Lung fibrosis is ameliorated by pirfenidone fed in diet after the second dose in a three-dose bleomycin-hamster model

Swarnalatha N. Iyer, S. B. Margolin, D. M. Hyde, S. N. Giri

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Interstitial lung fibrosis (ILF) is a life-threatening disease which has no known drug for prevention and cure. In the present study, we evaluated the antifibrotic potential of pirfenidone (PD) (5-methyl-1-phenyl-2-(1H)- pyridone) in a three-dose bleomycin (BL)-hamster model of lung fibrosis. Hamsters were intratracheally (IT) instilled with three consecutive doses of bleomycin sulfate (2.5 U/kg/5mL, 2.0 U/kg/5mL, 1.5 U/kg/3.75mL) or an equivalent volume of saline at weekly intervals. Hamsters were fed a diet after the second dose of BL containing 0.5% PD and hamster in the control groups were fed the same diet without the drug. The four groups were saline- instilled fed control diet (SCD); saline-instilled fed the same diet containing PD (SPD); BL-instilled fed control diet (BCD); and BL-instilled fed the diet containing PD (BPD). Hamsters were sacrificed at 28 days after IT instillation of last dose of saline or BL and their lungs processed for various assays. Lung hydroxyproline, an index of fibrosis, in SCD, SPD, BCD and BPD were 830, 804, 1609, 1235 μg/lung; respectively. Lung prolyl hydroxylase activities in the SPD, BCD and BPD groups were 103%, 313%, 157% of the control SCD group (5.99 x 104 dpm/lung/30 min) respectively. Malondialdehyde equivalent levels and superoxide dismutase activity in the corresponding groups were 99, 79, 240 and 145 nmoles/lung and 412, 433, 538 and 410 units/lung respectively. Lung myeloperoxidase activities in the corresponding groups were 56%, 179%, and 116% of the control group (0.44 units/lung). It is concluded that PD is a novel antifibrotic drug that has therapeutic potential in arresting the progression of an ongoing fibrotic process in the lung.

Original languageEnglish (US)
Pages (from-to)119-132
Number of pages14
JournalExperimental Lung Research
Volume24
Issue number1
StatePublished - 1998

Fingerprint

Bleomycin
Nutrition
Cricetinae
Fibrosis
Diet
Lung
Pharmaceutical Preparations
Prolyl Hydroxylases
Control Groups
pirfenidone
Hydroxyproline
Malondialdehyde
Peroxidase
Superoxide Dismutase
Assays

Keywords

  • Bleomycin
  • Hamster
  • Lung fibrosis
  • Pirfenidone

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Lung fibrosis is ameliorated by pirfenidone fed in diet after the second dose in a three-dose bleomycin-hamster model. / Iyer, Swarnalatha N.; Margolin, S. B.; Hyde, D. M.; Giri, S. N.

In: Experimental Lung Research, Vol. 24, No. 1, 1998, p. 119-132.

Research output: Contribution to journalArticle

Iyer, Swarnalatha N. ; Margolin, S. B. ; Hyde, D. M. ; Giri, S. N. / Lung fibrosis is ameliorated by pirfenidone fed in diet after the second dose in a three-dose bleomycin-hamster model. In: Experimental Lung Research. 1998 ; Vol. 24, No. 1. pp. 119-132.
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AB - Interstitial lung fibrosis (ILF) is a life-threatening disease which has no known drug for prevention and cure. In the present study, we evaluated the antifibrotic potential of pirfenidone (PD) (5-methyl-1-phenyl-2-(1H)- pyridone) in a three-dose bleomycin (BL)-hamster model of lung fibrosis. Hamsters were intratracheally (IT) instilled with three consecutive doses of bleomycin sulfate (2.5 U/kg/5mL, 2.0 U/kg/5mL, 1.5 U/kg/3.75mL) or an equivalent volume of saline at weekly intervals. Hamsters were fed a diet after the second dose of BL containing 0.5% PD and hamster in the control groups were fed the same diet without the drug. The four groups were saline- instilled fed control diet (SCD); saline-instilled fed the same diet containing PD (SPD); BL-instilled fed control diet (BCD); and BL-instilled fed the diet containing PD (BPD). Hamsters were sacrificed at 28 days after IT instillation of last dose of saline or BL and their lungs processed for various assays. Lung hydroxyproline, an index of fibrosis, in SCD, SPD, BCD and BPD were 830, 804, 1609, 1235 μg/lung; respectively. Lung prolyl hydroxylase activities in the SPD, BCD and BPD groups were 103%, 313%, 157% of the control SCD group (5.99 x 104 dpm/lung/30 min) respectively. Malondialdehyde equivalent levels and superoxide dismutase activity in the corresponding groups were 99, 79, 240 and 145 nmoles/lung and 412, 433, 538 and 410 units/lung respectively. Lung myeloperoxidase activities in the corresponding groups were 56%, 179%, and 116% of the control group (0.44 units/lung). It is concluded that PD is a novel antifibrotic drug that has therapeutic potential in arresting the progression of an ongoing fibrotic process in the lung.

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