Liproxstatin-1 Protects Hair Cell-Like HEI-OC1 Cells and Cochlear Hair Cells against Neomycin Ototoxicity
Open Access
- 1 December 2020
- journal article
- research article
- Published by Hindawi Limited in Oxidative Medicine and Cellular Longevity
- Vol. 2020, 1-15
- https://doi.org/10.1155/2020/1782659
Abstract
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 () 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 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.Keywords
Funding Information
- Sanming Project of Medicine in Shenzhen (SZSM201612031, JCYJ20180508152528735, ZDSYS201707281114196, JCYJ20170413162242627, 2019A1515011495, 19QA1401800, 81800912, 81970875, 81870728)
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