Products Cited in Publications Worldwide 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

Hong, Sumin; Han, Eunjung; Park, Saemi; Hyun, Kyungtae; Lee, Yunkyoung; Baek, Hyun woo; Kim, Hwee-Jin; Rah, Yoon Chan; Choi, June

DOI:

Abstract

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 , as evidenced by reduced TUNEL-positive cell counts and the downregulation of BAX and caspase-3, alongside the upregulation of . Moreover, (-)-butaclamol activated key survival signaling pathways, including AKT/mTOR and , while suppressing the inflammatory regulator . Additional analyses revealed that (-)-butaclamol effectively mitigated oxidative stress and restored autophagic activity, as confirmed by CellROX and LysoTracker assays. Notably, 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 , 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.

Keywords

(-)-butaclamol ; in vitro ; in vivo ; ototoxicity ; gentamicin ; hair cell

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