论文名称：Precise Monitoring of Drug-Induced Kidney Injury Using an Endoplasmic Reticulum-Targetable Ratiometric Time-Gated Luminescence Probe for Superoxide Anions 论文类型：期刊论文 发表刊物：ANALYTICAL CHEMISTRY 收录刊物：PubMed、EI、SCIE 卷号：91 期号：21 页面范围：14019-14028 ISSN号：0003-2700 摘要：Drug-induced acute kidney injury (AKI), caused by renal drug metabolism, has been considered to be a major barrier in drug development and clinical treatment. Among various drugs, anticancer drugs, cisplatin, and aminoglycoside antibiotic gentamicin, are known to be able to induce excessive or unfolded accumulation of proteins in the endoplasmic reticulum (ER) of cells, leading to ER stress. Meanwhile, reactive oxygen species (ROS) are formed, and superoxide anion (O-2(center dot-)), the first produced ROS, is a key species to induce the AKI. Due to the lack of appropriate tools, the early diagnosis of AKI induced by cisplatin, gentamicin, or other drugs is still a crucial challenge. Herein, we report a lanthanide complex-based ER-targetable luminescence probe for O-2(center dot-), ER-(4'-trifluoromethanesulfonyloxy-2,2':6',2"-terpyridine-6,6"-diyObis(methylenenitrilo)tetrakis (aceticacid) (NETTA)-Eu3+/Tb3+, for the sensitive monitoring of drug-induced AKI via mapping the generation of O-2(center dot-) in live cells and laboratory animals. Using this probe coupled with the ratiometric time-gated luminescence (RTGL) imaging technique, the changes of O-2(center dot-) level in the ER of live cells induced by different stimuli were precisely monitored. More importantly, the substantial increases in O-2(center dot-) levels were observed in the cisplatin- and gentamicin-induced kidney injury of mice. In addition, the protective effects of L-carnitine (LC) and epigallocatechin-3-gallate (EGCG) against cisplatin- and gentamicin-induced nephrotoxicity were visualized and elucidated for the first time. The results demonstrated the potential of ER-NETTA-Eu3+/Tb3+ for examining and monitoring O-2(center dot-) in drug-induced AKI and for providing a diagnosis and treatment of nephrotoxicity diseases. 发表时间：2019-11-05
