ArticleScience translational medicine2015
Endotoxemia-mediated inflammation potentiates aminoglycoside-induced ototoxicity.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype.Clinical pharmacology and therapeutics · 2022Guideline
- Review
- Disentangling neuroimmune landscapes across peripheral activation paradigms resolves divergent glial state programs.Research square · 2026Article
- Pharmacologic Inhibition of JAK1/2 Potentiates Aminoglycoside-Induced Ototoxicity.Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology · 2026Article
- Endothelial miR-7052 Safeguards Blood-Brain Barrier Integrity During Endotoxemia by Co-repressing ANGPT2 and PDE5A.Molecular neurobiology · 2026Article
- Mechanisms, prevention, and management of aminoglycoside-induced hearing loss in neonates and children: a translational review.Frontiers in pharmacology · 2026Review
- Hair cell loss - cause or consequence of hearing loss?Frontiers in cell and developmental biology · 2026Review
- Characterization of exosome-mediated propagation of systemic inflammatory responses into the central nervous system.Molecular brain · 2024Article
- Piplartine attenuates aminoglycoside-induced TRPV1 activity and protects from hearing loss in mice.Science translational medicine · 2024Article
- Characterization of exosome-mediated propagation of systemic inflammatory responses into the Central Nervous System.Research square · 2024Article
- Sound conditioning strategy promoting paracellular permeability of the blood-labyrinth-barrier benefits inner ear drug delivery.Bioengineering & translational medicine · 2024Article
- Otoprotection against aminoglycoside- and cisplatin-induced ototoxicity focusing on the upstream drug uptake pathway.Journal of the Chinese Medical Association : JCMA · 2024Review
- Molecular Characteristics of Cisplatin-Induced Ototoxicity and Therapeutic Interventions.International journal of molecular sciences · 2023Review
- Mechanisms and Impact of Aminoglycoside-Induced Vestibular Deficits.American journal of audiology · 2023Review
- Aminoglycosides-Related Ototoxicity: Mechanisms, Risk Factors, and Prevention in Pediatric Patients.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Human blood-labyrinth barrier model to study the effects of cytokines and inflammation.Frontiers in molecular neuroscience · 2023Article
- Mechanisms and otoprotective strategies of programmed cell death on aminoglycoside-induced ototoxicity.Frontiers in cell and developmental biology · 2023Review
- Local Delivery of Therapeutics to the Cochlea Using Nanoparticles and Other Biomaterials.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Effects of Combined Gentamicin and Furosemide Treatment on Cochlear Macrophages.International journal of molecular sciences · 2022Article
- Identifying targets to prevent aminoglycoside ototoxicity.Molecular and cellular neurosciences · 2022Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The ototoxic aminoglycoside antibiotics are essential to treat severe bacterial infections, particularly in neonatal intensive care units. Using a bacterial lipopolysaccharide (LPS) experimental model of sepsis, we tested whether LPS-mediated inflammation potentiates cochlear uptake of aminoglycosides and permanent hearing loss in mice. Using confocal microscopy and enzyme-linked immunosorbent assays, we found that low-dose LPS (endotoxemia) greatly increased cochlear concentrations of aminoglycosides and resulted in vasodilation of cochlear capillaries without inducing paracellular flux across the blood-labyrinth barrier (BLB) or elevating serum concentrations of the drug. Additionally, endotoxemia increased expression of both serum and cochlear inflammatory markers. These LPS-induced changes, classically mediated by Toll-like receptor 4 (TLR4), were attenuated in TLR4-hyporesponsive mice. Multiday dosing with aminoglycosides during chronic endotoxemia induced greater hearing threshold shifts and sensory cell loss compared to mice without endotoxemia. Thus, endotoxemia-mediated inflammation enhanced aminoglycoside trafficking across the BLB and potentiated aminoglycoside-induced ototoxicity. These data indicate that patients with severe infections are at greater risk of aminoglycoside-induced hearing loss than previously recognized.
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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.