Effects of alpha lipoic acid and pirfenidone on liver cells antioxidant modulation against oxidative damage

Abstract

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. To explore the association between the antifibrogenic effect and pro-antioxidant mechanisms of alpha-lipoic acid (ALA) and pirfenidone (PFD). 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). 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. Regardless of the route of action, ALA and PFD induce the biosynthesis of antioxidants mediators which is associated with modulation of fibrogenic processes.