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Pirfenidone Protects Against Paraquat-Induced Lung Injury and Fibrosis in Mice by Modulation of Inflammation, Oxidative Stress, and Gene Expression Publisher Pubmed



Pourgholamhossein F1, 2 ; Rasooli R2, 3 ; Pournamdari M3 ; Pourgholi L2 ; Samarehfekri M4 ; Ghazikhansari M5 ; Iranpour M6 ; Poursalehi HR4 ; Heidari MR2, 3 ; Mandegary A2, 4
Authors
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Authors Affiliations
  1. 1. Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
  2. 2. Department of Toxicology & Pharmacology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
  3. 3. Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
  4. 4. Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
  5. 5. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Pathology and Stem Cell Research Center, Kerman University of Medical Sciences, Kerman, Iran

Source: Food and Chemical Toxicology Published:2018


Abstract

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. © 2017