title: Alpha-lipoic acid regulates heme oxygenase gene expression and nuclear Nrf2 activation as a mechanism of protection against arsenic exposure in HepG2 cells.
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 As(3+). Cells were treated with 5mM ALA and 8h later exposed to 50μM As(3+) for 24h, analyzing MTT-activity, glutathione content, Nrf2 induction and antioxidant gene expression. As(3+) 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 As(3+) exposure (from 35- to 5-times of control cells), which correlated with the reduction of Nrf2 observed in As(3+) group. ALA pretreatment can down-modulate the response mediated by Nrf2 and provide protection to As(3+) exposed HepG2 cells.
authors.affiliation: Doctorado en Ciencias Biomédicas Básicas, Universidad Autónoma de San Luis Potosí, Mexico; OPD Hospital Civil de Guadalajara, Mexico.
authors.forename: Selene G
authors.initials: SG
authors.lastname: Huerta-Olvera
authors.forename: José
authors.initials: J
authors.lastname: Macías-Barragán
authors.forename: Martha E
authors.initials: ME
authors.lastname: Ramos-Márquez
authors.forename: Juan
authors.initials: J
authors.lastname: Armendáriz-Borunda
authors.forename: Fernando
authors.initials: F
authors.lastname: Díaz-Barriga
authors.forename: Fernando
authors.initials: F
authors.lastname: Siller-López