RRC ID 74479
Author Togami K, Kanehira Y, Tada H.
Title Possible involvement of pirfenidone metabolites in the antifibrotic action of a therapy for idiopathic pulmonary fibrosis.
Journal Biol Pharm Bull
Abstract Pirfenidone (PFD) is the first and only clinically used antifibrotic drug for the treatment of idiopathic pulmonary fibrosis (IPF). This study evaluated the antifibrotic effects of two metabolites of PFD, 5-hydroxypirfenidone (PFD-OH) and 5-carboxypirfenidone (PFD-COOH), on WI-38 cells in an in vitro lung fibroblast model. The inhibitory effects of PFD-OH and PFD-COOH on transforming growth factor-β1 (TGF-β1)-induced collagen synthesis in WI-38 cells were evaluated by measuring intracellular hydroxyproline, a major component of the protein collagen. PFD-OH and PFD-COOH at 300 and 1000 µM concentrations significantly decreased the TGF-β1-induced hydroxyproline content in WI-38 cells. These results indicate that PFD-OH and PFD-COOH have antifibrotic activities, which inhibit collagen synthesis in fibroblasts. This study suggests that the concentrations of PFD and its metabolites should be considered in clinical therapy for IPF.
Volume 36(10)
Pages 1525-7
Published 2013-1-1
DOI 10.1248/bpb.b13-00452
PII DN/JST.JSTAGE/bpb/b13-00452
PMID 24088250
MeSH Anti-Inflammatory Agents, Non-Steroidal / metabolism Anti-Inflammatory Agents, Non-Steroidal / pharmacology Anti-Inflammatory Agents, Non-Steroidal / therapeutic use* Cell Line Collagen / biosynthesis* Fibroblasts / drug effects* Fibroblasts / metabolism Humans Hydroxyproline / metabolism Idiopathic Pulmonary Fibrosis / drug therapy* Idiopathic Pulmonary Fibrosis / metabolism Lung / drug effects* Lung / metabolism Lung / pathology Pyridones / metabolism Pyridones / pharmacology Pyridones / therapeutic use* Transforming Growth Factor beta1 / metabolism*
IF 1.863
Resource
Human and Animal Cells WI-38