Alpha-lipoic acid regulates heme oxygenase gene expression and nuclear Nrf2 activation as a mechanism of protection against arsenic exposure in HepG2 cells

Oxidative stress is a known mechanism induced, among other things, by arsenic toxicity. As a response, the cell triggers the synthesis of antioxidant and stress response elements like glutathione and heme oxygenase. Alpha-lipoic acid (ALA) is a well-known antioxidant that confers protection to oxidative stress conditions. We analyzed the effect of ALA pretreatment on Nrf2-responsive gene expression of HepG2 cells exposed to As3+. Cells were treated with 5mM ALA and 8h later exposed to 50μM As3+ for 24h, analyzing MTT-activity, glutathione content, Nrf2 induction and antioxidant gene expression. As3+ increased glutathione (154%), heme oxygenase, glutamate cystein ligase, modifier subunit and metallothionein (35-fold, 10-fold and 9-fold, respectively). ALA prevented the strong expression of heme oxygenase by As3+ exposure (from 35- to 5-times of control cells), which correlated with the reduction of Nrf2 observed in As3+ group. ALA pretreatment can down-modulate the response mediated by Nrf2 and provide protection to As3+ exposed HepG2 cells. © 2010 Elsevier B.V