Ortega-Domínguez Bibiana, Aparicio-Trejo Omar Emiliano, García-Arroyo Fernando E, León-Contreras Juan Carlos, Tapia Edilia, Molina-Jijón Eduardo, Hernández-Pando Rogelio, Sánchez-Lozada Laura Gabriela, Barrera-Oviedo Diana, Pedraza-Chaverri José
Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City 04510, Mexico.
Department of Nephrology and Laboratory of Renal Pathophysiology, National Institute of Cardiology "Ignacio Chávez", Mexico City 14080, Mexico.
Food Chem Toxicol. 2017 Sep;107(Pt A):373-385. doi: 10.1016/j.fct.2017.07.018. Epub 2017 Jul 8.
Cisplatin is widely used as chemotherapeutic agent for treatment of diverse types of cancer, however, acute kidney injury (AKI) is an important side effect of this treatment. Diverse mechanisms have been involved in cisplatin-induced AKI, such as oxidative stress, apoptosis and mitochondrial damage. On the other hand, curcumin is a polyphenol extracted from the rhizome of Curcuma longa L. Previous studies have shown that curcumin protects against the cisplatin-induced AKI; however, it is unknown whether curcumin can reduce alterations in mitochondrial bioenergetics and dynamic in this model. It was found that curcumin prevents cisplatin-induced: (a) AKI and (b) alterations in the following mitochondrial parameters: bioenergetics, ultrastructure, hydrogen peroxide production and dynamic. In fact, curcumin prevented the increase of mitochondrial fission 1 protein (FIS1), the decrease of optic atrophy 1 protein (OPA1) and the decrease of NAD-dependent deacetylase sirtuin-3 (SIRT3), a mitochondrial dynamic regulator as well as the increase in the mitophagy associated proteins parkin and phosphatase and tensin homologue (PTEN)-induced putative kinase protein 1 (PINK1). In conclusion, the protective effect of curcumin in cisplatin-induced AKI was associated with the prevention of the alterations in mitochondrial bioenergetics, ultrastructure, redox balance, dynamic, and SIRT3 levels.
顺铂作为一种化疗药物被广泛用于治疗多种类型的癌症，然而，急性肾损伤（AKI）是这种治疗的一种重要副作用。顺铂诱导的急性肾损伤涉及多种机制，如氧化应激、细胞凋亡和线粒体损伤。另一方面，姜黄素是从姜黄根茎中提取的一种多酚。先前的研究表明，姜黄素可预防顺铂诱导的急性肾损伤；然而，在该模型中姜黄素是否能减少线粒体生物能量学和动力学的改变尚不清楚。研究发现，姜黄素可预防顺铂诱导的：（a）急性肾损伤和（b）以下线粒体参数的改变：生物能量学、超微结构、过氧化氢生成和动力学。事实上，姜黄素可预防线粒体分裂蛋白1（FIS1）的增加、视神经萎缩蛋白1（OPA1）的减少以及NAD依赖性脱乙酰酶sirtuin-3（SIRT3）的减少，SIRT3是一种线粒体动力学调节因子，同时还可预防与线粒体自噬相关的蛋白帕金以及磷酸酶和张力蛋白同源物（PTEN）诱导的假定激酶蛋白1（PINK1）的增加。总之，姜黄素对顺铂诱导的急性肾损伤的保护作用与预防线粒体生物能量学、超微结构、氧化还原平衡、动力学和SIRT3水平的改变有关。
