Inhibition of ferroptosis protects House Ear Institute-Organ of Corti 1 cells and cochlear hair cells from cisplatin-induced ototoxicity.
J Cell Mol Med
; 24(20): 12065-12081, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32929878
ABSTRACT
Ferroptosis is a recently recognized form of non-apoptotic cell death caused by an iron-dependent accumulation of lipid hydroperoxides, which plays important roles in a wide spectrum of pathological conditions. The present study was aimed to investigate the impact of ferroptosis on cisplatin-induced sensory hair cell damage. Cell viability was determined by Cell Counting Kit-8 and lactase dehydrogenase assays. The reactive oxygen species (ROS) levels were evaluated by 2,7-Dichlorodi-hydrofluorescein diacetate (DCFH-DA) and MitoSox-Red staining. Mitochondrial membrane potential (MMP) was measured by tetramethylrhodamine methyl ester (TMRM) staining. Lipid peroxidation, intracellular and mitochondrial iron were detected by Liperfluo, C11-BODIPY581/591 , FerroOrange and Mito-FerroGreen, respectively. We found that cisplatin treatment not only markedly augmented ROS accumulation, decreased the MMP, but increased lipid peroxidation and iron accumulation in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells. Of note, treatment with the specific ferroptosis inhibitor ferrostatin-1 could effectively abrogate the cisplatin-induced toxicity and subsequent cell death. Specifically, the improvement of mitochondrial functions is important mechanisms for protective action of ferroptosis inhibitor against cisplatin-induced damages in HEI-OC1 cells. Moreover, inhibition of ferroptosis significantly protected murine cochlear hair cells against cisplatin damage. In addition, treatment murine cochlear hair cells with ferroptosis inducer, RSL3, significantly exacerbated cisplatin-induced damage, which could be alleviated by ROS inhibitor N-acetyl-L-cysteine. Collectively, our study indicated that ferroptosis inhibition could alleviate the cisplatin-induced ototoxicity via inactivation of lipid peroxide radical and improvement of mitochondrial function in hair cells.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cisplatino
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Citoproteção
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Ferroptose
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Ototoxicidade
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Células Ciliadas Auditivas
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article