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Deferoxamine protects cochlear hair cells and hair cell-like HEI-OC1 cells against tert-butyl hydroperoxide-induced ototoxicity.
Lu, Pei-Heng; Ma, Peng-Wei; Wang, Wei-Long; Gao, Wei; Chen, Jia-Wei; Yuan, Hao; Ding, Xue-Rui; Lun, Yu-Qiang; Liang, Rui; Li, Si-Yu; Wang, Zi; Guo, Jia-Ning; Mei, Hong-Kai; Lu, Lian-Jun.
Afiliación
  • Lu PH; Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China.
  • Ma PW; Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China.
  • Wang WL; Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China.
  • Gao W; Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China.
  • Chen JW; Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China.
  • Yuan H; Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China.
  • Ding XR; Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China.
  • Lun YQ; Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China.
  • Liang R; Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China.
  • Li SY; Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China.
  • Wang Z; Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China.
  • Guo JN; Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China.
  • Mei HK; Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China.
  • Lu LJ; Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China. Electronic address: lulianj@fmmu.edu.cn.
Biochim Biophys Acta Mol Basis Dis ; 1870(3): 167024, 2024 03.
Article en En | MEDLINE | ID: mdl-38242180
ABSTRACT
Oxidative stress is the common mechanism of sensorineural hearing loss (SNHL) caused by many factors, such as noise, drugs and ageing. Here, we used tert-butyl hydroperoxide (t-BHP) to cause oxidative stress damage in HEI-OC1 cells and in an in vitro cochlear explant model. We observed lipid peroxidation, iron accumulation, mitochondrial shrinkage and vanishing of mitochondrial cristae, which caused hair cell ferroptosis, after t-BHP exposure. Moreover, the number of TUNEL-positive cells in cochlear explants and HEI-OC1 cells increased significantly, suggesting that t-BHP caused the apoptosis of hair cells. Administration of deferoxamine (DFOM) significantly attenuated t-BHP-induced hair cell loss and disordered hair cell arrangement in cochlear explants as well as HEI-OC1 cell death, including via apoptosis and ferroptosis. Mechanistically, we found that DFOM treatment reduced t-BHP-induced lipid peroxidation, iron accumulation and mitochondrial pathological changes in hair cells, consequently mitigating apoptosis and ferroptosis. Moreover, DFOM treatment alleviated GSH depletion caused by t-BHP and activated the Nrf2 signalling pathway to exert a protective effect. Furthermore, we confirmed that the protective effect of DFOM mainly depended on its ability to chelate iron by constructing Fth1 knockout (KO), TfR1 KO and Nrf2 KO HEI-OC1 cell lines using CRISPR/Cas9 technology and a Flag-Fth1 (overexpression) HEI-OC1 cell line using the FlpIn™ System. Our findings suggest that DFOM is a potential drug for SNHL treatment due to its ability to inhibit apoptosis and ferroptosis by chelating iron and scavenging reactive oxygen species (ROS).
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Deferoxamina / Ototoxicidad Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Deferoxamina / Ototoxicidad Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos