Yu Xin, Ji Xinmiao, Fan Yixiang, Yu Biao, Wang Xinyu, Feng Chuanlin, Zhang Lei, Song Chao, Zhang Xin
High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
Science Island Branch of Graduate School, University of Science and Technology of China, Hefei 230036, China.
Antioxidants (Basel). 2022 Dec 29;12(1):73. doi: 10.3390/antiox12010073.
Cisplatin is one of the most widely used anti-cancer drugs that can effectively inhibit the growth of multiple types of cancer. However, its clinical application is limited by its severe side effects, especially kidney toxicity, caused by cisplatin-induced oxidative stress, inflammation and kidney cell apoptosis. Here, we found that moderate (a few hundred mT) quasi-uniform static magnetic fields (SMFs) could inhibit cisplatin-induced renal proximal tubular cell death, especially the vertically downward direction SMF. RNA-seq experiments demonstrate that SMFs induced differential gene expressions that are closely associated with oxidative stress, apoptosis, cytokine production, transmembrane transport and DNA repair. In vivo experiments show that SMFs can reduce cisplatin-induced kidney injury in cisplatin-administrated tumor-bearing mice by reducing oxidative stress, inflammation and cell apoptosis. Furthermore, high-dose cisplatin-induced acute nephrotoxicity can be effectively alleviated by SMF treatment of as little as one day, which significantly reduced the reactive oxygen species levels in kidneys and prolonged the mice's survival. Moreover, the concentration of cisplatin in the kidney was significantly attenuated in SMF-treated mice. Therefore, our study demonstrates the effects of moderate SMFs as a novel physical method to reduce oxidative stress, and revealed their future potential to be used against cisplatin-induced kidney toxicity in cancer treatment.
顺铂是应用最广泛的抗癌药物之一,能有效抑制多种癌症的生长。然而,其临床应用受到严重副作用的限制,尤其是由顺铂诱导的氧化应激、炎症和肾细胞凋亡所导致的肾毒性。在此,我们发现中等强度(几百毫特斯拉)的准均匀静磁场(SMF)能够抑制顺铂诱导的肾近端小管细胞死亡,尤其是垂直向下方向的静磁场。RNA测序实验表明,静磁场诱导了与氧化应激、细胞凋亡、细胞因子产生、跨膜转运和DNA修复密切相关的差异基因表达。体内实验表明,静磁场可通过减轻氧化应激、炎症和细胞凋亡,降低顺铂给药的荷瘤小鼠中顺铂诱导的肾损伤。此外,仅一天的静磁场治疗就能有效缓解高剂量顺铂诱导的急性肾毒性,显著降低肾脏中的活性氧水平并延长小鼠的生存期。而且,静磁场处理的小鼠肾脏中顺铂浓度显著降低。因此,我们的研究证明了中等强度静磁场作为一种新型物理方法减轻氧化应激的作用,并揭示了其在癌症治疗中对抗顺铂诱导的肾毒性的潜在应用前景。