**6.3 Activation of the Nrf2/ARE pathway by oxidative stress**

The induction of several cytoprotective enzymes in response to reactive chemical entities or oxidative stress is regulated at the transcriptional level via activation of Nrf2. This transcriptional response is mediated by the ARE, and is activated in response to H2O2 (Purdom-Dickinson et al., 2007) and by chemical compounds with the capacity to either undergo redox cycling or be metabolically transformed to a reactive or electrophilic intermediate (Nguyen et al., 2003). Several electrophiles, including diethyl maleate, tertbutylhydroquinone, sulforaphane (Zhang et al., 1992) and curcumin (Balogun et al., 2003) have been shown to induce Nrf2-dependent transcriptional activation of downstream target genes. In addition, several phytochemicals, such as Sulforaphane obtained from cruciferous vegetables (Zhang et al., 1992), Resveratrol (Kode et al., 2008), and Celastrol from the medicinal plant Tripterygium wilfordii (Seo et al.) have also been shown to activate the antioxidant response element . Chemical compounds such as the isothiocyanates and diethyl maleate can directly react with sulfhydryl groups and do not require metabolism. They can mimic an oxidative insult by oxidizing cysteine residues and depleting reduced cellular glutathione (GSH). Elevated levels of reactive oxygen and other electrophilic species followed by a reduced antioxidant capacity can lead to the alteration of the cellular redox status and trigger the transcriptional response mediated by Nrf2/ARE (Nguyen et al., 2009).
