Protective effects of esomeprazole against cisplatin-induced ototoxicity: an in vitro and in vivo study.
Aquat Toxicol
; 260: 106573, 2023 Jul.
Article
em En
| MEDLINE
| ID: mdl-37210931
ABSTRACT
In this study, we aimed to identify novel compounds that could afford protection against cisplatin-induced ototoxicity by employing both cell- and zebrafish (Danio rerio)-based screening platforms. We screened 923 US Food and Drug Administration-approved drugs to identify potential compounds exhibiting protective effects against cisplatin-induced ototoxicity in HEI-OC1 cells (auditory hair cell line). The screening strategy identified esomeprazole and dexlansoprazole as the primary hit compounds. Subsequently, we examined the effects of these compounds on cell viability and apoptosis. Our results revealed that esomeprazole and dexlansoprazole inhibited organic cation transporter 2 (OCT2), thus providing in vitro evidence that these compounds could ameliorate cisplatin-induced ototoxicity by directly inhibiting OCT2-mediated cisplatin transport. In vivo, the protective effects were validated using zebrafish; esomeprazole was found to decrease cisplatin-induced hair cell damage in neuromasts. Furthermore, the esomeprazole-treated group showed a significantly lower number of TUNEL-positive cells than the cisplatin-treated group. Collectively, our findings revealed that esomeprazole exerts a protective effect against cisplatin-induced hair cell damage in both HEI-OC1 cells and a zebrafish model.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Poluentes Químicos da Água
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Ototoxicidade
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article