TY - JOUR
T1 - Sulforaphane protects against cisplatin-induced nephrotoxicity
AU - Guerrero-Beltrán, Carlos Enrique
AU - Calderón-Oliver, Mariel
AU - Tapia, Edilia
AU - Medina-Campos, Omar N.
AU - Sánchez-González, Dolores Javier
AU - Martínez-Martínez, Claudia María
AU - Ortiz-Vega, Karla Mariana
AU - Franco, Martha
AU - Pedraza-Chaverri, José
N1 - Funding Information:
This work was supported by DGAPA IN207007 and IN201910 and by CONACYT 89641. We thank Arturo Ruiz-García for his support with some analytical determinations. We also thank Dr. Ismael Torres-Saldaña and Dr. Enrique Pinzón-Estrada (Facultad de Medicina, UNAM) for their continuous support with the experimental animals.
PY - 2010/2/15
Y1 - 2010/2/15
N2 - 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 μM 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 μg/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.
AB - 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 μM 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 μg/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.
KW - Cisplatin
KW - Nephrotoxicity
KW - Nrf2
KW - Oxidative/nitrosative stress
KW - Renoprotection
KW - Sulforaphane
UR - http://www.scopus.com/inward/record.url?scp=75349110758&partnerID=8YFLogxK
U2 - 10.1016/j.toxlet.2009.11.007
DO - 10.1016/j.toxlet.2009.11.007
M3 - Artículo
C2 - 19913604
SN - 0378-4274
VL - 192
SP - 278
EP - 285
JO - Toxicology Letters
JF - Toxicology Letters
IS - 3
ER -