title: [Effects of alpha lipoic acid and pirfenidone on liver cells antioxidant modulation against oxidative damage].
abstract: BACKGROUND
  Liver fibrogenic processes are related to cellular redox state. Glutathione (GSH) is the major cellular antioxidant. GSH induced activation could be related to antifibrogenic effects.
  
  
  OBJECTIVE
  To explore the association between the antifibrogenic effect and pro-antioxidant mechanisms of alpha-lipoic acid (ALA) and pirfenidone (PFD).
  
  
  METHODS
  HepG2 cells and primary HSC cultures were exposed to menadione 0.1 μM (MEN) as oxidative stress inducer and treated to ALA (5 mM) or PFD (10 μM, 100 μM y 1000 μM).
  
  
  RESULTS
  In HSC, PFD decreased cell proliferation and the expression of COL1A1, TGF-β1, TIMP1, IL6, TNFα and MCP1 induced by MEN. Furthermore it was confirmed that ALA and PFD activate diverse antioxidants mediators, however MEN decreases this response. Then, MEN, ALA and PFD induce an antioxidant response, the first one as a response to injury and the latter two as pro-antioxidant inducers. Therefore, when cells are exposed to oxidative stress, endogenous systems activate a battery of mediators that increase the antioxidant potential. When these cells are treated with ALA and PFD, de novo formation of protective genes decreases since previous elicited protection induced in response to injury, enhance ALA and PFD effects.
  
  
  CONCLUSIONS
  Regardless of the route of action, ALA and PFD induce the biosynthesis of antioxidants mediators which is associated with modulation of fibrogenic processes.
authors.forename: José
authors.initials: J
authors.lastname: Macias-Barragan
authors.forename: Alessandra
authors.initials: A
authors.lastname: Caligiuri
authors.forename: Jesús
authors.initials: J
authors.lastname: García-Banuelos
authors.forename: Maurizio
authors.initials: M
authors.lastname: Parola
authors.forename: Massimo
authors.initials: M
authors.lastname: Pinzani
authors.forename: Juan
authors.initials: J
authors.lastname: Armendariz-Borunda
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D011728:Pyridones / Q000494:pharmacology*; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D011728:Pyridones; D008063:Thioctic Acid; C093844:pirfenidone