In this study we investigated the protective effects and possible mechanisms of pirfenidone
(PF) in paraquat (PQ)-induced lung injury and fibrosis in mice. Lung injury was induced
by injection of PQ (20 mg/kg). Thereafter, mice orally received water and PF (100
and 200 mg/kg) for four weeks. After 28 days, the inflammation and fibrosis were determined
in the lungs by analysis of histopathology, bronchoalveolar lavage fluid (BALF) cell
count, lung wet/dry weight ratio, hydroxyproline content, and oxidative stress biomarkers.
Expression of several genes involved in fibrogenesis and modulation of reactive oxygen
species (ROS) production, such as TGF-β1, α-SMA, collagen Iα and IV, NOX1, NOX4, iNOS,
and GPX1 were determined using RT-qPCR. PF significantly decreased the lung fibrosis
and edema, inflammatory cells infiltration, TGF-β1 concentration, and amount of hydroxyproline
in the lung tissue. PF dose-dependently improved the expression level of the studied
genes to the near normal. Decreasing of lung lipid peroxidation and catalase activity,
and increasing of SOD activity in the treated mice were significant compared to the
control group. Pirfenidone ameliorate paraquat induced lung injury and fibrosis partly
through inhibition of inflammation and oxidative stress, and downregulation of genes
encoding for profibrotic cytokines and enzymatic systems for ROS production.