ArticleCell death & disease2021
Autophagy impairment as a key feature for acetaminophen-induced ototoxicity.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Adipose-Derived Mesenchymal Stem Cell Exosomes Attenuate Oxygen-Glucose Deprivation-Induced Cochlear Damage by Inducing Autophagy-Associated Signaling.International journal of molecular sciences · 2026Article
- Targeting Autophagy for Otoprotection: Translating Basic Mechanisms into Clinical Strategies.International journal of molecular sciences · 2026Review
- Autophagy in Sensorineural Hearing Loss: Jekyll or Hyde?International journal of molecular sciences · 2026Review
- Bioactive hydrogels for the reconstruction of sensorineural hearing loss.Bioactive materials · 2026Review
- Precise subcellular organelle-targeted analyses of hepatotoxicity ofChinese herbal medicines · 2026Article
- CpG-oligodeoxynucleotides challenged macrophages ameliorate acetaminophen induced liver injury by activating TLR9/IRG1/itaconate metabolic pathway.Molecular medicine (Cambridge, Mass.) · 2025Article
- Article
- Cdh23 Gene Mutation-Induced Vestibular Dysfunction in Mice: Abnormal Stereocilia Bundle and Otolith Development and Activation of p53/FoxO Signaling Pathway.Journal of molecular neuroscience : MN · 2025Article
- Ototoxicity of polystyrene nanoplastics in mice, HEI-OC1 cells and zebrafish.Frontiers in molecular neuroscience · 2024Article
- Autophagy increase in Merosin-Deficient Congenital Muscular Dystrophy type 1A.European journal of translational myology · 2023Article
- Degranulation of Murine Resident Cochlear Mast Cells: A Possible Factor Contributing to Cisplatin-Induced Ototoxicity and Neurotoxicity.International journal of molecular sciences · 2023Article
- Expression of miR-210-3p in the aqueous humor of patients with age-related cataracts and its effect on human lens epithelial cell injury induced by hydrogen peroxide.Arquivos brasileiros de oftalmologia · 2023Article
- Ferroptosis is involved in PGPS-induced otitis media in C57BL/6 mice.Cell death discovery · 2022Article
- The role of autophagy and ferroptosis in sensorineural hearing loss.Frontiers in neuroscience · 2022Review
- Cellular autophagy, the compelling roles in hearing function and dysfunction.Frontiers in cellular neuroscience · 2022Review
- Article
- Detecting Novel Ototoxins and Potentiation of Ototoxicity by Disease Settings.Frontiers in neurology · 2021Review
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
Macroautophagy/autophagy is a highly conserved self-digestion pathway that plays an important role in cytoprotection under stress conditions. Autophagy is involved in hepatotoxicity induced by acetaminophen (APAP) in experimental animals and in humans. APAP also causes ototoxicity. However, the role of autophagy in APAP-induced auditory hair cell damage is unclear. In the present study, we investigated autophagy mechanisms during APAP-induced cell death in a mouse auditory cell line (HEI-OC1) and mouse cochlear explant culture. We found that the expression of LC3-II protein and autophagic structures was increased in APAP-treated HEI-OC1 cells; however, the degradation of SQSTM1/p62 protein, the yellow puncta of mRFP-GFP-LC3 fluorescence, and the activity of lysosomal enzymes decreased in APAP-treated HEI-OC1 cells. The degradation of p62 protein and the expression of lysosomal enzymes also decreased in APAP-treated mouse cochlear explants. These data indicate that APAP treatment compromises autophagic degradation and causes lysosomal dysfunction. We suggest that lysosomal dysfunction may be directly responsible for APAP-induced autophagy impairment. Treatment with antioxidant N-acetylcysteine (NAC) partially alleviated APAP-induced autophagy impairment and apoptotic cell death, suggesting the involvement of oxidative stress in APAP-induced autophagy impairment. Inhibition of autophagy by knocking down of Atg5 and Atg7 aggravated APAP-induced ER and oxidative stress and increased apoptotic cell death. This study provides a better understanding of the mechanism responsible for APAP ototoxicity, which is important for future exploration of treatment strategies for the prevention of hearing loss caused by ototoxic medications.
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Registered trials
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