Evidence map›Paper›PMID 40724969›Full record

ArticleInternational journal of molecular sciences2025

Molecular Mechanisms of Aminoglycoside-Induced Ototoxicity in Murine Auditory Cells: Implications for Otoprotective Drug Development.

Cheng-Yu Hsieh, Jia-Ni Lin, Yi-Fan Chou, Chuan-Jen Hsu, Peir-Rong Chen, Yu-Hsuan Wen, Chen-Chi Wu, Chuan-Hung Sun

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Cheng-Yu HsiehDepartment of Otolaryngology, Head and Neck Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427213, Taiwan.ORCID 0000-0002-2588-8881
Jia-Ni LinDepartment of Otolaryngology, Head and Neck Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427213, Taiwan.
Yi-Fan ChouDepartment of Otolaryngology, Head and Neck Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427213, Taiwan.ORCID 0000-0002-9932-7091
Chuan-Jen HsuDepartment of Otolaryngology, Head and Neck Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427213, Taiwan.
Peir-Rong ChenSchool of Medicine, Tzu Chi University, Hualien 970374, Taiwan.
Yu-Hsuan WenSchool of Medicine, Tzu Chi University, Hualien 970374, Taiwan.
Chen-Chi WuInstitute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan.ORCID 0000-0002-5047-2204
Chuan-Hung SunDepartment of Otolaryngology, Head and Neck Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427213, Taiwan.ORCID 0000-0002-5133-7725

Funding

Buddhist Tzu Chi Medical Foundation TTCRD 113-04Minister of Science and Technology in Taiwan NSTC-113-2314-B-303-005
6 · The paper itself

Abstract

Aminoglycoside antibiotics are critical in clinical use for treating severe infections, but they can occasionally cause irreversible sensorineural hearing loss. To establish a rational pathway for otoprotectant discovery, we provide an integrated, three-tier methodology-comprising cell-model selection, transcriptomic analysis, and a gentamicin-Texas Red (GTTR) uptake assay-to guide the development of otoprotective strategies. We first utilized two murine auditory cell lines-UB/OC-2 and HEI-OC1. We focused on TMC1 and OCT2 and further explored the underlying mechanisms of ototoxicity. UB/OC-2 exhibited a higher sensitivity to gentamicin, which correlated with elevated OCT2 expression confirmed via RT-PCR and Western blot. Transcriptomic analysis revealed upregulation of PI3K-Akt, calcium, and GPCR-related stress pathways in gentamicin-treated HEI-OC1 cells. Protein-level analysis further confirmed that gentamicin suppressed phosphorylated Akt while upregulating ER stress markers (GRP78, CHOP) and apoptotic proteins (cleaved caspase 3, PARP). Co-treatment with PI3K inhibitors (LY294002, wortmannin) further suppressed Akt phosphorylation, supporting the role of PI3K-Akt signaling in auditory cells. To visualize drug entry, we used GTTR to evaluate its applicability as a fluorescence-based uptake assay in these cell lines, which were previously employed mainly in cochlear explants. Sodium thiosulfate (STS) and

Indexed as

AminoglycosidesAnti-Bacterial AgentsHair Cells, AuditoryOtotoxicityProtective AgentsAnimalsCell LineEndoplasmic Reticulum Chaperone BiPEndoplasmic Reticulum StressGentamicinsMicePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionAminoglycosidesAnti-Bacterial AgentsEndoplasmic Reticulum Chaperone BiPGentamicinsHspa5 protein, mousePhosphatidylinositol 3-KinasesProtective AgentsProto-Oncogene Proteins c-aktaminoglycosidesmouse auditory cell linesototoxicitytranscriptomic analysis

Identifiers

PMID40724969
PMCPMC12295342

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Registered trials

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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.