title: Pirfenidone ameliorates concanavalin A-induced hepatitis in mice via modulation of reactive oxygen species/nuclear factor kappa B signalling pathways.
abstract: OBJECTIVE
  This study aimed to evaluate the potential protective effects of pirfenidone (PFD) against concanavalin A (Con A)-induced hepatitis in mice.
  
  
  METHODS
  Autoimmune model of hepatitis was established using single intravenous injection of Con A. Mice were randomly assigned into four groups as follows: control group; Con A group; and two groups, receiving PFD in two dose levels (200, 300 mg/kg) for 5 days before Con A administration. Extent of hepatitis was studied using biochemical, histopathological and immunohistochemical estimations.
  
  
  RESULTS
  Hepatitis was clearly evident through extensive hepatocellular lesions and elevated levels of serum transaminases, alkaline phosphatase and lactate dehydrogenase. Con A induced an imbalance between oxidant and antioxidant status in the hepatic tissue. Furthermore, Con A significantly elevated hepatic nuclear factor kappa B (NF-κB) expression and inflammatory cytokines levels (tumour necrosis factor-alpha, interleukin-6 and nitric oxide). PFD pretreatment potently ameliorated all these pathological changes.
  
  
  CONCLUSIONS
  Pirfenidone hepatoprotective activity may be mediated through its antioxidant ability that suppresses NF-κB activation signalling pathways suggesting that PFD may be a new candidate for treatment of acute hepatitis.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors.forename: Dina S
authors.initials: DS
authors.lastname: El-Agamy
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003208:Concanavalin A; D019610:Cytoprotection; D004195:Disease Models, Animal; D019693:Hepatitis, Autoimmune / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D011728:Pyridones / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D016328:NF-kappa B; D011728:Pyridones; D017382:Reactive Oxygen Species; D003208:Concanavalin A; C093844:pirfenidone
keywords: concanavalin A; hepatitis; nuclear factor kappa B; oxidative stress; pirfenidone