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

Abstract

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 (O₂˙⁻), 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 O₂˙⁻ 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 O₂˙⁻ in living cells and tissues by dual-model confocal imaging, and to trap the fluctuation of the O₂˙⁻ 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 O₂˙⁻ in complex nephrotoxicity disease systems.