Preliminary results of the inhibitory effect of Z-VAD on oxidative stress by ionic platinum in rat spiral ganglion cells.

Introduction  Previous studies of explanted cochlear implants (CI) from both animal models and CI patients demonstrate corrosion processes at platinum electrode contacts. Studies of these eroded surfaces and at the electrode-nerve interface demonstrated the release of ionic and particulate platinum. The distribution and mode of action of platinum ions on inner ear tissues have been poorly studied. Similarly, studies on the inhibition of induction of apoptotic signaling pathways in target cells of the inner ear are needed. The aim of this study is to characterize the effects of Z-VAD, a pan-caspase inhibitor of oxidative stress induced by disodium hexachloroplatinate (Na2PtCl6), and BDNF on spiral ganglion neurons (SGN) in cell culture.

Methods Spiral ganglion cells were extracted from the inner ear of neonatal rats (P3-5), separated and cultured together with 25 ng/μl Na2PtCl6 and Z-VAD (20-60 μM) and BDNF (10-50 ng/ml) for 48 h. Neurite growth and cell morpholgy of SGN were assessed by fluorescence microscopy using neurofilament antigen staining. Results: Fluorescence microscopy images showed a significantly increased number of surviving neurons and extensive neuritogenesis after incubation with BDNF compared to culture assays of SGN with Na2PtCl6 alone. In contrast, only minor improvements in SGN survival were observed after administration of Z-VAD in a dose-independent manner.

Conclusions  The potential protective effect of BDNF on neurons under oxidative stress induced by Na2PtCl6 was demonstrated even at low concentrations. In contrast, Z-VAD as a potential inhibitor of apoptosis signaling cascades did not exert the same effect. It is debatable whether Na2PtCl6 induces cell death signaling pathways other than apoptosis.

Deutsche Forschungsgemeinschaft

Publication History

Article published online:
12 May 2023