Induction of cell death by sodium hexachloroplatinate (IV) in the HEI-OC1 cell line, primary rat spiral ganglion cells and rat organ of Corti explants

by Elisabeth Berger, Gudrun Brandes, Odett Kaiser, Janin Reifenrath, Thomas Lenarz, Kirsten Wissel, Martin Durisin

Although cochlear implants have become a well-established method for patients with sensory neural hearing loss, clinical results indicate that in some cases, corrosion of electrode contacts leads to high impedance that interferes with successful stimulation of the auditory nerve. As it is unclear whether corrosion products induce cell damage, we focused on cell culture models of the organ of Corti cell line (HEI-OC1), rat spiral ganglion cells (SGC) and rat organ of Corti explant (OC_ex) cultivated from neonatal rat cochleae to characterize the cytotoxicity of sodium hexachloroplatinate (IV) (Na₂(PtCl₆)). The oxidative activity in HEI-OC1 cells decreased with increasing Na₂(PtCl₆) concentrations between 8 and 16 ng/μl, and live cell staining with Calcein acetoxymethyl/Ethidium homodimer III revealed an increasing number of cells with disrupted membranes. Ultrastructural evidence of mitophagy followed by necroptosis was detected. Additionally, exposure of the SGC to 15–35 ng/μl Na₂(PtCl₆) dose-dependently reduced neuronal survival and neuritogenesis, as determined by neurofilament antigen staining. In parallel, staining glial cells and fibroblasts with specific antibodies confirmed the dose-dependent induction of cell death by Na₂(PtCl₆). Exposure of the OC_ex to 25–45 ng/μl Na₂(PtCl₆) resulted in severe concentration-dependent hair cell loss. Our data show for the first time that Na₂(PtCl₆) induces cell death in a concentration-dependent manner in inner ear cell types and tissues.