Sulforaphane protects against cisplatin-induced nephrotoxicity

Toxicol Lett. 2010 Feb 15;192(3):278-85. doi: 10.1016/j.toxlet.2009.11.007. Epub 2009 Nov 12.


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 on the CDDP-induced nephrotoxicity. Preincubation of LLC-PK1 cells with 0.5-5 microM 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 microg/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Antineoplastic Agents / adverse effects*
  • Cell Death / drug effects
  • Cell Nucleus / metabolism
  • Cell Survival / drug effects
  • Cisplatin / adverse effects*
  • Dose-Response Relationship, Drug
  • Isothiocyanates
  • Kidney / cytology
  • Kidney / drug effects*
  • LLC-PK1 Cells
  • Male
  • NF-E2-Related Factor 2 / drug effects
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Sulfoxides
  • Swine
  • Thiocyanates / pharmacology*


  • Anticarcinogenic Agents
  • Antineoplastic Agents
  • Isothiocyanates
  • NF-E2-Related Factor 2
  • Sulfoxides
  • Thiocyanates
  • sulforaphane
  • Cisplatin