Sulforaphane protects kidneys against ischemia-reperfusion injury through induction of the Nrf2-dependent phase 2 enzyme.
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.
Yoon
Ha-Yong
HY
Department of Biochemistry, Medical School and Institute for Medical Sciences, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea.
Kang
Nam-In
NI
Lee
Hern-Ku
HK
Jang
Kyu Yun
KY
Park
Jin-Woo
JW
Park
Byung-Hyun
BH
D000818:Animals; D016923:Cell Death; D002460:Cell Line; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D017879:Isothiocyanates; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000166:cytology; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000517:prevention & control*; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology* / Q000627:therapeutic use
D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane; D010100:Oxygen