Objective. Systemic administration of dieckol reportedly ameliorates acute hearing loss. In this study, dieckol was delivered to the inner ear by the intratympanic route. The functional and anatomic effects and safety of dieckol were assessed using the rat ototoxicity model. Materials and methods. Dieckol in a high-molecular-weight hyaluronic acid vehicle (dieckol+vehicle group) or vehicle without dieckol (vehicle-only group) were randomly delivered into 12 ears intratympanically. Ototoxic hearing loss was induced by intravenous administration of cisplatin, gentamicin, and furosemide. The hearing threshold and surviving outer hair cells (OHC) were enumerated. Biocompatibility was assessed by serial endoscopy of the tympanic membrane (TM), and the histology of the TM and the base of bulla (BB) mucosa was quantitatively assessed. Results. The hearing threshold was significantly better (difference of 20 dB SPL) in the dieckol+vehicle group than in the vehicle-only group. The number of surviving OHCs was significantly greater in the dieckol+vehicle group than in the vehicle-only group. There were no signs of inflammation or infection in the ear. The thickness of the TM and the BB mucosa did not differ between the two groups. Conclusion. Intratympanic local delivery of dieckol may be a safe and effective method to prevent ototoxic hearing loss.

Background: Organic cation transporter 2 (OCT2) mediates the renal uptake of cisplatin and is a principal contributor to its dose-limiting nephrotoxicity. Despite reports of OCT2 inhibition by various phytochemicals, the structure–activity relationships (SARs) governing inhibition and their functional implications remain poorly understood. Methods: We systematically evaluated OCT2 inhibitory activity across a structurally diverse library of 146 phytochemicals, including anthraquinones, flavanols, stilbenes, and isoflavones, using Madin–Darby canine kidney (MDCK) cells stably overexpressing OCT2. Structure–activity relationships were analyzed using non-parametric statistics and multivariate logistic regression, and functional relevance was assessed via cisplatin-induced cytotoxicity assays. Results: Inhibitory activity varied widely across the library, with potent inhibitors identified across multiple chemical scaffolds. Non-parametric statistical analyses revealed no significant differences in overall activity distributions among scaffold classes. Notably, chemical substituent patterns, rather than core scaffold identity, were the primary drivers of OCT2 inhibitory potency. Methoxylation was consistently associated with enhanced OCT2 inhibition, particularly within isoflavones, although its impact varied across structural scaffolds. The selected OCT2 inhibitors markedly reduced cisplatin-mediated cell death in OCT2-expressing cells but not in mock-transfected controls, confirming an OCT2-dependent mechanism of protection. Conclusions: This study establishes a structure-guided framework linking phytochemical OCT2 inhibition to nephroprotective potential and identifies methoxylation as a major determinant of OCT2-targeted intervention strategies.