Telmisartan Protects Auditory Hair Cells from Gentamicin-Induced Toxicity in vitro.
Cochlea
GW9662
Gentamicin toxicity
Hair cells
Inner ear
Organ of Corti
Peroxisome proliferator-activated receptor γ
Telmisartan
Journal
Audiology & neuro-otology
ISSN: 1421-9700
Titre abrégé: Audiol Neurootol
Pays: Switzerland
ID NLM: 9606930
Informations de publication
Date de publication:
2020
2020
Historique:
received:
25
03
2019
accepted:
13
02
2020
pubmed:
6
5
2020
medline:
22
5
2021
entrez:
6
5
2020
Statut:
ppublish
Résumé
Telmisartan is an angiotensin II receptor blocker that has pleiotropic effects and protective properties in different cell types. Moreover, telmisartan has also shown partial agonism on the peroxisome proliferator-activated receptor γ (PPAR-γ). Auditory hair cells (HCs) express PPAR-γ, and the protective role of PPAR-γ agonists on HCs has been shown. The objective of this study was to investigate the effects of telmisartan on gentamicin-induced ototoxicity in vitro. Cochlear explants were exposed to gentamicin with or without telmisartan, and/or GW9662, an irreversible PPAR-γ antagonist. Telmisartan protected auditory HCs against gentamicin-induced ototoxicity. GW9662 completely blocked this protective effect, suggesting that it was mediated by PPAR-γ signaling. Exposure to GW9662 or telmisartan alone was not toxic to auditory HCs. We found that telmisartan, via PPAR-γ signaling, protects auditory HCs from gentamicin-induced ototoxicity. Therefore, telmisartan could potentially be used in the future to prevent or treat sensorineural hearing loss.
Sections du résumé
BACKGROUND
Telmisartan is an angiotensin II receptor blocker that has pleiotropic effects and protective properties in different cell types. Moreover, telmisartan has also shown partial agonism on the peroxisome proliferator-activated receptor γ (PPAR-γ). Auditory hair cells (HCs) express PPAR-γ, and the protective role of PPAR-γ agonists on HCs has been shown.
OBJECTIVES
The objective of this study was to investigate the effects of telmisartan on gentamicin-induced ototoxicity in vitro.
METHODS
Cochlear explants were exposed to gentamicin with or without telmisartan, and/or GW9662, an irreversible PPAR-γ antagonist.
RESULTS
Telmisartan protected auditory HCs against gentamicin-induced ototoxicity. GW9662 completely blocked this protective effect, suggesting that it was mediated by PPAR-γ signaling. Exposure to GW9662 or telmisartan alone was not toxic to auditory HCs.
CONCLUSIONS
We found that telmisartan, via PPAR-γ signaling, protects auditory HCs from gentamicin-induced ototoxicity. Therefore, telmisartan could potentially be used in the future to prevent or treat sensorineural hearing loss.
Identifiants
pubmed: 32369826
pii: 000506796
doi: 10.1159/000506796
doi:
Substances chimiques
2-chloro-5-nitrobenzanilide
0
Angiotensin II Type 1 Receptor Blockers
0
Anilides
0
Gentamicins
0
PPAR gamma
0
Protective Agents
0
Telmisartan
U5SYW473RQ
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
297-308Informations de copyright
© 2020 The Author(s) Published by S. Karger AG, Basel.