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 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.
Guerrero-Beltrán
Carlos Enrique
CE
Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Edificio F, Mexico City, Mexico.
Calderón-Oliver
Mariel
M
Tapia
Edilia
E
Medina-Campos
Omar N
ON
Sánchez-González
Dolores Javier
DJ
Martínez-Martínez
Claudia María
CM
Ortiz-Vega
Karla Mariana
KM
Franco
Martha
M
Pedraza-Chaverri
José
J
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*
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane; D002945:Cisplatin