ArticleHearing research2014
Acetaminophen and NAPQI are toxic to auditory cells via oxidative and endoplasmic reticulum stress-dependent pathways.
Article in Hearing research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Impact of nonaspirin nonsteroidal anti-inflammatory agents and acetaminophen on sensorineural hearing loss: a systematic review.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2015Pooled it
- Identification of Reactive Metabolites of Acetaminophen and Saxagliptin in Human Hepatocytes and Hepatic Organoids.Pharmaceutics · 2026Article
- R-α-Lipoic Acid Attenuates Acetaminophen-Induced Acute Liver Injury by Reducing Oxidative Stress, Inflammation, and Mitochondrial Damage in Mice.Drug design, development and therapy · 2026Article
- Multiscale zonation-resolved modeling of dose-dependent determinants of acetaminophen-induced liver injury.Frontiers in pharmacology · 2026Article
- Quinolylnitrone 23 Protects from Auditory Cell Oxidative Injury and Noise-Induced Hearing Loss.ACS pharmacology & translational science · 2025Article
- Underlying mechanisms and treatment of acetaminophen‑induced liver injury (Review).Molecular medicine reports · 2025Review
- Aberrant mitochondrial aggregation of TDP-43 activated mitochondrial unfolded protein response and contributed to recovery of acetaminophen induced acute liver injury.Toxicology research · 2024Article
- Insights into the molecular underlying mechanisms and therapeutic potential of endoplasmic reticulum stress in sensorineural hearing loss.Frontiers in molecular neuroscience · 2024Review
- COX inhibitor use during definitive radiotherapy is associated with worse hearing preservation in patients with vestibular schwannoma.Journal of neuro-oncology · 2023Article
- Geometric Isomer of Guanabenz Confers Hepatoprotection to a Murine Model of Acetaminophen Toxicity.Chemical research in toxicology · 2023Article
- Salubrinal Protects Against Cisplatin-Induced Cochlear Hair Cell Endoplasmic Reticulum Stress by Regulating Eukaryotic Translation Initiation Factor 2α Signalling.Frontiers in molecular neuroscience · 2022Article
- Toxicological Analysis of Hepatocytes Using FLIM Technique: In Vitro versus Ex Vivo Models.Cells · 2021Article
- Autophagy impairment as a key feature for acetaminophen-induced ototoxicity.Cell death & disease · 2021Article
- Glucocorticoids protect HEI-OC1 cells from tunicamycin-induced cell damage via inhibiting endoplasmic reticulum stress.Open life sciences · 2021Article
- The monofunctional platinum(II) compounds, phenanthriplatin and pyriplatin, modulate apoptosis signaling pathways in HEI-OC1 auditory hybridoma cells.Neurotoxicology · 2020Article
- Impact of Endoplasmic Reticulum Stress in Otorhinolaryngologic Diseases.International journal of molecular sciences · 2020Review
- Acetaminophen increases pulmonary and systemic vasomotor tone in the newborn rat.Pediatric research · 2020Article
- Acetaminophen poisoning-induced heart injury: a case-based review.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2019Review
- Expression of drug metabolizing enzymes and transporters in the cochlea: Implications for drug delivery and ototoxicity.Hearing research · 2019Article
- Inactivation of Sirtuin2 protects mice from acetaminophen-induced liver injury: possible involvement of ER stress and S6K1 activation.BMB reports · 2019Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Pain relievers containing N-acetyl-para-aminophenol, also called APAP, acetaminophen or paracetamol, in combination with opioid narcotics are top-selling pharmaceuticals in the U.S. Individuals who abuse these drugs for as little as sixty days can develop tinnitus and progressive bilateral sensorineural hearing loss. Recently published studies indicate that APAP and its metabolic product N-acetyl-p-benzoquinoneimine (NAPQI) are the primary ototoxic agents in this type of pain relievers. However, the mechanisms underlying the deleterious effects of these drugs on auditory cells remain to be fully characterized. In this study, we report cellular, genomic, and proteomic experiments revealing that cytotoxicity by APAP and NAPQI involves two different pathways in Immortomouse-derived HEI-OC1 cells, implicating ROS overproduction, alterations in ER morphology, redistribution of intra-cisternal chaperones, activation of the eIF2α-CHOP pathway, as well as changes in ER stress and protein folding response markers. Thus, both oxidative and ER stress are part of the cellular and molecular mechanisms that contribute to the cytotoxic effects of APAP and NAPQI in these cells. We suggest that these in vitro findings should be taken into consideration when designing pharmacological strategies aimed at preventing the toxic effects of these drugs on the auditory system.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.