Yang Yuan, Liu Hong, Liu Fuyou, Dong Zheng
Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Arch Toxicol. 2014 Jun;88(6):1249-56. doi: 10.1007/s00204-014-1239-1. Epub 2014 May 24.
Nephrotoxicity is a major side effect of cisplatin in chemotherapy. Pathologically, cisplatin nephrotoxicity is characterized by cell injury and death in renal tubules. The research in the past decade has gained significant understanding of the cellular and molecular mechanisms of tubular cell death, revealing a central role of mitochondrial dysregulation. The pathological changes in mitochondria in cisplatin nephrotoxicity are mainly triggered by DNA damage response, pro-apoptotic protein attack, disruption of mitochondrial dynamics, and oxidative stress. As such, inhibitory strategies targeting these cytotoxic events may provide renal protection. Nonetheless, ideal approaches for renoprotection should not only protect kidneys but also enhance the anticancer efficacy of cisplatin in chemotherapy.
肾毒性是顺铂化疗中的主要副作用。在病理上，顺铂肾毒性的特征是肾小管中的细胞损伤和死亡。过去十年的研究对肾小管细胞死亡的细胞和分子机制有了重要认识，揭示了线粒体失调的核心作用。顺铂肾毒性中线粒体的病理变化主要由DNA损伤反应、促凋亡蛋白攻击、线粒体动力学破坏和氧化应激触发。因此，针对这些细胞毒性事件的抑制策略可能提供肾脏保护。尽管如此，理想的肾脏保护方法不仅应保护肾脏，还应增强顺铂在化疗中的抗癌疗效。
