Atilano-Roque Amandla, Wen Xia, Aleksunes Lauren M, Joy Melanie S
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of Colorado, 12850 E. Montview Blvd, Aurora, CO 80045, United States.
Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, 170 Frelinghuysen Rd, Piscataway, NJ 08854, United States.
Toxicol Rep. 2016 Jan 12;3:153-159. doi: 10.1016/j.toxrep.2016.01.006. eCollection 2016.
Cisplatin is a chemotherapeutic agent used in the treatment of solid tumors, with clinical use often complicated by kidney toxicity. Nuclear factor (erythroid-derived-2)-like 2 (Nrf2) is a transcription factor involved in kidney protectant effects. The purpose of this study was to determine whether the Nrf2 activators oltipraz, sulforaphane, and oleanolic acid could protect human kidney cells against cisplatin-induced injury and to compare the protective effects between three Nrf2 activators. Human proximal tubule cells (hPTC) and human embryonic kidney 293 cells (HEK293) were exposed to cisplatin doses in the absence and presence of Nrf2 activators. Pre- and delayed-cisplatin and Nrf2 activator exposures were also assessed. Cell viability was enhanced with Nrf2 activator exposures, with differences detected between pre- and delayed-treatments. Both sulforaphane and oltipraz increased the expression of anti-oxidant genes and These findings suggest potential human kidney protective benefits of Nrf2 activators with planned exposures to cisplatin.
顺铂是一种用于治疗实体瘤的化疗药物，其临床应用常因肾毒性而变得复杂。核因子（红系衍生-2）样2（Nrf2）是一种参与肾脏保护作用的转录因子。本研究的目的是确定Nrf2激活剂奥替普拉、萝卜硫素和齐墩果酸是否能保护人肾细胞免受顺铂诱导的损伤，并比较三种Nrf2激活剂之间的保护作用。在不存在和存在Nrf2激活剂的情况下，将人近端小管细胞（hPTC）和人胚肾293细胞（HEK293）暴露于顺铂剂量下。还评估了顺铂和Nrf2激活剂的预处理和延迟暴露。Nrf2激活剂暴露可提高细胞活力，预处理和延迟处理之间存在差异。萝卜硫素和奥替普拉均增加了抗氧化基因的表达。这些发现表明，计划暴露于顺铂时，Nrf2激活剂对人肾脏具有潜在的保护作用。
