A Tumor-Bearing Mouse Model of Cisplatin-Induced Hearing Loss for Preclinical Otoprotectant Evaluation

Cisplatin is a highly efficacious chemotherapeutic agent against a variety of human cancers. However, one of its adverse effects is irreversible sensorineural hearing loss. Currently, no widely applicable clinical strategy is available to prevent cisplatin‑induced ototoxicity. Furthermore, the potential effects of many candidate otoprotective agents on cisplatin's antitumor efficacy remain poorly defined, largely due to the lack of a preclinical model capable of concurrently evaluating otoprotection and antitumor efficacy. To address this gap, we developed a novel preclinical animal model for the simultaneous assessment of otoprotective and antitumor effects. Human hepatoblastoma (HuH-6) cells were subcutaneously xenografted into nude mice, followed by administration of a clinically relevant, multi-cycle cisplatin regimen (4 mg/kg/day, 4 days on/6 days off for three cycles). Comprehensive assessment confirmed that this protocol induced significant hearing threshold elevations alongside characteristic cochlear histopathology, including hair cell loss, ribbon synapse degeneration, spiral ganglion neuron loss, and stria vascularis atrophy. The model also recapitulated systemic cisplatin toxicities-hematopoietic suppression, hepatotoxicity, and nephrotoxicity-while maintaining potent tumor growth inhibition. Thus, this model overcomes a key translational barrier by providing an integrated platform for comprehensively evaluating otoprotective compounds and identifying those that preserve hearing without compromising cisplatin's anticancer activity.