Salidroside Attenuates Cisplatin-Induced Ototoxicity: An Experimental Study In Vitro and In Vivo

Oxidative damage to hair cells is the major cause of ototoxicity induced by cisplatin (cis)-based chemotherapy. In this study, we aimed to assess how salidroside (SAL) protected cochlear explants (CEs) and HEI-OC1 cell lines against cis-induced ototoxicity and reduced relative hearing loss in mouse models. Furthermore, the protective mechanism of the Nrf2/ARE pathway was investigated. Cell Counting Kit-8 was used to measure the viability of HEI-OC1 cells. Flow cytometry and the TUNEL assay were used to evaluate cell apoptosis. Flow cytometry was used to measure intracellular reactive oxygen species (ROS). Immunofluorescence staining determined the changes in mitochondrial membrane potential (ΔΨm). Western blot was used to measure the levels of caspase-3 and Nrf-2. An analysis of Nrf2 and target gene levels of expression was conducted using qRT-PCR. Hearing was monitored using auditory brainstem response audiometry. In cochlear explants, SAL inhibits cis-induced apoptosis of HEI-OC1 cells and decreased hair cell apoptosis. SAL inhibited cis-induced apoptosis by lowering intracellular ROS, preserving mitochondrial function, and reducing caspase-3 expression. Moreover, auditory cells were protected from the toxic effects of cis by the Nrf2-ARE pathway after treatment with SAL. In Vivo , SAL could protect against cis-induced hearing loss, and the use of the PLGA-poloxamer nanohydrogel as a carrier increased the protection efficiency of SAL. Through its ability to reduce oxidative stress, SAL could protect auditory cell lines from cis-induced apoptosis In Vitro and attenuate cis-induced hearing loss In Vivo . Nano-based drug delivery can improve the protection efficiency of SAL. Further research should be conducted on the antioxidant capacity of SAL and its use in ototoxicity.