Rapamycin alleviates cisplatin-induced ototoxicity in vivo

• Rapamycin treatment improved hearing status in cisplatin challenged rats.
• Rapamycin treatment decreased oxidative stress in cisplatin challenged rats.
• Rapamycin treatment preserved hair cell damages in cisplatin challenged rats.
• Rapamycin treatment promoted expression of autophagy related proteins LC3-II and Beclin-1.
• We report that rapamycin treatment attenuated cisplatin-induced ototoxicity in rat models.

BackgroundCisplatin-induced ototoxicity affects a high percentage of new cancer patients worldwide. The detailed mechanism of cisplatin-induced ototoxicity is not completely understood. We investigated whether rapamycin could protect rats from cisplatin-induced ototoxicity.MethodsForty-eight male Wistar rats were randomly divided into six groups. Three groups were intraperitoneally (IP) infused with cisplatin at a dose of 16 mg/kg and immediately injected with either dimethylsulfoxide (DMSO), rapamycin, or chloroquine (CQ). The remaining three groups were treated with rapamycin, CQ, or saline alone. The auditory brainstem response (ABR) test was performed to detect the rats’ hearing status. Serum was isolated to measure the level of the oxidative marker malondialdehyde (MDA), the basilar membrane was prepared to count the outer hair cell loss, and soft tissue samples extracted from the cochleae were lysed to analyze the microtubule-associated protein light chain 3 (LC3) and Beclin-1.ResultsThe rapamycin treatment significantly attenuated cisplatin-induced hearing loss, decreased oxidative stress, and alleviated the hair cell damage that was associated with the upregulation of the LC3-II/GAPDH ratio and increased Beclin-1 expression.ConclusionOur results demonstrated that rapamycin has an otoprotective effect; it attenuates cisplatin-induced ototoxicity, probably by attenuating oxidative damage and inducing autophagy.