Reactive oxygen species are important mediators that exert a toxic effect during
ischemia-reperfusion injury of various organs.
Sulforaphane, which is a naturally occurring
isothiocyanate that is present in cruciferous vegetables such as broccoli, is known to be an indirect
antioxidant that acts by inducing Nrf2-dependent phase 2
enzymes. Phase 2
enzymes such as
heme oxygenase-1,
NAD(P)H:
quinone oxidoreductase 1,
glutathione reductase, and
glutathione peroxidase participate in adaptive and protective responses to oxidative stress and various inflammatory stimuli. Therefore, we evaluated the preactivation of Nrf2 by
sulforaphane to determine if it could inhibit
ischemia-reperfusion-induced kidney damage. Treatment of HK2 renal tubular epithelial cells with
sulforaphane effectively protected cells against cytotoxicity induced by
hypoxia-reoxygenation, and
sulforaphane dramatically induced phase 2
enzymes by decreasing the
Keap1 protein levels and increasing Nrf2 nuclear translocation. Additionally, a second set of experiments using a renal
ischemia-reperfusion model produced results that were essentially the same as those observed when HK2 cells were used; namely, that
sulforaphane induced Nrf2-dependent phase 2
enzymes and thereby improved
ischemia-reperfusion-induced changes in the
lipid hydroperoxides,
glutathione,
creatinine clearance, kidney weight, and histologic abnormalities. Collectively, these results suggest that
sulforaphane can be used as an effective adjunct for the prevention of renal oxidative insults during
ischemia-reperfusion injury.