Sulforaphane protects against cisplatin-induced nephrotoxicity

Cisplatin (cis-diamminedichloroplatinum II, CDDP) is a chemotherapeutic agent that induces nephrotoxicity associated with oxidative/nitrosative stress Sulforaphane (SFN) is an isothiocyanate produced by the enzymatic action of myrosinase on glucorophanin, a glucosinolate contained in cruciferous vegetables SFN is able to induce cytoprotective enzymes through the transcription factor Nrf2 The purpose of this study was to evaluate whether SFN induces a cytoprotective effect oil the CDDP-induced nephrotoxicity. Preincubation of LLC-PK1 cells with 0 5-5 mu M SFN by 24 h was able to prevent, in a concentration-dependent way, CDDP-induced cell death. Immunofluorescent staining confirmed the nuclear translocation of Nrf2 after treatment with SFN In the in vivo studies, CDDP was given to Wistar rats as a sole i p. injection at a dose of 7 5 mg/kg SFN (500 mu g/kg i v) was given two times (24 h before and 24 after CDDP-injection). Animals were killed three days after CDDP-injection. SFN attenuated CDDP-induced renal dysfunction, structural damage, oxidative/nitrosative stress, glutathione depletion, enhanced urinary hydrogen peroxide excretion and the decrease in antioxidant enzymes (catalase, glutathione peroxidase and glutathione-S-transferase) The renoprotective effect of SFN on CDDP-induced nephrotoxicity was associated with the attenuation in oxidative/nitrosative stress and the preservation of antioxidant enzymes. (C) 2009 Elsevier Ireland Ltd All rights reserved.