Evidence map›Paper›PMID 40512245›Full record

ArticleNeurochemical research2025

Protective Effect of Selegiline (R-deprenyl) in Aminoglycoside-Induced Hearing Loss.

Viktória Humli, Judit Szepesy, Gabriella Zsilla, Ildikó Miklya, Júlia Timár, Szilárd I Szabó, Gábor Polony, Anita Gáborján, György B Halmos, Petra Dunkel and 4 more

Abstract read
In one paragraph

Article in Neurochemical research, 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. Review
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

14 authors.

Viktória HumliDepartment of Oral Biology, Semmelweis University, Budapest, Hungary.
Judit SzepesyDepartment of Oral Biology, Semmelweis University, Budapest, Hungary.
Gabriella ZsillaLaboratory of Molecular Pharmacology, HUN-REN Institute of Experimental Medicine, Budapest, Hungary.
Ildikó MiklyaDepartment of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
Júlia TimárDepartment of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
Szilárd I SzabóLaboratory of Molecular Pharmacology, HUN-REN Institute of Experimental Medicine, Budapest, Hungary.
Gábor PolonyDepartment of Otorhinolaryngology, Head and Neck Surgery, Semmelweis University, Budapest, Hungary.
Anita GáborjánDepartment of Otorhinolaryngology, Head and Neck Surgery, Semmelweis University, Budapest, Hungary.
György B HalmosDepartment of Otorhinolaryngology, Head and Neck Surgery, University of Groningen, Groningen, The Netherlands.
Petra DunkelDepartment of Organic Chemistry, Semmelweis University, Budapest, Hungary.
Péter MátyusDepartment of Organic Chemistry, Semmelweis University, Budapest, Hungary.
Balázs LendvaiPharmacology and Drug Safety Research, Gedeon Richter Plc, Budapest, Hungary.
E Sylvester ViziLaboratory of Molecular Pharmacology, HUN-REN Institute of Experimental Medicine, Budapest, Hungary.
Tibor ZellesDepartment of Oral Biology, Semmelweis University, Budapest, Hungary. zelles.tibor@semmelweis.hu.

Funding

Hungarian-French Collaborative R&I Programme on Biotechnologies TÉT_10-1-2011-0421Hungarian Scientific Research Fund NKFI K128875Ministry of Innovation and Technology of Hungary from the National Research, Development, and Innovation Fund TKP2021-EGA-23
6 · The paper itself

Abstract

Aminoglycoside antibiotics remain indispensable despite their ototoxicity. Like other sensorineural forms, aminoglycoside-induced hearing loss (AGIHL) has no effective pharmacotherapy. Oxidative stress, apoptosis, excitotoxicity and inflammation are key pathological factors of the disease. We hypothesised that selegiline, an irreversible monoamine oxidase-B (MAO-B) inhibitor used in Parkinson's disease, could be repurposed as an otoprotective agent against AGIHL and its effect on dopamine (DA) release from lateral olivocochlear (LOC) fibres, the efferent division of a protective feedback loop plays a major role in the protection against excitotoxicity. Selegiline mitigated AGIHL in BALB/c mice in a dose-dependent manner at different auditory brainstem response frequencies, including 16 kHz, the hearing sensitivity optimum of the animals. It also enhanced the action potential-evoked DA release from LOC efferents in mouse cochlear preparation dose-dependently. Inhibition of DA reuptake contributed to its basic effect of saving DA from metabolism. Among four selegiline analogues tested, the one that increased LOC DA release also provided otoprotection. In contrast, neither safinamide (a reversible MAO-B inhibitor) nor LJP-1207 (a selective semicarbazide-sensitive amine oxidase/vascular-adhesion protein 1 (SSAO/VAP1) inhibitor) prevented AGIHL, despite their antioxidant and anti-inflammatory properties. The reversibility or lack of MAO-B inhibition in safinamide and LJP-1207, respectively, as well as the absence of the propargylamine moiety with known intrinsic neuroprotective activity in both molecules, may explain their ineffectiveness. Selegiline, or certain propargylamine analogues of it, offer a promising therapy against AGIHL by addressing its multifactorial pathology through antioxidant, antiapoptotic, neuroprotective, and anti-inflammatory actions, while enhancing endogenous DAergic protective mechanisms.

Indexed as

AminoglycosidesHearing LossMonoamine Oxidase InhibitorsNeuroprotective AgentsSelegilineAnimalsCochleaDopamineDose-Response Relationship, DrugEvoked Potentials, Auditory, Brain StemMaleMiceMice, Inbred BALB CAminoglycosidesDopamineMonoamine Oxidase InhibitorsNeuroprotective AgentsSelegilineAminoglycoside-induced hearing lossDopamineLOCOtotoxicitySelegilineSNHLs

Identifiers

PMID40512245
PMCPMC12165987

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.