ArticleToxicology mechanisms and methods2016
Hearing, reactive metabolite formation, and oxidative stress in cochleae after a single acute overdose of acetaminophen: an in vivo study.
Article in Toxicology mechanisms and methods, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 11 citations in OpenAlex.
- NAPQI is absent in the mouse brain after sub-hepatotoxic and hepatotoxic doses of acetaminophen.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Expression of drug metabolizing enzymes and transporters in the cochlea: Implications for drug delivery and ototoxicity.Hearing research · 2019Article
- Extrahepatic toxicity of acetaminophen: critical evaluation of the evidence and proposed mechanisms.Journal of clinical and translational research · 2018Review
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4 authors at 1 institution in 1 country.
Funding
Abstract
contextAlthough the liver is the primary target organ in acetaminophen (APAP) toxicity, other organs are affected. Previous data suggested that chronic APAP abuse can be ototoxic and the mechanism involves APAP-induced oxidative stress and reactive metabolite (N-acetyl-p-benzoquinone imine, NAPQI)-induced endoplasmic reticulum stress. However, the effect of a single acute overdose on hearing has not been tested.
objectivesTo determine if a single acute APAP overdose causes hearing damage, and to explore possible mechanisms of APAP ototoxicity. MATERIALS AND
methodsMale C57BL/6 J mice were treated with a single human-relevant overdose of APAP (300 mg APAP per kg bodyweight). Blood, liver and cochleae were harvested at 0, 2, 6 and 24 h post-APAP. In some mice, auditory brainstem responses (ABRs) to a range of frequencies were measured at 24 h. The furosemide plus kanamycin (FS/K) model of drug ototoxicity was used as a positive control for hearing loss. NAPQI formation after APAP was assessed by measuring glutathione depletion and covalent protein binding, and oxidative stress was assessed by measuring glutathione disulfide.
resultsThere was no evidence of reactive metabolite formation or hearing loss after a single overdose of APAP at a clinically relevant dose. However, there was a transient increase in oxidative stress. DISCUSSION: Although a single acute overdose was not ototoxic, there was evidence of oxidative stress which may support a role for oxidative stress in hearing loss due to chronic APAP abuse.
conclusionA single human-relevant acute overdose of APAP causes transient oxidative stress in cochleae but not hearing loss.
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