ArticleScientific reports2017
Autophagic flux, a possible mechanism for delayed gentamicin-induced ototoxicity.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Caloric Restriction Mimetic Hydroxycitrate Mitigates Acute Nephrotoxicity via Autophagy Activation and Oxidative Stress Reduction.Biomolecules · 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
- Molecular remodeling of the central auditory pathway in tinnitus revealed by RNA sequencing.Genes & genomics · 2026Article
- Mechanisms, prevention, and management of aminoglycoside-induced hearing loss in neonates and children: a translational review.Frontiers in pharmacology · 2026Review
- An In Vitro Oxidative Stress Model of the Human Inner Ear Using Human-Induced Pluripotent Stem Cell-Derived Otic Progenitor Cells.Antioxidants (Basel, Switzerland) · 2024Article
- A Low Dose of Rapamycin Promotes Hair Cell Differentiation by Enriching SOX2Journal of the Association for Research in Otolaryngology : JARO · 2024Article
- Article
- Re-telling the story of aminoglycoside ototoxicity: tales from sub-Saharan Africa.Frontiers in neurology · 2024Article
- Abnormal Cholesterol Metabolism and Lysosomal Dysfunction Induce Age-Related Hearing Loss by Inhibiting mTORC1-TFEB-Dependent Autophagy.International journal of molecular sciences · 2023Article
- The cochlea is built to last a lifetime.Hearing research · 2023Review
- RIPOR2-mediated autophagy dysfunction is critical for aminoglycoside-induced hearing loss.Developmental cell · 2022Article
- A Review on Peripheral Tinnitus, Causes, and Treatments from the Perspective of Autophagy.Experimental neurobiology · 2022Review
- Pravastatin Administration Alleviates Kanamycin-Induced Cochlear Injury and Hearing Loss.International journal of molecular sciences · 2022Article
- Analysis of potential protective effects of caffeic acid phenethyl ester against gentamicin ototoxicity: An experimental study.Iranian journal of basic medical sciences · 2022Article
- Cellular autophagy, the compelling roles in hearing function and dysfunction.Frontiers in cellular neuroscience · 2022Review
- mTOR Signaling in the Inner Ear as Potential Target to Treat Hearing Loss.International journal of molecular sciences · 2021Review
- Autophagy impairment as a key feature for acetaminophen-induced ototoxicity.Cell death & disease · 2021Article
- Icariin Treatment Protects Against Gentamicin-Induced Ototoxicity via Activation of the AMPK-SIRT3 Pathway.Frontiers in pharmacology · 2021Article
- A Screen of Autophagy Compounds Implicates the Proteasome in Mammalian Aminoglycoside-Induced Hair Cell Damage.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aminoglycoside antibiotics including gentamicin (GM) induce delayed ototoxic effects such as hearing loss after long-term use, unlike the early-onset ototoxicity caused by cisplatin. The purpose of the study was to identify the mechanism of the delayed GM-induced ototoxicity by exploring the role of autophagy in vitro and in vivo. Treating HEI-OC1 auditory cells with GM led to a time-dependent increase of the autophagosome marker LC3-II, which was accompanied by cell death. In contrast, cisplatin and penicillin caused a rapid increase and had no effect on LC3-II levels, respectively. LC3-II-expressing autophagosomes co-localized with the labeled GM. GM-treated autophagosomes expressed reduced levels of Rab7, which is necessary for the fusion of autophagosomes with lysosomes. When the autophagic flux enhancer rapamycin was applied to GM-treated cells, Rab7 and the lysosomal enzyme cathepsin D were upregulated, and increased cell survival was observed. In animal studies, the intraperitoneal injection of GM worsened hearing thresholds and induced the accumulation of LC3 in the organ of Corti. This hearing impairment was attenuated by rapamycin. These findings suggest that the delayed onset-ototoxicity of GM may be closely related to the accumulation of autophagosomes via impaired autophagy. This GM-induced auditory cell death could be inhibited by enhancing autophagic flux.
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