ArticleNeurotoxicity research2013
Salicylate selectively kills cochlear spiral ganglion neurons by paradoxically up-regulating superoxide.
Article in Neurotoxicity research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 45 citations in OpenAlex.
- Aspirin in Audiology: A Dual-Edged Sword in Hearing Loss and Its Nanotechnology-Driven Future.Drug design, development and therapy · 2026Review
- GPRASP2 deficiency contributes to apoptosis in the spiral ganglion cells via the AMPK/DRP1 signaling pathway.Heliyon · 2024Article
- Considering the protective effect of exendin-4 against oxidative stress in spiral ganglion neurons.Iranian journal of basic medical sciences · 2023Article
- Protective Effect of Resveratrol in an Experimental Model of Salicylate-Induced Tinnitus.International journal of molecular sciences · 2022Article
- Neuroprotective Effect of Valproic Acid on Salicylate-Induced Tinnitus.International journal of molecular sciences · 2021Article
- Protective Effect of Curcumin against Sodium Salicylate-Induced Oxidative Kidney Damage, Nuclear Factor-Kappa Dysregulation, and Apoptotic Consequences in Rats.Antioxidants (Basel, Switzerland) · 2021Article
- Antioxidative stress-induced damage in cochlear explants.Journal of otology · 2020Article
- Some Ototoxic Drugs Destroy Cochlear Support Cells Before Damaging Sensory Hair Cells.Neurotoxicity research · 2020Article
- Salicylate-Induced Ototoxicity of Spiral Ganglion Neurons: CaNeurotoxicity research · 2019Article
- Sodium salicylate alters temporal integration measured through increasing stimulus presentation rates.International journal of audiology · 2019Article
- Article
- Paraquat initially damages cochlear support cells leading to anoikis-like hair cell death.Hearing research · 2018Article
- Effects of the cannabinoid CBHearing research · 2017Article
- Kanamycin Damages Early Postnatal, but Not Adult Spiral Ganglion Neurons.Neurotoxicity research · 2017Article
- Plastic changes along auditory pathway during salicylate-induced ototoxicity: Hyperactivity and CF shifts.Hearing research · 2017Article
- Can Animal Models Contribute to Understanding Tinnitus Heterogeneity in Humans?Frontiers in aging neuroscience · 2016Review
- Cobalt-Induced Ototoxicity in Rat Postnatal Cochlear Organotypic Cultures.Neurotoxicity research · 2015Article
- Tinnitus: animal models and findings in humans.Cell and tissue research · 2015Review
- Review of salicylate-induced hearing loss, neurotoxicity, tinnitus and neuropathophysiology.Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Aspirin and its active ingredient salicylate are potent antioxidants that have been reported to be neuro- and otoprotective. However, when consumed in large quantities, these drugs can cause temporary hearing loss and tinnitus. Moreover, recent studies indicate that after several days of treatment, salicylate selectively destroys the spiral ganglion neurons and auditory nerve fibers that relay sounds from the sensory hair cells to the brain. Why salicylate selectively damages spiral ganglion neurons while sparing the hair cells and supports cells is unclear. Here we show that high dose of salicylate trigger an apoptotic response in spiral ganglion neurons characterized morphologically by soma shrinkage and nuclear condensation and fragmentation plus activation of extrinsic initiator caspase-8 and intrinsic initiator caspase-9 several days after the onset of drug treatment. Salicylate treatment triggered an upsurge in the toxic superoxide radical only in spiral ganglion neurons, but not in neighboring hair cells and support cells. Mn TMPyP pentachloride, a cell permeable scavenger of superoxide blocked the expression of superoxide staining in spiral ganglion neurons and almost completely blocked the damage to the nerve fibers and spiral ganglion neurons. NMDA receptor activation is known to increase neuronal superoxide levels. Since NMDA receptors are mainly found on spiral ganglion neurons and since salicylate enhances NMDA receptor currents, the selective killing of spiral ganglion neurons is likely a consequence of enhanced and sustained activation of NMDA receptors by salicylate.
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Registered trials
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