Schisandrin B protect inner hair cells from cisplatin by inhibiting celluar oxidative stress and apoptosis

Cisplatin is an effective chemotherapeutic agent; however, ototoxicity is one of its negative effects that greatly limits the use of cisplatin in clinical settings. Previous research has shown that the most important process cisplatin damage to inner ear cells, such as hair cells (HCs), is the excessive production and accumulation of ROS. Schisandrin B (SchB), is a low-toxicity, inexpensive, naturally occurring antioxidant with a variety of pharmacological effects. Therefore, the potential antioxidant effects of SchB may be useful for cisplatin ototoxicity treatment. In this study, the effects of SchB on cochlear hair cell viability, ROS levels, and expression of apoptosis-related molecules were evaluated by CCK-8, immunofluorescence, flow cytometry, and qRT-PCR, as well as auditory brainstem response (ABR) and dysmorphic product otoacoustic emission (DPOAE) tests to assess the effects on inner ear function. The results showed that SchB treatment increased cell survival, prevented Apoptosis, and reduced cisplatin-induced ROS formation. SchB treatment reduced the loss of cochlear HCs caused by cisplatin in exosome culture. In addition, SchB treatment attenuated cisplatin-induced hearing loss and HC loss in mice. This study demonstrates the ability of SchB to inhibit cochlear hair cell Apoptosis and ROS generation and shows its potential therapeutic effect on cisplatin ototoxicity.

Apoptosis; Cisplatin; Hair cell damage; Hearing loss; ROS; Schisandrin B.