Redox Biol. 2026 Sep;95:104294. doi: 10.1016/j.redox.2026.104294. Epub 2026 Jul 10.
ABSTRACT
Renal tubular epithelial cells are highly susceptible to mitochondrial dysfunction during acute kidney injury (AKI), in which oxidative stress and microenvironmental remodeling occur before overt functional deterioration. Hydrogen peroxide (HO) is an important but nonspecific redox mediator, whereas mitochondrial viscosity provides a complementary biophysical readout associated with organelle stress, protein aggregation, membrane damage, and impaired molecular diffusion. Simultaneous imaging of mitochondrial HO and viscosity may therefore provide a dual-parameter strategy for interrogating redox-biophysical remodeling during AKI-associated tubular injury. Here, we developed a mitochondria-targeted dual-responsive fluorescent probe, PB-PB-B(OH)2, that enables single-excitation dual-channel imaging of HO-associated oxidative stress and viscosity-related microenvironmental changes. PB-PB-B(OH)2 showed HO-responsive green emission and viscosity-sensitive red emission with limited channel cross-interference under the tested conditions. In HK-2 cells exposed to TNF-α or LPS, the probe visualized concurrent increases in mitochondrial oxidative stress-associated green fluorescence and viscosity-related red fluorescence, which were attenuated by NAC or Nec-1s treatment. In an LPS-induced AKI mouse model, PB-PB-B(OH)2 enabled dynamic renal imaging of injury-stage-dependent redox and viscosity changes, which correlated with histological injury, renal function markers, and necroptosis-related signaling proteins. Therapeutic intervention with NAC or Nec-1s reduced both fluorescence signals, supporting the use of this probe for imaging-based monitoring of renal injury progression and treatment response. These results establish PB-PB-B(OH)2 as a mitochondria-targeted dual-parameter molecular imaging tool for visualizing redox-biophysical remodeling in LPS-induced AKI, rather than as a clinically validated replacement for established AKI biomarkers.
PMID:42435653 | PMC:PMC13377442 | DOI:10.1016/j.redox.2026.104294