Leonurine protects against cisplatin-induced ototoxicity through its anti-oxidation and anti-apoptosis properties

Cisplatin has a high efficacy for treating solid tumors, but it is generally accompanied by ototoxic side effects. Leonurine (LEO) has anti-oxidative and anti-apoptotic effects, although its role in the treatment of cisplatin-induced hearing impairment (CIHI) remains unclear. Here, we explored in vitro and in vivo models of cisplatin injury and analyzed the efficacy of LEO on cisplatin-induced ototoxicity by immunofluorescence, otoacoustic assessment, qRT-PCR, and Western blot. At the cellular level, LEO reduced oxidative stress and apoptosis, while at the organism level LEO protected guinea pigs against CIHI and maintained the hearing thresholds of cisplatin-treated guinea pigs at 50-55 dB. LEO effectively prevented cisplatin-induced decreases in hair cells, supporting cells, spiral ganglion neurons and ribbon synapses; reduced Cleaved Caspase 3 expression through activation of Bcl-2 and reducing reactive oxygen species (ROS) accumulation and improving mitochondrial membrane potential and reduced cisplatin-induced apoptosis by increasing the expression of Nrf2/Nqo1. In conclusion, the present study expands the application range of LEO and suggests that LEO is a potential therapeutic agent for preventing cisplatin ototoxicity.