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Chrysophanol Relieves Cisplatin-Induced Nephrotoxicity via Concomitant Inhibition of Oxidative Stress, Apoptosis, and Inflammation.

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机构： [1]Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China, [2]Hunan Key Laboratory of Pharmacogenetics. Institute of Clinical Pharmacology, Central South University, Changsha, China, [3]Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China, [4]National Clinical Research Center for Geriatric Disorders, Changsha, China, [5]Department of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China, [6]The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong, China

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关键词： chrysophanol cisplatin acute kidney injury oxidative stress apoptosis inflammation

摘要：

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. In vivo, 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.Copyright © 2021 Ma, Xu, Huang, Gao, Zhou, Li and Zhang.

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出版当年[2021]版：

大类 | 2 区

医学

小类 | 2 区生理学

最新[2023]版：

大类 | 3 区医学

小类 | 3 区生理学

第一作者：

第一作者机构： [1]Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China, [2]Hunan Key Laboratory of Pharmacogenetics. Institute of Clinical Pharmacology, Central South University, Changsha, China, [3]Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China, [4]National Clinical Research Center for Geriatric Disorders, Changsha, China,

通讯作者：

通讯机构： [1]Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China, [2]Hunan Key Laboratory of Pharmacogenetics. Institute of Clinical Pharmacology, Central South University, Changsha, China, [3]Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China, [4]National Clinical Research Center for Geriatric Disorders, Changsha, China,

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Chrysophanol Relieves Cisplatin-Induced Nephrotoxicity via Concomitant Inhibition of Oxidative Stress, Apoptosis, and Inflammation.

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