Salidroside Protects Cochlear Hair Cells from Cisplatin-Induced Oxidate Stress through Activating PINK1/Parkin-Mediated Mitophagy

Background: Cisplatin (Cis) is a common chemotherapy medication which is widely applied to treat various types of tumors. But ototoxicity caused by Cis is the major concern of its application. Salidroside (Sal) is the primary active component of Rhodiola rosea, which has multiple pharmacological effects, including anti-inflammatory and antioxidant. This study was performed to evaluate the protective effect and understand the potential mechanisms of Sal on Cis-induced ototoxicity. Methods: Neonatal cochlear explants and HEI-OC1 cells were adopted to construct the Cis damage model, and treated with Sal. The effects of Sal on HEI-OC1 cells viability were detected using Cell Counting Kit-8 (CCK-8) and Adenosine Triphosphate (ATP) assay. The mitochondrial membrane potentials (MMPs) and the cellular and mitochondrial reactive oxygen species (ROS) levels in HEI-OC1 cells were evaluated. The hair cells in neonatal cochlear explants were labeled using immunofluorescence. The protein related to phosphatase and tensin homolog deleted on chromosome ten (PTEN) induced putative kinase 1 (PINK1)/Parkin pathway was detected by western blot. The neonatal cochlear explants and HEI-OC1 cells were incubated with mitochondrial division inhibitor 1 (Mdivi-1). The changes in cell viability and ROS level in HEI-OC1 cells and the number of hair cells in neonatal cochlear explants were examined. Results: Sal increased the cell viability and MMPs, and inhibited the cellular and mitochondrial ROS levels in Cis-induced HEIOC1 cells. Besides, Sal increased the number of hair cells, and enhanced the PINK1/Parkin pathway-mediated mitophagy in neonatal cochlear explants induced by Cis. Mdivi-1 reversed the protective effect of Sal on ototoxicity caused by Cis. Conclusions: Sal promotes mitochondrial autophagy by activating the PINK1/Parkin pathway. It protects hair cells from Cisinduced ototoxicity by scavenging ROS accumulation.