title: Sulforaphane protects against cisplatin-induced nephrotoxicity.
abstract: 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.
authors.affiliation: Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Edificio F, Mexico City, Mexico.
authors.forename: Carlos Enrique
authors.initials: CE
authors.lastname: Guerrero-Beltrán
authors.forename: Mariel
authors.initials: M
authors.lastname: Calderón-Oliver
authors.forename: Edilia
authors.initials: E
authors.lastname: Tapia
authors.forename: Omar N
authors.initials: ON
authors.lastname: Medina-Campos
authors.forename: Dolores Javier
authors.initials: DJ
authors.lastname: Sánchez-González
authors.forename: Claudia María
authors.initials: CM
authors.lastname: Martínez-Martínez
authors.forename: Karla Mariana
authors.initials: KM
authors.lastname: Ortiz-Vega
authors.forename: Martha
authors.initials: M
authors.lastname: Franco
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverri
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D017879:Isothiocyanates; D007668:Kidney / Q000166:cytology / Q000187:drug effects*; D018374:LLC-PK1 Cells; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013454:Sulfoxides; D013552:Swine; D013861:Thiocyanates / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane; D002945:Cisplatin