The blood pressure regulating hormones angiotensin II (AngII) and aldosterone (Ald) cause oxidative stress and oxidative DNA damage in kidney cells in vitro and in vivo. Strategies to prevent oxidative damage with antioxidants were ineffective in humans. Fortifying the intrinsic cellular antioxidative defense is a new approach to protect cells from oxidative attack.In kidney cells the effect of the three natural Nrf2 activators curcumin, methysticin and sulforaphane (Sulf) on Nrf2 activation and their impact on Ald-induced DNA damage was studied. Sulforaphane was additionally tested for its potential to prevent AngII-induced DNA damage and NF-kB activation.All Nrf2 activators were able to protect from Ald-induced DNA damage. Sulf and curcumin led to a significant activation of Nrf2, detected as translocation to the nucleus. These two substances were also able to increase the expression of Nrf2 in a positive feedback manner. Sulf also protected from damage inflicted by AngII. Besides increasing the expression of the antioxidative protein HO-1, Sulf also prevented activation of the pro-inflammatory transcription factor NF-kB.In conclusion, all Nrf2 activators efficiently protected from Ald- and AngII-induced oxidative DNA damage. The role of the anti-inflammatory effect of Sulf in the prevention of genomic damage needs further investigation.