Using cimetidine to mitigate cisplatin-induced ototoxicity

Given the well-established role of organic cation transporter 2 (OCT2) in cisplatin uptake to the inner ear cells, and the fact that cimetidine is an FDA-approved drug with well-established inhibitory activity against OCT2, we hypothesized that inhibiting OCT2-mediated cisplatin uptake with cimetidine could eliminate or alleviate cisplatin-mediated ototoxicity. Our preliminary data showed that cisplatin can reduce the viability of House Ear Institute-Organ of Corti 1 (HEI-OC1) cells in a dose-dependent manner, and cimetidine can effectively counteract this cisplatin-induced toxicity without affecting cisplatin's effect on cancer cells. Therefore, combined application of these drugs could ameliorate cisplatin ototoxicity with minimal impact on their anti-cancer effect.