SN
Department of Molecular Biosciences, University of California-Davis, USA.
Wild
J S
JS
Schiedt
M J
MJ
Hyde
D M
DM
Margolin
S B
SB
Giri
S N
SN
D000704:Analysis of Variance; D000818:Animals; D001761:Bleomycin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D006224:Cricetinae; D004032:Diet; D006909:Hydroxyproline / Q000032:analysis; D015227:Lipid Peroxidation / Q000187:drug effects*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008647:Mesocricetus; D009195:Peroxidase / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000517:prevention & control*; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
D011728:Pyridones; D001761:Bleomycin; C093844:pirfenidone; D009195:Peroxidase; D011393:Procollagen-Proline Dioxygenase; D013482:Superoxide Dismutase; D006909:Hydroxyproline