Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Edificio F, Mexico City, Mexico.
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.
顺铂（顺式二氨二氯铂 II，CDDP）是一种化疗药物，可引起与氧化/硝化应激相关的肾毒性。萝卜硫素（SFN）是一种异硫氰酸盐，由芥子酶对存在于十字花科蔬菜中的葡萄糖硫苷酶解产生。SFN 能够通过转录因子 Nrf2 诱导细胞保护酶。本研究的目的是评估 SFN 是否对 CDDP 诱导的肾毒性具有细胞保护作用。用 0.5-5 μM SFN 预孵育 LLC-PK1 细胞 24 h 可浓度依赖性地预防 CDDP 诱导的细胞死亡。免疫荧光染色证实 SFN 处理后 Nrf2 的核易位。在体内研究中，将 CDDP 作为单次腹腔注射以 7.5 mg/kg 的剂量给予 Wistar 大鼠。SFN（500μg/kg 静脉内）给药两次（CDDP 注射前 24 小时和后 24 小时）。在 CDDP 注射后三天处死动物。SFN 减轻了 CDDP 诱导的肾功能障碍、结构损伤、氧化/硝化应激、谷胱甘肽耗竭、尿过氧化氢排泄增加以及抗氧化酶（过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽-S-转移酶）减少。SFN 对 CDDP 诱导的肾毒性的肾保护作用与氧化/硝化应激的减轻和抗氧化酶的保存有关。
