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

abstract

  • 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%2b. Cells were treated with 5mM ALA and 8h later exposed to 50μM As3%2b for 24h, analyzing MTT-activity, glutathione content, Nrf2 induction and antioxidant gene expression. As3%2b increased glutathione (154%25), 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%2b exposure (from 35- to 5-times of control cells), which correlated with the reduction of Nrf2 observed in As3%2b group. ALA pretreatment can down-modulate the response mediated by Nrf2 and provide protection to As3%2b exposed HepG2 cells. © 2010 Elsevier B.V.

publication date

  • 2010-01-01