Heme Oxygenase-1 Protects Hair Cells From Gentamicin-Induced Death

Yang, Yang; Chen, Xin; Tian, Keyong; Tian, Chaoyong; Chen, Liyang; Mi, Wenjuan; Li, Qiong; Qiu, Jianhua; Ying, Lin; Zha, Dingjun

doi:10.3389/fncel.2022.783346

Cited by 8 publications

(6 citation statements)

References 45 publications

(48 reference statements)

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“…HEI-OC1, an inner ear cell line, was kindly provided by Dr. Renjie Chai at Southeast University. HEI-OC1 cells were cultured as previously described [ 29 ]. The cells were cultured in DMEM (C11995500BT, Gibco, Grand Island, NY, United States) containing 10% FBS (10,099,141, Gibco, Grand Island, NY, United States) and 1% penicillin (SV30010, HyClone, South Logan, UT, United States) in acceptable conditions (5% CO 2 , 37 °C).…”

Section: Methodsmentioning

confidence: 99%

Norepinephrine protects against cochlear outer hair cell damage and noise-induced hearing loss via α2A-adrenergic receptor

Tian,

Yang,

Wang

et al. 2024

BMC Neurosci

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Background The cochlear sympathetic system plays a key role in auditory function and susceptibility to noise-induced hearing loss (NIHL). The formation of reactive oxygen species (ROS) is a well-documented process in NIHL. In this study, we aimed at investigating the effects of a superior cervical ganglionectomy (SCGx) on NIHL in Sprague-Dawley rats. Methods We explored the effects of unilateral and bilateral Superior Cervical Ganglion (SCG) ablation in the eight-ten weeks old Sprague-Dawley rats of both sexes on NIHL. Auditory function was evaluated by auditory brainstem response (ABR) testing and Distortion product otoacoustic emissions (DPOAEs). Outer hair cells (OHCs) counts and the expression of α2A-adrenergic receptor (AR) in the rat cochlea using immunofluorescence analysis. Cells culture and treatment, CCK-8 assay, Flow cytometry staining and analysis, and western blotting were to explore the mechanisms of SCG fibers may have a protective role in NIHL. Results We found that neither bilateral nor unilateral SCGx protected the cochlea against noise exposure. In HEI-OC1 cells, H2O2-induced oxidative damage and cell death were inhibited by the application of norepinephrine (NE). NE may prevent ROS-induced oxidative stress in OHCs and NIHL through the α2A-AR. Conclusion These results demonstrated that sympathetic innervation mildly affected cochlear susceptibility to acoustic trauma by reducing oxidative damage in OHCs through the α2A-AR. NE may be a potential therapeutic strategy for NIHL prevention.

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Section: Methodsmentioning

confidence: 99%

Norepinephrine protects against cochlear outer hair cell damage and noise-induced hearing loss via α2A-adrenergic receptor

Tian,

Yang,

Wang

et al. 2024

BMC Neurosci

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“…Encouragingly, the safety and efficacy of ebselen for the prevention of noise-induced hearing loss are undergoing phase 2 clinical trials ( Kil et al, 2017 ). Moreover, other drugs have also been found to protect hair cells from aminoglycosides by intervening in the NRF2 pathway, such as apigenin ( Jia et al, 2022 ) and Heme oxygenase-1 ( Yang et al, 2022 ).…”

Section: Apoptosis Pathways In Aminoglycoside-induced Ototoxicitymentioning

confidence: 99%

Mechanisms and otoprotective strategies of programmed cell death on aminoglycoside-induced ototoxicity

Han,

Wang,

Wang

et al. 2024

Front. Cell Dev. Biol.

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Aminoglycosides are commonly used for the treatment of life-threatening bacterial infections, however, aminoglycosides may cause irreversible hearing loss with a long-term clinical therapy. The mechanism and prevention of the ototoxicity of aminoglycosides are still limited although amounts of studies explored widely. Specifically, advancements in programmed cell death (PCD) provide more new perspectives. This review summarizes the general signal pathways in programmed cell death, including apoptosis, autophagy, and ferroptosis, as well as the mechanisms of aminoglycoside-induced ototoxicity. Additionally, novel interventions, especially gene therapy strategies, are also investigated for the prevention or treatment of aminoglycoside-induced hearing loss with prospective clinical applications.

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“…CFTR was found to directly combine with Nrf2 in human primary bronchial epithelia, and a CFTR activator effectively rescued the antioxidative function of Nrf2 [ 22 ]. Enhancing Nrf2 activation robustly attenuates gentamicin-induced sensory hair cell damage and hearing loss [ 14 , 23 , 24 ]. Kelch-like ECH-associated protein 1 (Keap1) represses Nrf2 activity when Nrf2 is inactivated, whereas Nrf2 is released from Keap1-mediated inhibition once activated.…”

Section: Introductionmentioning

confidence: 99%

Ivacaftor attenuates gentamicin-induced ototoxicity through the CFTR-Nrf2-HO1/NQO1 pathway

Hu,

Wu,

Zheng

2024

Redox Report

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Objectives Gentamicin is one of the most common ototoxic drugs that can lower patients' quality of life. Oxidative stress is a key factors inducing sensory hair cell death during gentamicin administration. So far, there are no effective drugs to prevent or treat gentamicin- induced hearing loss. A recent study found cystic fibrosis transmembrane conductance regulator (CFTR) as a new target to modulate cellular oxidative balance. The objective of this study was to estimate the effect of the CFTR activator ivacaftor on gentamicin-induced ototoxicity and determine its mechanism. Methods The hair cell count was analyzed by Myosin 7a staining. Apoptosis was analyzed by TUNEL Apoptosis Kit. Cellular reactive oxygen species (ROS) level was detected by DCFH-DA probes. The Nrf2 related proteins expression levels were analyzed by western blot. Results An in vitro cochlear explant model showed that gentamicin caused ROS accumulation in sensory hair cells and induced apoptosis, and this effect was alleviated by pretreatment with ivacaftor. Western blotting showed that ivacaftor administration markedly increased the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO1), and NAD(P)H:quinone oxidoreductase 1 (NQO1). The protective effect of ivacaftor was abolished by the Nrf2 inhibitor ML385. Discussion Our results indicate the protective role of the CFTR-Nrf2-HO1/NQO1 pathway in gentamicin-induced ototoxicity. Ivacaftor may be repositioned or repurposed towards aminoglycosides-induced hearing loss.

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Heme Oxygenase-1 Protects Hair Cells From Gentamicin-Induced Death

Cited by 8 publications

References 45 publications

Norepinephrine protects against cochlear outer hair cell damage and noise-induced hearing loss via α2A-adrenergic receptor

Norepinephrine protects against cochlear outer hair cell damage and noise-induced hearing loss via α2A-adrenergic receptor

Mechanisms and otoprotective strategies of programmed cell death on aminoglycoside-induced ototoxicity

Ivacaftor attenuates gentamicin-induced ototoxicity through the CFTR-Nrf2-HO1/NQO1 pathway

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