Ma Siqing, Xu Heng, Huang Weihua, Gao Yongchao, Zhou Honghao, Li Xiong, Zhang Wei
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.
Hunan Key Laboratory of Pharmacogenetics. Institute of Clinical Pharmacology, Central South University, Changsha, China.
Front Physiol. 2021 Sep 29;12:706359. doi: 10.3389/fphys.2021.706359. eCollection 2021.
Cisplatin (CDDP) is one of the most frequently prescribed chemotherapy medications. However, its nephrotoxicity which often leads to acute kidney injury (AKI), greatly limits its clinical application. Chrysophanol (CHR), a mainly active anthraquinone ingredient, possesses various biological and pharmacological activities. In this study, we aimed to investigate the underlying protective mechanisms of CHR against CDDP-induced AKI (CDDP-AKI) using C57BL/6 mouse and human proximal tubule epithelial cells. , we found that pre-treatment with CHR greatly relieved CDDP-AKI and improved the kidney function and morphology. The mechanistic studies indicated that it might alleviate CDDP-AKI by inhibiting oxidative stress, apoptosis, and IKKβ/IκBα/p65/transcription factor nuclear kappa B (NF-κB) inflammation signaling pathway induced by CDDP. Moreover, we found that the cell viability of HK2 cells reduced by CDDP was partially rescued by CHR pre-incubation. Flow cytometry results further indicated that CHR pre-incubation suppressed CDDP induced cellular reactive oxygen species (ROS) generation and inhibited cell apoptosis in a dose-dependent manner. In summary, our results suggested that CHR might be a novel therapy for CDDP-induced AKI.
顺铂(CDDP)是最常用的化疗药物之一。然而,其肾毒性常常导致急性肾损伤(AKI),极大地限制了其临床应用。大黄酚(CHR)是一种主要的活性蒽醌成分,具有多种生物学和药理活性。在本研究中,我们旨在使用C57BL/6小鼠和人近端肾小管上皮细胞,研究CHR对顺铂诱导的急性肾损伤(CDDP-AKI)的潜在保护机制。我们发现,CHR预处理可大大减轻CDDP-AKI,并改善肾功能和形态。机制研究表明,它可能通过抑制顺铂诱导的氧化应激、细胞凋亡以及IKKβ/IκBα/p65/转录因子核因子κB(NF-κB)炎症信号通路来减轻CDDP-AKI。此外我们发现,CHR预孵育可部分挽救因顺铂而降低的HK2细胞活力。流式细胞术结果进一步表明,CHR预孵育以剂量依赖的方式抑制顺铂诱导的细胞活性氧(ROS)生成并抑制细胞凋亡。总之我们的结果表明CHR可能是治疗顺铂诱导的急性肾损伤的一种新疗法。