Visualization of oxidative injury in the mouse kidney using selective superoxide anion fluorescent probes

• Published in: Chemical science (Cambridge) Vol. 9; no. 39; pp. 7606 - 7613
• Main Authors: Lv, Yun, Dan Cheng, Dan Cheng, Dongdong Su, Dongdong Su, Chen, Mei, Yin, Bin-Cheng, Yuan, Lin, Zhang, Xiao-Bing
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 21.10.2018; Royal Society of Chemistry
• Subjects: Anions; Biomarkers; Carnitine; Chemistry; Chemistry, Multidisciplinary; Fluorescent indicators; Kidneys; Medical imaging; Metabolism; Mitochondria; Organic chemistry; Oxidation; Pharmacology; Physical Sciences; Science & Technology; Selectivity; Variations; BIOMARKERS; DRUG-INDUCED HEPATOTOXICITY; IN-VITRO; DESIGN; MITOCHONDRIA; CISPLATIN-INDUCED NEPHROTOXICITY; ENDOGENOUS SUPEROXIDE; MECHANISMS; MODEL; DERIVATIVES
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/C8SC03308K

Drug-induced acute kidney injury (AKI), caused by renal drug metabolism, has been regarded as a main problem in clinical pharmacology and practice. However, due to the lack of effective biomarkers and noninvasive real-time tools, the early diagnosis of drug-induced AKI is still a crucial challenge. The superoxide anion (O 2 ˙ − ), the preliminary reactive oxidative species, is closely related to drug-induced AKI. In this paper, we reported two new mitochondria-targeted fluorescent probes for investigating AKI via mapping the fluctuation of O 2 ˙ − with high sensitivity and selectivity by the combination of rational design and a probe-screening approach. Small-molecule fluorescent probes ( Naph-O2˙− and NIR-O2˙− ) with high accuracy and excellent selectivity were successfully applied to detect endogenously produced O 2 ˙ − in living cells and tissues by dual-model confocal imaging, and to trap the fluctuation of the O 2 ˙ − level during the drug-induced nephrotoxicity. Moreover, probe NIR-O2˙− was also used to elucidate the protective effects of l -carnitine (LC) against drug-induced nephrotoxicity for the first time. Therefore, these probes may be potential chemical tools for exploring the roles of O 2 ˙ − in complex nephrotoxicity disease systems.