A near-infrared fluorescent probe for imaging sulfite-associated changes in experimental renal injury.

Abstract

Dissolved S(IV), present mainly as sulfite/bisulfite under near-physiological conditions, participates in sulfur metabolism and redox homeostasis, but its association with renal injury remains difficult to visualize. Here, we describe HD-ZHR, a hemicyanine-based near-infrared turn-on probe in which a levulinate masking group suppresses fluorescence until sulfite/bisulfite-triggered deprotection restores the emissive chromophore. In PBS (10 mM, pH 7.4, 1% DMSO), HD-ZHR produced an approximately 100-fold fluorescence increase at 740 nm under 670 nm excitation, showed a linear response over 0-10 μM, reached a plateau near 40 μM, and achieved a buffer-based detection limit of 0.20 μM with a response time of approximately 120 s. The probe was evaluated in cellular imaging experiments and in mouse models of cisplatin- or gentamicin-induced nephrotoxic injury, hyperuricemic nephropathy, and diabetic kidney disease. Renal-region and ex vivo kidney fluorescence differed between control and injury groups and decreased in losartan- or metformin-treated groups, with parallel group-level changes in serum creatinine and blood urea nitrogen. Because intact probe, fluorescent product, biodistribution, clearance, and tissue sulfite were not independently quantified, these signals are interpreted as sulfite-responsive fluorescence patterns associated with experimental renal injury rather than sulfite-specific in vivo quantification or kidney targeting. HD-ZHR therefore provides a preclinical optical tool for investigating disease-associated S(IV)-responsive fluorescence, while further chemical, analytical, and pharmacokinetic validation is required.