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Protective Effects of (-)-Butaclamol Against Gentamicin-Induced Ototoxicity: In Vivo and In Vitro Approaches
Protective Effects of (-)-Butaclamol Against Gentamicin-Induced Ototoxicity: In Vivo and In Vitro Approaches
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Protective Effects of (-)-Butaclamol Against Gentamicin-Induced Ototoxicity: In Vivo and In Vitro Approaches
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Protective Effects of (-)-Butaclamol Against Gentamicin-Induced Ototoxicity: In Vivo and In Vitro Approaches
Protective Effects of (-)-Butaclamol Against Gentamicin-Induced Ototoxicity: In Vivo and In Vitro Approaches

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Protective Effects of (-)-Butaclamol Against Gentamicin-Induced Ototoxicity: In Vivo and In Vitro Approaches
Protective Effects of (-)-Butaclamol Against Gentamicin-Induced Ototoxicity: In Vivo and In Vitro Approaches
Journal Article

Protective Effects of (-)-Butaclamol Against Gentamicin-Induced Ototoxicity: In Vivo and In Vitro Approaches

2025
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Overview
Gentamicin-induced ototoxicity leads to irreversible sensorineural hearing loss due to structural and functional damage to inner ear hair cells. In this study, we identified (-)-butaclamol as a potent protective agent against gentamicin-induced cytotoxicity through high-content screening (HCS) of a natural compound library. (-)-Butaclamol significantly enhanced cell viability in both HEI-OC1 cells and zebrafish neuromasts, demonstrating robust protection against gentamicin toxicity. Mechanistically, (-)-butaclamol inhibited intrinsic apoptosis, as evidenced by reduced TUNEL-positive cell counts and the downregulation of BAX and caspase-3, alongside the upregulation of BCL-2. Moreover, (-)-butaclamol activated key survival signaling pathways, including AKT/mTOR and ERK, while suppressing the inflammatory regulator NF-κB. Additional analyses revealed that (-)-butaclamol effectively mitigated oxidative stress and restored autophagic activity, as confirmed by CellROX and LysoTracker assays. Notably, TMRE staining showed that (-)-butaclamol preserved mitochondrial membrane potential in zebrafish hair cells, indicating mitochondrial protection. Collectively, these findings suggest that (-)-butaclamol exerts comprehensive cytoprotective effects against gentamicin-induced ototoxicity by modulating apoptosis, enhancing survival signaling, and restoring mitochondrial and cellular homeostasis. These results highlight the therapeutic potential of (-)-butaclamol and provide a foundation for future studies aimed at its clinical application.

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