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Indexed by:Journal Papers

Date of Publication:2019-11-05

Journal:ANALYTICAL CHEMISTRY

Included Journals:PubMed、EI、SCIE

Volume:91

Issue:21

Page Number:14019-14028

ISSN No.:0003-2700

Abstract: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.