Liproxstatin-1 Protects Hair Cell-Like HEI-OC1 Cells and Cochlear Hair Cells against Neomycin Ototoxicity

Abstract EN

Ferroptosis is a recently discovered iron-dependent form of oxidative programmed cell death distinct from caspase-dependent apoptosis.

In this study, we investigated the effect of ferroptosis in neomycin-induced hair cell loss by using selective ferroptosis inhibitor liproxstatin-1 (Lip-1).

Cell viability was identified by CCK8 assay.

The levels of reactive oxygen species (ROS) were determined by DCFH-DA and cellROX green staining.

The mitochondrial membrane potential (ΔΨm) was evaluated by TMRM staining.

Intracellular iron and lipid peroxides were detected with Mito-FerroGreen and Liperfluo probes.

We found that ferroptosis can be induced in both HEI-OC1 cells and neonatal mouse cochlear explants, as evidenced by Mito-FerroGreen and Liperfluo staining.

Further experiments showed that pretreatment with Lip-1 significantly alleviated neomycin-induced increased ROS generation and disruption in ΔΨm in the HEI-OC1 cells.

In parallel, Lip-1 significantly attenuated neomycin-induced hair cell damage in neonatal mouse cochlear explants.

Collectively, these results suggest a novel mechanism for neomycin-induced ototoxicity and suggest that ferroptosis inhibition may be a new clinical intervention to prevent hearing loss.